piperidines and Dementia

Topics: Cholinesterase Inhibitors; Dementia; Humans; Piperidines

Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the impact of perfusion modifiers should be evaluated.. In this systematic review, the impact of acute and chronic intake of four acetylcholinesterase inhibitors (AChEIs) on cerebral perfusion in adults was investigated: physostigmine, donepezil, galantamine, and rivastigmine.. Chronic AChEI treatment results in an increase of cerebral perfusion in treatment-responsive patients with Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia in the frontal, parietal, temporal, and occipital lobes, as well as the cingulate gyrus. These effects appear to be temporary, dose-related, and consistent across populations and different AChEI types. On the contrary, further perfusion decline was reported in patients not receiving AChEIs or not responding to the treatment.. AChEIs appear to be a potential perfusion modifier in neurodegenerative patients. More research focused on quantitative perfusion in both patients with and without a cholinergic deficit is needed to draw conclusions on whether AChEI intake should be considered when analyzing perfusion data.

Topics: Acetylcholinesterase; Alzheimer Disease; Cerebrovascular Circulation; Cholinesterase Inhibitors; Cognition; Dementia; Galantamine; Humans; Indans; Parkinson Disease; Perfusion; Phenylcarbamates; Piperidines; Rivastigmine

Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.

Topics: Dementia; Hallucinations; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Urea

Insomnia and hypersomnia are conditions with multifactorial causes that can be difficult to treat. There have been recent developments and changes in the treatment of both conditions, including the addition of some agents that have a novel mechanism of action. This review summarizes recent changes and highlights pertinent updates.. Benzodiazepine receptor agonists received a warning in 2019 regarding the possibility of complex sleep behaviors, such as sleepwalking. Zolpidem has been marketed in new dosage forms that include sublingual tablets and oral spray formulations. Orexin receptor antagonists appear to be well tolerated with a good safety profile. Suvorexant received an approval for the treatment of patients with comorbid insomnia and dementia. Lemborexant was demonstrated to be effective for maintenance insomnia. Trazodone was shown to affect the oligomerization of tau proteins thus suggesting potential implications in attenuating dementia pathology. Pitolisant, a novel histamine-3 receptor antagonist/inverse agonist, gained approval for the treatment of excessive daytime sleepiness in adults with narcolepsy as well as obstructive sleep apnea. Solriamfetol, a new norepinephrine and dopamine reuptake inhibitor, was approved for hypersomnolence based on good efficacy, but with cardiovascular warnings.. Recent advancements in the treatment of insomnia includes agents with novel mechanisms, new indications, and new dosage forms. Risk of complex sleep behaviors, and possible next-day driving impairment, should be discussed for all agents used for insomnia, including orexin receptor antagonists. Novel agents also are available for hypersomnia and there are options beyond traditional stimulants that may have great utility.

Topics: Azepines; Carbamates; Dementia; Disorders of Excessive Somnolence; GABA-A Receptor Agonists; Humans; Orexin Receptor Antagonists; Phenylalanine; Piperidines; Pyridines; Pyrimidines; Sleep Aids, Pharmaceutical; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders; Trazodone; Triazoles; Zolpidem

Donepezil is the most commonly used cholinesterase inhibitor. The indication for its use is Alzheimer's disease. A number of clinical studies have shown its effectiveness in vascular dementia, dementia with Lewy bodies, Parkinson's disease with dementia, dementia due to traumatic brain injury. It is shown that dementia is a risk factor for falls, and standard measures to prevent falls in the elderly are ineffective in patients with cognitive impairment. This article provides a review of publications on the influence of donepezil on gait and balance. Most authors agree that donepezil is able to improve some parameters of gait, such as gait velocity and stride time variability, which can increase stability and reduce the risk of falls. The effect of donepezil on motor function is small, but its use may be particularly valuable if other approaches to treatment of gait disorders in patients with cognitive impairment are ineffective.. Донепезил - одним из наиболее часто используемых ингибиторов холинэстеразы. Показанием для его назначения является болезнь Альцгеймера. В ряде клинических исследований показана его эффективность и при сосудистой деменции, деменции с тельцами Леви, болезни Паркинсона с деменцией, деменции вследствие черепно-мозговой травмы. Известно, что наличие деменции является фактором риска падений, при этом стандартные меры по предотвращению падений у пожилых часто оказываются неэффективными у пациентов с когнитивными нарушениями. В статье представлен обзор публикаций, посвященных влиянию донепезила на ходьбу и равновесие. Большинство авторов сходятся во мнении, что донепезил способен улучшать некоторые параметры ходьбы, такие как скорость ходьбы и вариабельность продолжительности шага, что может повышать устойчивость и снижать риск падений. Эффект донепезила на двигательные функции невелик, однако его использование может быть особенно ценным при неэффективности других подходов к коррекции нарушений ходьбы у пациентов с когнитивными нарушениями.

Topics: Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Gait; Gait Disorders, Neurologic; Humans; Indans; Piperidines

Psychosis is common across dementia types with a prevalence of 20% to 70%. Currently, no pharmacologic treatment is approved for dementia-related psychosis. Atypical antipsychotics are frequently used to treat these disorders, despite significant safety concerns. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Patients in the pimavanserin group experienced a significant (p=0.001) improvement in Scale for the Assessment of Positive Symptoms - Parkinson's disease (SAPS-PD) scores vs. placebo. In a subgroup analysis of patients with cognitive impairment (MMSE score ≥21 but ≤24), the observed improvement on the SAPS-PD with pimavanserin (N=50) was also significant (p=0.002) and larger than in the overall study population without an adverse effect on cognition. In a Phase 2 study with pimavanserin in Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS). In a prespecified subgroup of patients with a baseline NPI-NH PS ≥12, a substantively larger treatment effect (p=0.011) was observed vs. participants with NPI-NH PS <12. The results of these studies in cognitively impaired patients with PDP provided the scientific foundation for an ongoing study of pimavanserin for treating patients with dementia-related psychosis associated with the most common neurodegenerative disorders. The study uses a relapse-prevention design with the endpoint of time-to-relapse of psychosis to evaluate the long-term efficacy and safety of pimavanserin as a potential treatment for hallucinations and delusions of dementia-related psychosis.

Topics: Alzheimer Disease; Clinical Trials as Topic; Dementia; Humans; Mental Status and Dementia Tests; Parkinson Disease; Piperidines; Psychotic Disorders; Serotonin 5-HT2 Receptor Antagonists; Severity of Illness Index; Treatment Outcome; Urea

The prevalence of Alzheimer's disease (AD) continues to rise, while treatment options for cognitive impairment are limited. Acetylcholinesterase inhibitors (AChEIs) aim to provide symptomatic benefit for cognitive decline, however these drugs are not without adverse events (AEs). The safety profile of each drug must be taken carefully into consideration before being prescribed, as new dosages and formulations have recently been approved. Areas covered: Donepezil, galantamine and rivastigmine are the three AChEIs approved for the treatment of varying stages of AD. Numerous clinical trials and post-marketing studies have evaluated the safety of these medications. This article will review the safety, efficacy and tolerability of these drugs in treating AD. Topics including pharmacovigilance databases, concomitant drug interactions, prescribing cascades, and treatment discontinuation are also covered. Expert opinion: AChEI use in those with mild, moderate or severe AD provide modest improvements in cognition, function and behavior. The pharmacological treatment of AD using AChEIs is associated with generally mild AEs. Differences in drug formulations should be taken into account when determining the most appropriate route of administration for each individual. Furthermore, discontinuation of AChEIs must be carefully monitored as it may be associated with worsening cognitive impairment.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Drug Interactions; Galantamine; Humans; Indans; Piperidines; Rivastigmine; Severity of Illness Index

With the ever-growing geriatric population, research on brain diseases such as dementia is more imperative now than ever. The most prevalent of all dementias is Alzheimer's disease, a progressive neurodegenerative disease that presents with deficits in memory, cognition, motor skills, and a general decline in the quality of life. The social and economic burden associated with Alzheimer's disease is tremendous and is projected to grow even greater over the coming years. There is a specific need to elucidate and improve the treatments available, not only to alleviate the symptoms related to dementias such as Alzheimer's but also to prevent the formation of the disease. This is an effort that can be expedited and made more efficient by utilizing an animal model such as the zebrafish. This paper reviews the utility of zebrafish in Alzheimer's research by examining research on a sampling of the treatments available for the disease, specifically donepezil, memantine, and methylene blue. The human model and the shortcomings of the rodent model are also discussed.

Topics: Alzheimer Disease; Animals; Dementia; Disease Models, Animal; Donepezil; Humans; Indans; Memantine; Methylene Blue; Piperidines; Rodentia; Species Specificity; Zebrafish

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders encountered in clinical practice. Whilst dementia has long been synonymous with AD, it is becoming more widely accepted as part of the clinical spectrum in PD (PDD). Neuropsychiatric complications, including psychosis, mood and anxiety disorders, and sleep disorders also frequently co-exist with cognitive dysfunctions in AD and PDD patients. The incidence of such symptoms is often a significant source of disability, and may aggravate pre-existing cognitive deficits. Management of AD and PDD involves both pharmacological and non-pharmacological measures. Although research on pharmacological therapies for AD and PDD has so far had some success in terms of developing symptomatic treatments, the benefits are often marginal and non-sustained. These shortcomings have led to the investigation of non-pharmacological and novel treatments for both AD and PD. Furthermore, in light of the diverse constellation of other neuropsychiatric, physical, and behavioural symptoms that often occur in AD and PD, consideration needs to be given to the potential side effects of pharmacological treatments where improving one symptom may lead to the worsening of another, rendering the clinical management of these patients challenging. Therefore, the present article will critically review the evidence for both pharmacological and non-pharmacological treatments for cognitive impairment in AD and PD patients. Treatment options for other concomitant neuropsychiatric and behavioural symptoms, as well as novel treatment strategies will also be discussed.

Topics: Alzheimer Disease; Animals; Antiparkinson Agents; Cholinesterase Inhibitors; Cognitive Behavioral Therapy; Dementia; Donepezil; Excitatory Amino Acid Antagonists; Exercise Therapy; Galantamine; Humans; Indans; Memantine; Parkinson Disease; Piperidines; Rivastigmine; Sleep Wake Disorders; Treatment Outcome

Dopamine depletion is one of the most important features of Parkinson's Disease (PD). However, insufficient response to dopaminergic replacement therapy suggests the involvement of other neurotransmitter systems in the pathophysiology of PD. Cholinergic degeneration contributes to gait impairments, cognitive impairment, psychosis, and REM-sleep disturbances, among other symptoms. Areas covered: In this review, we explore the idea that enhancing cholinergic tone by pharmacological or neurosurgical procedures could be a first-line therapeutic strategy for the treatment of symptoms derived from cholinergic degeneration in PD. Expert opinion: Rivastigmine, a drug that increases cholinergic tone by inhibiting the enzyme cholinesterase, is effective for dementia, whereas the use of Donepezil is still in the realm of investigation. Interesting results suggest the efficacy of these drugs in the treatment of gait dysfunction. Evidence on the clinical effects of these drugs for psychosis and REM-sleep disturbances is still weak. Stimulation of the pedunculo-pontine tegmental nuclei (which provide cholinergic innervation to the brain stem and subcortical nuclei) has also been used with some success for the treatment of gait dysfunction. Anticholinergic drugs should be used with caution in PD, as they may aggravate cholinergic symptoms. Notwithstanding, in some patients they might help control parkinsonian motor symptoms.

Topics: Animals; Cholinergic Agents; Cholinergic Neurons; Clinical Trials as Topic; Cognition Disorders; Dementia; Donepezil; Gait; Humans; Indans; Nerve Degeneration; Parkinson Disease; Piperidines; Psychotic Disorders

Cholinesterase enzymes metabolize acetylcholine (ACh). Inhibition of acetylcholinesterase (AChE) in damaged but functional cholinergic synapses in the brains of dementia patients increases intrasynaptic ACh. This enhances cholinergic neurotransmission and improves cognition. There is a window of opportunity for this symptomatic treatment effect that opens and closes during the course of dementia depending on when significant synaptic damage occurs. Cholinesterases also metabolize extrasynaptic ACh with butyrylcholinesterase (BuChE) apparently playing the major dynamic role in extracellular ACh homeostasis. Extracellular ACh plays a key regulatory role in controlling the reactivity and functional states of non-excitable cells, such as neuroglia. Current inhibitors of cholinesterases (ChEIs) have similar effects on intrasynaptic ACh, but differ markedly in abilities to upregulate extracellular AChE, inhibit BuChE, and influence the fibrilization of amyloid-β peptides. Importantly, ChEIs can have detrimental disease modifying effects in particular individuals characterized by age, gender, and genotype. In contrast, preliminary evidence suggests that the right dose of the right ChEI in the right patient might significantly slow the progression of neurodegenerative processes. For a particular patient, understanding the condition of cholinergic synapses and the reactivity and functional status of neuroglia could allow administration of appropriate ChEI therapy for symptomatic and disease modifying benefits.

Topics: Acetylcholine; Acetylcholinesterase; Amyloid beta-Peptides; Apolipoproteins E; Butyrylcholinesterase; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Indans; Microglia; Phenylcarbamates; Piperidines; Rivastigmine

The cultural arts have gained attention for their potential to generate social and behavioral changes in people with dementia. Although individual cultural arts intervention studies have reported positive outcomes, most are excluded from systematic reviews because of methodological weakness. We reviewed findings from 27 systematic and integrative reviews of pharmacologic, psychosocial, and cultural arts interventions to identify promising outcomes as well as limitations in current approaches. Although results point to the potential success of interventions tailored to individual interests, most focused on limited measurements of individual change. In moving forward, cultural arts intervention research must not be limited to the tools of the clinical trial model. Instead, researchers should carefully rethink what constitutes rigorous and effective research for interventions aimed at creating a meaningful personal experience for the participant rather than measurable change.

Topics: Art Therapy; Dementia; Donepezil; Humans; Indans; Piperidines

Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cholinesterase Inhibitors; Cognitive Dysfunction; Dementia; Disease Progression; Donepezil; Education, Medical, Continuing; Galantamine; Humans; Indans; Lewy Body Disease; Nootropic Agents; Peptide Fragments; Phenylcarbamates; Piperidines; Positron-Emission Tomography; Reference Standards; Rivastigmine; tau Proteins; Tomography, Emission-Computed, Single-Photon

Charles Bonnet syndrome (CBS) is characterized by recurrent or persistent complex visual hallucinations that occur in visually impaired individuals with intact cognition and no evidence of psychiatric illness. Patients usually retain insight into the unreal nature of their hallucinations.3,4 CBS is often misdiagnosed, and predominantly affects elderly patients with vision changes (e.g., age-related macular degeneration, glaucoma, and cataract). While many require only the assurance of the benign nature of the hallucinations, nonpharmacological and pharmacological interventions have been reported to be useful in the treatment of CBS. This case involves an 83-year-old female, with a two-year history of CBS, who presented to the clinic with worsening visual hallucinations over the past few months. She was starting to lose insight into her hallucinations secondary to her new diagnosis of dementia. Several pharmacological agents were explored to determine the most appropriate choice for our patient. Ultimately, this patient was started on donepezil (reported to be successful in a CBS case report), which helped improve her cognitive function. At future follow-up visits, her hallucinations improved and her cognitive function stabilized. Pharmacists should be aware of CBS and its treatment options to properly assist physicians in the medication-selection process to alleviate distress experienced by patients with CBS. In patients who may benefit from pharmacological treatment, physicians should weigh the risks and benefits of the different treatment options. Donepezil can be a favorable option in CBS patients with Alzheimer's type dementia.

Topics: Aged, 80 and over; Cognition; Dementia; Donepezil; Female; Hallucinations; Humans; Indans; Nootropic Agents; Piperidines; Syndrome; Treatment Outcome; Vision Disorders

At present, there may be over 210,000 people with Down syndrome (DS) over the age of 55 in the United States (US) who have significant needs for augmented services due to circumstances related to ordinary and/or pathological aging. From 1979 through 2003, the birth prevalence of DS rose from 9.0 to 11.8 (31.1%) per 10,000 live births in 10 representative US regions. This increase, largely due to women conceiving after age 35, portends an ever-growing population of people with DS who may be subject to pathogenic aging. Whereas Trisomy 21 is one of the most widespread genetic causes of intellectual disability (ID), it still is one of the least understood of all genetic ID syndromes. While longevity in people with DS has improved appreciably in as modest a period as 30 years, age-specific risk for mortality still is considerably increased compared both with other people with ID or with the typically developing population. The penetrance of the phenotype is widely distributed, even though a consistent genotype is assumed in 95% of the cases. Some, but not all body systems, exhibit signs of premature or accelerated aging. This may be due to both genetic and epigenetic inheritance. We now know that the long-term outcome for people with DS is not as ominous as once contemplated; a number of people with DS are living into their late 60s and 70s with few if any major signs of pathogenic aging. Alzheimer's disease (AD), a devastating disease that robs a person of their memory, abilities and personality, is particularly common in elder adults with DS, but is not a certainty as originally thought, some 20% to 30% of elder adults with DS might never show any, or at most mild signs of AD. DS has been called a mature well-understood syndrome, not in need of further research or science funding. We are only beginning to understand how epigenetics affects the phenotype and it may be feasible in the future to alter the phenotype through epigenetic interventions. This chapter is divided into two sections. The first section will review typical and atypical aging patterns in somatic issues in elder adults with DS; the second section will review the multifaceted relationship between AD and DS.

Topics: Adult; Aging; Alzheimer Disease; Amyloid beta-Peptides; Cholinesterase Inhibitors; Dementia; Donepezil; Down Syndrome; Female; Humans; Incidence; Indans; Intellectual Disability; Male; Metabolic Syndrome; Middle Aged; Nootropic Agents; Oxidative Stress; Peptide Fragments; Phenotype; Piperidines; Prevalence; Telomere Shortening; Treatment Outcome; United States

Mixed dementia is caused by the combination of several simultaneous pathological processes, e.g., Alzheimer's disease and cerebrovascular pathology, Alzheimer's disease and dementia with Lewy bodies, cerebrovascular pathology and dementia with Lewy bodies etc. Many authors consider mixed dementia as the most frequent form of dementia in elderly people. Cholinesterase inhibitors, along with the modulator of glutamate receptors memantine, are commonly used for treatment of different types of dementia, in particular, Alzheimer's disease. Controlled studies have shown their effect in the treatment of dementia with Lewy bodies and vascular dementia. However, there are limited data on the efficacy and safety of the new antidementia drugs in treatment of mixed dementia. In this article, the approaches to the diagnosis of mixed dementia and possibilities of its treatment with cholinesterase inhibitors (donepezil) are described.

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Indans; Piperidines; Treatment Outcome

The drugs currently available for the treatment of Alzheimer's disease and other dementias can provide limited symptomatic improvement. The acetylcholinesterase inhibitors donepezil, rivastigmine, and galantamine and the NMDA-receptor antagonist memantine have produced modest but apparently persistent improvements in cognition, activities of daily living, and behavior in patients with disease severity ranging from mild to severe. Among the acetylcholinesterase inhibitors, transdermal rivastigmine causes fewer gastrointestinal side effects than the oral formulation. Whether adding memantine to an acetylcholinesterase inhibitor is more effective than an acetylcholinesterase inhibitor alone remains to be established; clinical trial results have been mixed. None of these agents have been shown to stop or reverse the underlying neurodegenerative process.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Excitatory Amino Acid Antagonists; Galantamine; Humans; Indans; Memantine; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate; Rivastigmine

Randomized controlled trials (RCTs) provide safety and efficacy data for regulatory approval of antidementia drugs, but offer limited data regarding real-world effectiveness. Long-term observational controlled studies (LTOCs) extend our understanding by providing longitudinal data across multiple stages of Alzheimer's disease (AD).. Comparisons of strengths, limitations, evidence level, and results for monotherapy (cholinesterase inhibitors) and combination therapy (cholinesterase inhibitors + memantine) in RCTs versus LTOCs were made.. Similar to RCTs, LTOCs have shown that both monotherapy and combination therapy are associated with slower cognitive and functional decline. Combination therapy is associated with better cognitive outcomes and greater delays in time to nursing home admission versus monotherapy or no treatment. Persistent antidementia drug treatment is associated with slower decline in cognition, daily function, and global severity, even in patients with advanced disease.. LTOCs provide complementary evidence regarding effectiveness of antidementia therapy over many years, a time course relevant to AD management. These findings also provide compelling arguments in favor of using LTOCs to estimate effectiveness, risk-benefit, and costs of AD treatments.

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Dopamine Agents; Evidence-Based Medicine; Humans; Indans; Memantine; Nootropic Agents; Piperidines; Prevalence; Randomized Controlled Trials as Topic

Donepezil is a reversible, non-competitive piperidine-type acetylcholinesterase inhibitor (AChEI) that is structurally unique compared with other currently available AChEIs. It was developed as a symptomatic treatment to compensate for the progressive loss of cholinergic signal between neurons, a consequence of neuronal cell loss in the brains of patients with Alzheimer's disease (AD). Clinical trials conducted over the 15 years since the drug was first licensed and available for use in patients with mild to moderate AD (1997) have shown that donepezil is efficacious and well tolerated at all stages of AD, from patients with mild or moderate impairment to those with severe disease. The published literature contains nearly 2000 papers on donepezil, and more than 200 of these articles relate to randomized controlled clinical trials. Trials in patients with mild cognitive impairment (MCI) failed to meet all of their primary objectives, but provided insights into patient selection and the design of trials. Overall, more than a decade of donepezil research has gradually changed attitudes toward therapy of AD from a general belief that no clinically useful treatment exists to the present day understanding that symptomatic therapy may be effective across the spectrum of dementia stages.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Indans; Nootropic Agents; Piperidines

Previous Cochrane reviews have considered the use of cholinesterase inhibitors in both Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). The clinical features of DLB and PDD have much in common and are distinguished primarily on the basis of whether or not parkinsonism precedes dementia by more than a year. Patients with both conditions have particularly severe deficits in cortical levels of the neurotransmitter acetylcholine. Therefore, blocking its breakdown using cholinesterase inhibitors may lead to clinical improvement.. To assess the efficacy, safety and tolerability of cholinesterase inhibitors in dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), and cognitive impairment in Parkinson's disease falling short of dementia (CIND-PD) (considered as separate phenomena and also grouped together as Lewy body disease).. The trials were identified from a search of ALOIS, the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group (on 30 August 2011) using the search terms Lewy, Parkinson, PDD, DLB, LBD. This register consists of records from major healthcare databases (MEDLINE, EMBASE, PsycINFO, CINAHL) and many ongoing trial databases and is updated regularly.Reference lists of relevant studies were searched for additional trials.. Randomised, double-blind, placebo-controlled trials assessing the efficacy of treatment with cholinesterase inhibitors in DLB, PDD and cognitive impairment in Parkinson's disease (CIND-PD).. Data were extracted from published reports by one review author (MR). The data for each 'condition' (that is DLB, PDD or CIND-PD) were considered separately and, where possible, also pooled together. Statistical analysis was conducted using Review Manager version 5.0.. Six trials met the inclusion criteria for this review, in which a total of 1236 participants were randomised. Four of the trials were of a parallel group design and two cross-over trials were included. Four of the trials included participants with a diagnosis of Parkinson's disease with dementia (Aarsland 2002a; Dubois 2007; Emre 2004; Ravina 2005), of which Dubois 2007 remains unpublished. Leroi 2004 included patients with cognitive impairment and Parkinson's disease (both with and without dementia). Patients with dementia with Lewy bodies (DLB) were included in only one of the trials (McKeith 2000).For global assessment, three trials comparing cholinesterase inhibitor treatment to placebo in PDD (Aarsland 2002a; Emre 2004; Ravina 2005) reported a difference in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) score of -0.38, favouring the cholinesterase inhibitors (95% CI -0.56 to -0.24, P < 0.0001).For cognitive function, a pooled estimate of the effect of cholinesterase inhibitors on cognitive function measures was consistent with the presence of a therapeutic benefit (standardised mean difference (SMD) -0.34, 95% CI -0.46 to -0.23, P < 0.00001). There was evidence of a positive effect of cholinesterase inhibitors on the Mini-Mental State Examination (MMSE) in patients with PDD (WMD 1.09, 95% CI 0.45 to 1.73, P = 0.0008) and in the single PDD and CIND-PD trial (WMD 1.05, 95% CI 0.42 to 1.68, P = 0.01) but not in the single DLB trial.For behavioural disturbance, analysis of the pooled continuous data relating to behavioural disturbance rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.36 to -0.04, P = 0.01).For activities of daily living, combined data for the ADCS and the Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.38 to -0.02, P = 0.03).For safety and tolerability, those taking a cholinesterase inhibitor were more likely to experience an adverse event (318/452 versus 668/842; odds ratio (OR) 1.64, 95% CI 1.26 to 2.15, P = 0.0003) and to drop out (128/465 versus 45/279; OR 1.94, 95% CI 1.33 to 2.84, P = 0.0006). Adverse events were more common amongst those taking rivastigmine (357/421 versus 173/240; OR 2.28, 95% CI 1.53 to 3.38, P < 0.0001) but not those taking donepezil (311/421 versus 145/212; OR 1.24, 95% CI 0.86 to 1.80, P = 0.25). Parkinsonian symptoms. The currently available evidence supports the use of cholinesterase inhibitors in patients with PDD, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales. The effect in DLB remains unclear. There is no current disaggregated evidence to support their use in CIND-PD.

Topics: Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Humans; Indans; Lewy Body Disease; Neuroprotective Agents; Parkinson Disease; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine

Research into Gingko biloba extract EGb 761® has been ongoing for many years. Early studies showed that the extract was superior to placebo in improving symptoms of dementia, and this has been confirmed by more recent research. The GINDEM-NP, GOTADAY and GOT-IT! studies showed that 240 mg/day EGb 761® improved cognitive function, neuropsychiatric symptoms, activities of daily living, and quality of life in patients with mild to moderate dementia compared with placebo, with results reproducible in independent trials. The strength of the effect in terms of improvements in neurosensory symptoms associated with old age and dementia was strong enough to be detected by caregivers and independent clinicians. A combination of 240 mg/day EGb 761® and 10 mg/day (initially 5 mg/day) donepezil was also more effective than either drug alone. Regarding the improvement of neuropsychiatric symptoms, a cross-comparison of studies with different antidementia agents suggests that EGb 761® is at least as effective as memantine, galantamine, and donepezil. Safety data revealed no important safety concerns with EGb 761®.

Topics: Activities of Daily Living; Cognition; Dementia; Donepezil; Drug Therapy, Combination; Ginkgo biloba; Humans; Indans; Nootropic Agents; Phytotherapy; Piperidines; Plant Extracts; Quality of Life

The term 'dementia' encompasses a number of neurodegenerative diseases of which Alzheimer's disease (AD) is the most common. Prior to 2003, cholinesterase inhibitors, such as donezepil, were the only class of drugs approved to treat mild-to-moderate AD. In 2003, memantine became the first drug approved by the US FDA to treat moderate-to-severe AD. Currently, both memantine and donepezil are FDA approved for the treatment of moderate-to-severe AD. This article examines the pharmacologic profile of memantine, evidence for memantine's efficacy in moderate-to-severe AD and other dementias, its novel use in other neuropsychiatric disorders and future implications and research directions for memantine.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Dopamine Agents; Humans; Indans; Memantine; Neurodegenerative Diseases; Piperidines

Alzheimer's dementia represents organ failure of the brain. It denotes a clinical milestone that is the result of a pathological process, Alzheimer's disease (AD), which over 1 or more decades has wrought insidious destruction, and finally overwhelmed the brain's capacities to compensate. It is incurable, progressive, and follows an individual pace and course. AD is particularly demanding and devastating to family and caregivers, and patients, all of whom suffer psychologically and emotionally. The cholinesterase inhibitors (ChEIs) donepezil, galantamine, and rivastigmine and the N-methyl- D-aspartate receptor antagonist memantine are approved by the US Food and Drug Administration for AD; they are often used in combination once the disease reaches moderate stages. The relatively good safety profile of these medications, along with their efficacy in alleviating symptoms, is supported by several level-I evidence-grade, short-term, randomized, placebo-controlled trials (RCTs). However, these studies are of limited value in assessing the real-world clinical and economic impact of AD therapies. Long-term, observational studies can provide complementary information to results from short-term clinical trials and more accurately assess practical long-term benefits, risks, costs, and effects on clinically meaningful end points. There is now accumulating and convergent evidence from short- and long-term RCTs, longer-term open-label extensions of RCTs, and long-term observational studies that ChEIs and memantine reduce decline in cognition and daily function, and delay nursing home placement. Optimal care in AD is multifactorial; it includes early diagnosis and multidisciplinary care with educational and nonpharmacological interventions, while ensuring safety, treating comorbidities, caring for caregivers, and appropriate initiation and maintenance of combination therapy.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Cognition; Dementia; Disease Progression; Donepezil; Galantamine; Humans; Indans; Memantine; Nootropic Agents; Phenylcarbamates; Piperidines; Rivastigmine; Tacrine; Time Factors; Treatment Outcome

Dementia associated with Parkinson's disease (PDD) is a common problem and one that is associated with significant morbidity and mortality. Over the past decade, increasing research efforts and funding have been directed toward an improved understanding of PDD. Despite these efforts, fundamental gaps remain in our knowledge. Consequently, therapeutic progress has been frustratingly slow and incomplete. To significantly affect PDD, novel "disease-modifying" agents, rather than more traditional neurotransmitter replacement approaches, likely will be required.

Topics: Cholinesterase Inhibitors; Clinical Trials as Topic; Dementia; Diagnosis, Differential; Humans; Parkinson Disease; Piperidines; Urea

The first part of the present review describes the current status of elderly people with behavioral and psychological symptoms of dementia (BPSD) in the community and basic viewpoints for differentiating between different forms of dementia. Specifically, it focuses on four points among the data and research related to determining the current status of elderly people with BPSD. We also propose basic concepts for differentiating between the core symptoms of dementia and BPSD, BPSD and delirium, and agitation and delirium. In the second part of the present review, various aspects of the symptom 'agitation' are discussed based on the experience of our home visit medical service for people with dementia by describing two cases. In cases such as Case 1, where the subject was given high doses of antipsychotics, we believe the problem was that the physicians immediately abstracted all of the abnormal behavior in the subject's life as 'agitation', and provided treatment to the subject accordingly. In Case 2, where the subject had dementia with Lewy bodies (DLB), we propose that it is crucial to differentiate clearly between agitation and delirium. Both of these cases show the risks of focusing treatment simply on agitation. When BPSD occurs in a person with dementia, the burden on caregivers increases. At such times, physicians tend to side with the family rather than with the patient. However, medical care is intended to be for the afflicted person, and physicians should base their plans for medical intervention on this principle.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Caregivers; Delirium; Dementia; Diagnosis, Differential; Donepezil; Home Care Services; House Calls; Humans; Indans; Lewy Body Disease; Male; Nootropic Agents; Piperidines; Psychomotor Agitation; Tokyo

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are the two most common types of dementing neurodegenerative disease after Alzheimer's disease (AD). Both of these conditions are often diagnosed late or not at all.. Selective literature review.. The severe cholinergic and dopaminergic deficits that are present in both DLB and PDD produce not only motor manifestations, but also cognitive deficits, mainly in the executive and visual-constructive areas, as well as psychotic manifestations such as visual hallucinations, delusions, and agitation. The intensity of these manifestations can fluctuate markedly over the course of the day, particularly in DLB. Useful tests for differential diagnosis include magnetic resonance imaging and electroencephalography; in case of clinical uncertainty, nuclear medical procedures and cerebrospinal fluid analysis can be helpful as well. Neuropathological studies have revealed progressive alpha-synuclein aggregation in affected areas of the brain. In DLB, beta-amyloid abnormalities are often seen as well.. DLB should be included in the differential diagnosis of early dementia. If motor manifestations arise within one year (DLB), dopaminergic treatment should be initiated. On the other hand, patients with Parkinson's disease should undergo early screening for signs of dementia so that further diagnostic and therapeutic steps can be taken in timely fashion, as indicated. Cholinesterase inhibitors are useful for the treatment of cognitive deficits and experiential/behavioral disturbances in both DLB (off-label indication) and PDD (approved indication).

Topics: Aged; Brain; Cholinesterase Inhibitors; Cross-Sectional Studies; Dementia; Diagnosis, Differential; Diagnostic Imaging; Donepezil; Early Diagnosis; Humans; Indans; Lewy Body Disease; Mental Disorders; Neuropsychological Tests; Parkinson Disease; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine

Alzheimer's disease is the most common form of dementia seen in the clinical practice. The principal risk factor is aging. There is not currently any available curative medication. However, there a family of drugs call the cholinesterase inhibitors (donepezile, galantamine and rivastigmine) the enhances cholinergic activity in the CNS. Also, memantine is available is a NMDA receptor modulator. A new transdermal way of administration is available now for rivastigmine. The rivastigmines patches are now a rational alternative focusing in getting more tolerance, better blood levels of the drug and compliance to treatment in Alzheimer's disease patients.

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Galantamine; Humans; Indans; Phenylcarbamates; Piperidines; Rivastigmine

Dementia and depression are serious causes of global impairment in the elderly. This review is aimed at finding pharmacological reports from 2007-2008 so as to examine whether new guidance is available to treat these patients.. Studies on Alzheimer's disease and Lewy body dementias show that cholinesterase inhibitors are still first line treatment for these diseases and memantine is indicated in moderate/severe Alzheimer's disease, whereas there is as yet no standard available treatment for frontotemporal dementias. Treatment of depression in the elderly shows the same results as in younger individuals, and cerebrovascular pathology is important for treatment resistance.. There is a need for new drugs that focus on treatment resistant and nonresponder individuals. Most studies are confirmation of previous reported results.

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Therapy; Evidence-Based Medicine; Geriatric Psychiatry; Humans; Indans; Lewy Body Disease; Parkinson Disease; Piperidines

Some randomized studies, mostly of short duration, have indicated that cholinesterase inhibitors (donepezil, rivastigmine and galantamine) may have a beneficial effect in Alzheimer's disease, vascular dementia and in dementia caused by Lewy body disease. The benefit of these drugs in clinical practice has not been satisfactorily documented.. Literature collected regularly for many years supplemented by extensive non-systematic searches of Pubmed and Embase.. Only in a few placebo-controlled, double-blind, randomised studies were the patients followed for more than one year. Several clinical tests were performed, among them the Mini Mental Status (MMS)-test, which is the most commonly used test in clinical practice. The three cholinesterase inhibitors led to statistically significant results, although of limited clinical relevance, in various forms of dementia.. Based on the results obtained it could be questioned whether the observed effects are of clinical significance. Only a small proportion of patients with Alzheimer's disease seem to benefit from the cholinesterase inhibitors tested, and it is difficult to predict who will in advance. Treatment should first be evaluated after 2-4 months and subsequently on a regular basis, and accepted clinical tests should be applied.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Dementia, Vascular; Donepezil; Evidence-Based Medicine; Galantamine; Humans; Indans; Lewy Body Disease; Phenylcarbamates; Piperidines; Rivastigmine; Time Factors; Treatment Outcome

The effectiveness of the 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear.. To review the evidence for the effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and the neuropeptide-modifying agent memantine in achieving clinically relevant improvements, primarily in cognition, global function, behavior, and quality of life, for patients with dementia.. Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006.. English-language randomized, controlled trials were included in the review if they evaluated pharmacologic agents for adults with a diagnosis of dementia, did not use a crossover design, and had a quality score of at least 3 on the Jadad scale.. Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate.. 96 publications representing 59 unique studies were eligible for this review. Both cholinesterase inhibitors and memantine had consistent effects in the domains of cognition and global assessment, but summary estimates showed small effect sizes. Outcomes in the domains of behavior and quality of life were evaluated less frequently and showed less consistent effects. Most studies were of short duration (6 months), which limited their ability to detect delay in onset or progression of dementia. Three studies directly compared different cholinesterase inhibitors and found no differences in cognition and behavior.. Limitations of available studies included short duration, inclusion of only patients with mild to moderate Alzheimer disease, poor reporting of adverse events, lack of clear definitions for statistical significance, limited evaluation of behavior and quality-of-life outcomes, and limited direct comparison of different treatments.. Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia.

Topics: Activities of Daily Living; Affect; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Excitatory Amino Acid Antagonists; Galantamine; Humans; Indans; Memantine; Phenylcarbamates; Piperidines; Quality of Life; Rivastigmine; Tacrine

The efficacy of acetylcholinesterase (AChE) inhibitors for the treatment of dementia diseases has been established for both key cognitive symptoms and dementia-associated symptoms such as aggressiveness and the ability to perform activities of daily life. Presently three AChE inhibitors are approved for the treatment of mild to moderately severe Alzheimer dementia: donepezil, rivastigmine and galantamine. Rivastigmine is also approved for the treatment of Parkinson's dementia. The three substances differ in their efficacy and their pharmacological properties. AChE inhibitors should be used for long-term treatment. The clinical course should be monitored every six months.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Clinical Trials as Topic; Dementia; Donepezil; Galantamine; Humans; Indans; Lewy Body Disease; Multicenter Studies as Topic; Neuroprotective Agents; Nootropic Agents; Parkinson Disease; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine; Time Factors

Diabetes mellitus and cognitive decline are major public health concerns among the elderly. In diabetic subjects without dementia, certain cognitive domains are impaired, such as memory, attention, and executive/frontal lobe function (diabetic cognitive dysfunction). Recent epidemiological studies have suggested that diabetes increases the risks for vascular dementia as well as Alzheimer's disease. There are accumulating evidences that indicate biological linkage between impaired brain glucose metabolism homeostasis and cognitive decline. Diabetes may cause serious brain damages through several mechanisms and induce a variety of cognitive decline. Most critical issue to be resolved is to identify the mechanism of dementia leading from diabetic cognitive dysfunction. Once elderly diabetics had severe cognitive decline, effective treatment of diabetes were hardly obtained. Thus, diabetic cognitive decline should be considered as an important comorbidity of the elderly diabetes and long-term management of hyperglycemia is required from a view point to sustain healthy brain function. In this short review, we are summarizing the clinical features and current biological findings of diabetic cognitive decline. Also, we introduce the comprehensive treatment of demented diabetic elderly, including therapeutic strategy, nursing and care.

Topics: Aged; Antihypertensive Agents; Brain; Cognition Disorders; Dementia; Diabetes Mellitus, Type 2; Donepezil; Glucose; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Hyperlipidemias; Hypertension; Indans; Piperidines; Risk; Risk Factors

Treatments for the symptomatic relief of Alzheimer's disease are available but despite advances in our ability to treat persons with various forms of dementia, more effective treatments are needed. The cholinesterase inhibitors donepezil, rivastigmine, and galantamine have demonstrated efficacy in improving cognition and global status and to a lesser extent, behavioral abnormalities relative to placebo in patients with mild-to-moderate Alzheimer's disease. Rivastigmine has been shown to benefit patients with dementia with Lewy Bodies and with dementia associated with Parkinson's disease. Donepezil and galantamine have also been shown to be mildly effective in dementia due to cerebral ischemia. Memantine has a distinct mechanism of action and is effective in moderate-to-severe AD. The benefits from these drugs, however, are limited and their long-term effectiveness has not been well-demonstrated. Their clinical utility is controversial. Many novel approaches that promise to provide more effective treatments are currently being pursued.

Topics: Acetylcholine; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Galantamine; Humans; Indans; Lewy Body Disease; Neurodegenerative Diseases; Neuroprotective Agents; Parkinson Disease; Phenylcarbamates; Piperidines; Rivastigmine; Tacrine

Mild cognitive impairment (MCI) is a clinical syndrome thought to represent the transition between normal function and dementia. This review describes data that support the existence of such a transitional phase, outlines the heterogeneity of MCI and how that has influenced the evolving concept of MCI, and discusses the impact of heterogeneity on recent MCI clinical trials.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Clinical Trials as Topic; Cognition Disorders; Dementia; Donepezil; Humans; Indans; Models, Psychological; Neuropsychological Tests; Piperidines; Syndrome; Terminology as Topic; Treatment Outcome

Topics: Alzheimer Disease; Dementia; Donepezil; Estrogen Replacement Therapy; Humans; Indans; Magnetic Resonance Imaging; Mental Status Schedule; Nootropic Agents; Piperidines; Positron-Emission Tomography; Randomized Controlled Trials as Topic; Risk Factors; Sensitivity and Specificity

Dementia associated with probable Alzheimer's disease (AD) is one of the most common types of dementia. Patients with AD often have cholinergic deficits in association with the disease. The cholinesterase inhibitors donepezil hydrochloride, galantamine hydrobromide, and rivastigmine tartrate are the current mainstays of symptomatic treatment for patients with AD. In clinical trials for all three agents, beneficial effects on standard measures of cognitive and global function have been observed in patients with mild to moderate AD. Although none of the cholinesterase inhibitors has been approved for treatment of patients in advanced stages of AD, all three agents have had beneficial cognitive effects among patients with less severe forms of the disease. The author provides information on recommended dosing for all three medications, noting that cholinesterase inhibitors must be titrated carefully. When administered with caution, galantamine, rivastigmine, and donepezil are generally well-tolerated pharmacologic treatment options. The author notes that, after patients and their caregivers understand that no change in status is considered an "improvement" and a desirable clinical outcome for patients with AD, if no benefits are achieved with the use of one cholinesterase inhibitor, switching to another medication in this class might be beneficial. The author further suggests that the benefits found in cholinesterase inhibitors for patients with AD might also be applicable to patients with other types of dementia such as vascular dementia and dementia with Lewy bodies as cholinergic deficits have been reported in association with these types of dementia as well.

Topics: Acetylcholine; Acetylcholinesterase; Aged; Alzheimer Disease; Cholinesterase Inhibitors; Cost of Illness; Dementia; Donepezil; Galantamine; Humans; Indans; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine; Severity of Illness Index

Defining the regions of the brain displaying the neuropathological lesions that cause Alzheimer's disease (AD) will facilitate deeper investigation into their pathophysiology. In addition, this would allow the effects of AD treatment to be specifically monitored in those regions. Cognitive decline in AD begins with failings of episodic memory and spatial orientation in patients with very mild AD. Clinical and experimental data show that the brain regions primarily involved in memory impairment early in AD are the hippocampus and the medial temporal lobe. Is it possible to prevent the development of pathophysiology in these regions? The neuroprotective effect of cholinesterase inhibitors has been demonstrated in a number of different models, including protection of cortical neurons in models of oxygen-glucose deprivation and glutamate-induced toxicity, and protection against the effects of hippocampal mitochondrial dysfunction in transgenic mouse models of AD. These preclinical data are supported by extensive clinical data indicating that maximum benefit is gained through early initiation of treatment with donepezil and suggest that the benefits afforded by donepezil may extend beyond those of a purely symptomatic treatment.

Topics: Aged; Alzheimer Disease; Brain; Cholinergic Agents; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Hypoxia, Brain; Indans; Nervous System; Piperidines

Today drug therapy of dementia in elderly patients is possible. Owing to a huge increase in the number of elderly people throughout the Western world in the coming years, evidence-based treatment of dementia in this group is needed. The article reviews double-blind, randomized trials on the effect in dementia of donepezil, galantamine, rivastigmine and memantine up to 2003. A total of 27 studies were included. Donepezil, galantamine, rivastigmine and memantine improve cognition and the global level of functioning in mild to moderate Alzheimer's disease (AD). Most evidence exists for donepezil and galantamine. The effect of rivastigmine is best documented in Lewy body dementia (LB). Galantamine, memantine and donepezil may improve cognition in vascular dementia (VD). Galantamine may improve behavioural psychological symptoms of dementia (BPSD). No solid evidence for drug therapy in severe dementia exists. Elderly patients with mild to moderate AD should be offered drug therapy. One should also consider expanding the indication of dementia treatment to LB and VD. An international consensus on what primary efficacy variables to use is needed.

Topics: Aged; Alzheimer Disease; Dementia; Donepezil; Galantamine; Humans; Indans; Memantine; Neuroprotective Agents; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine

Topics: Alzheimer Disease; Benzodiazepines; Dementia; Donepezil; Galantamine; Ginkgo biloba; Humans; Indans; Memantine; Nootropic Agents; Olanzapine; Phenylcarbamates; Physostigmine; Phytotherapy; Piperidines; Rivastigmine; Selegiline; Tacrine

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Dementia; Diagnosis, Differential; Donepezil; Female; Humans; Indans; Limbic System; Male; Neurofibrillary Tangles; Piperidines

To evaluate the representation of frail older adults in randomized controlled trials (RCTs), and to assess consequences of under representation by analyzing drug discontinuation rates.. A cohort of older adults newly dispensed donepezil in Ontario between September 2001 and March 2002 was constructed using administrative data. A systematic review of the literature identified RCTs of donepezil. Patients dispensed donepezil were then compared to clinical trial subjects. Discontinuation rates were examined for patients with and without potential contraindications to this drug.. There were 6,424 older adults in the Ontario cohort with new claims for donepezil. Ten RCTs evaluating the use of donepezil were identified (n = 3,423). Between 51% and 78% of the Ontario cohort would have been ineligible for RCT enrollment. Patients dispensed donepezil were older (80.3 vs. 73.7 years, p < 0.001) and more likely to be in long-term care (14.1 vs. 7.1%, p < 0.001) than RCT subjects. Overall, 27.8% of the Ontario cohort discontinued donepezil within seven months of initial prescription. Discontinuation rates were significantly higher for patients with a history of obstructive lung disease, active cardiovascular disease, or Parkinsonism.. Fewer than half of the older adults dispensed donepezil in Ontario would have been eligible to participate in the RCTs that established the efficacy of this drug. Discontinuation rates were higher among patient groups not represented in the trials. Clinicians should carefully assess the potential risks and benefits of such drug therapies for older patients with dementia.

Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Cohort Studies; Dementia; Donepezil; Female; Humans; Indans; Male; Middle Aged; Ontario; Patient Dropouts; Patient Selection; Piperidines; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition; Dementia; Donepezil; Galantamine; Ginkgo biloba; Haloperidol; Humans; Indans; Memantine; Olanzapine; Phenylcarbamates; Physostigmine; Phytotherapy; Piperidines; Risperidone; Rivastigmine; Selegiline; Tacrine; Vitamin E

Alzheimer's disease is common, incurable and disabling. It is expected to grow dramatically in prevalence over the next 50 years. At current, the standard of care for patients with mild and moderately severe Alzheimer's disease includes the use of acetylcholinesterase inhibitors. Donepezil (Aricept) is a highly selective acetylcholinesterase inhibitors with a pharmacokinetic profile allowing once-daily dosing. There is an extensive knowledge base derived from published clinical trials of donepezil in Alzheimer's disease, revealing consistent efficacy in cognition, global clinical ratings and daily function. Donepezil is also associated with additional meaningful outcomes such as reduced risk for, or delay to, nursing home placement. Despite a sense of limited efficacy of this drug class among prescribers, number needed-to-treat analyses suggest donepezil is highly effective at reducing the long-term adverse outcomes associated with Alzheimer's disease.

Topics: Alzheimer Disease; Anorexia; Cholinesterase Inhibitors; Clinical Trials as Topic; Cognition Disorders; Dementia; Diarrhea; Donepezil; Drug Interactions; Humans; Indans; Nausea; Piperidines; Treatment Outcome; Vomiting

Topics: Alzheimer Disease; Dementia; Donepezil; Galantamine; Ginkgo biloba; Humans; Indans; Memantine; Nootropic Agents; Phenylcarbamates; Physostigmine; Phytotherapy; Piperidines; Rivastigmine; Tacrine

In recent years, the efficacy of symptomatic treatment in patients with Alzheimer's disease has repeatedly been demonstrated in a number of multicenter studies. Such treatment aims both to improve the patient's cognitive abilities and to preserve his or her quality of life and ability to cope with the activities of daily life. In this way the burden on relatives and caregivers is reduced, and the need for home or institutionalized care delayed. Causally effective therapeutic strategies resulting in a cure or the delaying of pathophysiological progression are currently not available, but are being investigated in ongoing clinical and experimental studies. Presently available treatments should be initiated early on, and applied as long as needed, which requires the earliest possible clinical diagnosis by the primary-care physician. The results of initial studies reveal an effect of antidementia agents also in mixed Alzheimer's and vascular dementia, as well as vascular and lewy-body dementia. Efforts to obtain approval for these indications are underway.

Topics: Activities of Daily Living; Alzheimer Disease; Carbamates; Cholinesterase Inhibitors; Controlled Clinical Trials as Topic; Dementia; Dementia, Vascular; Donepezil; Dopamine Agents; Female; Galantamine; Ginkgo biloba; Humans; Indans; Male; Memantine; Meta-Analysis as Topic; Multicenter Studies as Topic; Neuroprotective Agents; Nootropic Agents; Phenylcarbamates; Phytotherapy; Piperidines; Placebos; Plant Preparations; Prospective Studies; Rivastigmine; Tacrine; Time Factors

Multiple behavioural and psychological symptoms of dementia (BPSD) are commonly associated with all dementia subtypes, and worsen during disease progression. BPSD arise due to impairment of cholinergic function in the cortex, hippocampus and related limbic systems. Recent studies have investigated the effect of cholinesterase inhibitors on BPSD. The dual acetylcholinesterase/butyrylcholinesterase (AChE/BuChE) inhibitor rivastigmine was shown to have several potential advantages over the AChE-selective inhibitors donepezil and galantamine for the treatment of BPSD. Rivastigmine appears to be effective across the range of dementia severity from mild to severe, and across the spectrum of dementia (Alzheimer's disease [AD], the AD variant with Lewy bodies, Parkinson's disease dementia and vascular dementia subtypes). It also appears to have a disease-modifying potential. Rivastigmine improved a wider range of behavioural symptoms (apathy, anxiety/depression, hallucinations and delusions) than donepezil and galantamine (which improved apathy and depression/anxiety only). Unlike donepezil, rivastigmine reduced the need for psychotropic medications to treat BPSD. Dual inhibition of AChE and BuChE and brain-region selectivity through preferential inhibition of the G1 isoform of AChE may provide the underlying reasons for the apparently greater and broader efficacy of rivastigmine over AChE-selective inhibitors for the treatment of BPSD. However, randomised, controlled trials are required to compare dual inhibitors, such as rivastigmine, and AChE-selective agents, to confirm and quantify any differences in their effects on BPSD.

Topics: Behavioral Symptoms; Carbamates; Cholinesterase Inhibitors; Dementia; Donepezil; Galantamine; Humans; Indans; Nootropic Agents; Phenylcarbamates; Piperidines; Rivastigmine; Treatment Outcome

Cholinesterase inhibitors (ChEIs) are dosed in two phases for the treatment of dementia, an initial dose-escalation phase to achieve a therapeutic dose and a maintenance phase where the therapeutic dose is given for long-term therapy. ChEIs are associated with a range of side effects as a result of cholinergic stimulation in different areas of the brain and the periphery Acute, centrally-mediated gastrointestinal events (mostly nausea and vomiting) are class effects of all ChEIs, and are reported mostly during the dose-escalation phase of therapy. These events have been associated more with the dual acetylcholinesterase/butyrylcholinesterase (AChE/BuChE) inhibitor rivastigmine than with the AChE-selective inhibitors donepezil and galantamine, probably due to rivastigmine's higher potency. However, these events can be minimised using slow dose escalation with small dose graduations and administration with food. Other side effects associated with ChEIs include central nervous system events, extrapyramidal symptoms, sleep disturbances and cardiorespiratory events, associated with cholinergic activity in the cortex, caudate nucleus, brainstem and medulla, respectively, and muscle cramps and weakness, cardiorespiratory events and urinary incontinence, associated with peripheral cholinergic activity. These symptoms are mostly reported during the maintenance phase of therapy. They are more frequently reported with donepezil, but are rarely reported with rivastigmine, and galantamine may not have been marketed long enough to make an adequate assessment. These differences are due to the drugs' respective pharmacology. For example, donepezil and rivastigmine are active centrally, in contrast to galantamine, which is more active peripherally. Furthermore, rivastigmine preferentially inhibits the G1 isoform of cholinesterase, predominantly located in the cortex, hippocampus and in neuritic plaques, while donepezil and galantamine are not selective for any cholinesterase isoforms and have wide cholinergic activity both centrally and peripherally The cholinergic activity of rivastigmine, in contrast to donepezil and galantamine, is apparently more targeted at clinically relevant brain sites. The pharmacological profile of rivastigmine results in it having a low potential to interact with other drugs and it may be used with a high margin of safety in patients having a wide variety of concomitant diseases. Donepezil and galantamine may have significant interactions with

Topics: Carbamates; Cholinesterase Inhibitors; Dementia; Donepezil; Galantamine; Humans; Indans; Nootropic Agents; Phenylcarbamates; Piperidines; Rivastigmine

Many neuropsychiatric disorders affect memory. Brain regions important in the neuroanatomic substrate of memory include the hippocampus, and sections of the frontal, temporal, and parietal cortices and the thalamus. Acetylcholine and many other neurotransmitters and neuromodulators including dopamine, glutamate, GABA, the catecholamines, and estrogen modulate cognitive function. Treatment approaches to memory loss typically use Alzheimer's dementia as the template, and are discussed in this report.

Topics: Aging; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cholinesterase Inhibitors; Dementia; Donepezil; Estrogen Replacement Therapy; Humans; Indans; Memory Disorders; Nootropic Agents; Piperidines; Premenopause; Randomized Controlled Trials as Topic; Tacrine

Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of new drugs is essential. The application of this information facilitates the design of a rational clinical trial programme and optimizes the chances for rapid and successful clinical development. Upon completion of each development phase, the information obtained must be evaluated critically to maximize the design of subsequent studies. Phase I trials represent the first time the drug is administered in humans and their primary objective is to evaluate the drug's safety and tolerability in man. Phase II trials represent the first time that the drug is administered to the target patient population. The objectives of Phase II trials are to verify the safety and tolerability of the drug in patients, and also to evaluate for the first time the clinical efficacy of the drug. During these phases of development, the use of PK and PD measures is helpful for establishing the therapeutic dose range as well as the suitability of the chosen efficacy measures for use in the pivotal Phase III trials. Here, using several examples of PK and PD data obtained from the clinical development studies of donepezil HCl, the application of these measures on the development of a drug for the treatment of Alzheimer's disease is discussed.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Clinical Trials as Topic; Dementia; Donepezil; Drug Design; Humans; Indans; Nootropic Agents; Piperidines

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Ginkgo biloba; Humans; Indans; Neuroprotective Agents; Nootropic Agents; Phytotherapy; Piperidines; Plants, Medicinal; Selegiline; Tacrine; Vitamin E

Therapeutic approaches to the cognitive impairment of dementia are making their way into clinical practice. Clinical pharmacologic approaches toward improvement of cognitive symptoms are discussed, with an emphasis on cholinergic approaches, since they currently appear most promising and since several cholinesterase inhibitors may soon be available for prescribing. As more knowledge is gained about dosing, side effects, and mechanisms of action, these drugs can be prescribed more efficiently. Current research approaches to slowing the rate of cognitive decline are discussed, including the use of antioxidants, monoamine oxidase-B inhibitors, and cholinesterase inhibitors. Drugs that improve cognition may also have effects on behavioral symptoms, severe dementia, and non-Alzheimer's dementia. Evidence suggests that some dementia patients may be particularly responsive to intervention and that other medications may enhance response. Psychosocial interventions may also contribute to prolonging the time to institutionalization.

Topics: Aged; Alzheimer Disease; Antioxidants; Carbamates; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Humans; Indans; Monoamine Oxidase Inhibitors; Phenylcarbamates; Piperidines; Rivastigmine; Tacrine; Trichlorfon

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Indans; Male; Piperidines; Tacrine; United States

Topics: Adolescent; Adult; Aged; Alcoholism; Antisocial Personality Disorder; Child; Dementia; Epilepsy; Female; Humans; Intellectual Disability; Male; Mental Disorders; Middle Aged; Neurotic Disorders; Nitriles; Paranoid Disorders; Personality Disorders; Phenothiazines; Piperidines; Psychotic Disorders; Schizophrenia; Tranquilizing Agents

Topics: Cholinesterase Inhibitors; Dementia; Humans; Piperidines

Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HT. We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) at weeks 8 and 12 were randomly assigned in a 1:1 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end point, assessed in a time-to-event analysis, was a relapse of psychosis as defined by any of the following: an increase of at least 30% in the SAPS-H+D score and a CGI-I score of 6 (much worse) or 7 (very much worse), hospitalization for dementia-related psychosis, stopping of the trial regimen or withdrawal from the trial for lack of efficacy, or use of antipsychotic agents for dementia-related psychosis.. Of the 392 patients in the open-label phase, 41 were withdrawn for administrative reasons because the trial was stopped for efficacy; of the remaining 351 patients, 217 (61.8%) had a sustained response, of whom 105 were assigned to receive pimavanserin and 112 to receive placebo. A relapse occurred in 12 of 95 patients (13%) in the pimavanserin group and in 28 of 99 (28%) in the placebo group (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.73; P = 0.005). During the double-blind phase, adverse events occurred in 43 of 105 patients (41.0%) in the pimavanserin group and in 41 of 112 (36.6%) in the placebo group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin.. In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dementia; Double-Blind Method; Female; Hallucinations; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Parkinson Disease; Piperidines; Proportional Hazards Models; Psychotic Disorders; Recurrence; Urea

To evaluate the adequacy of using the consensus diagnostic criteria for dementia with Lewy bodies (DLB) to recruit patients with homogeneous characteristics in future clinical trials, where multiple departments of multinational centres are expected to participate with a long enrolment period, and additionally, to contribute to the possible future criteria revision.. Using data from 2 trials of donepezil for DLB, conducted 3 years apart, characteristics in patients with probable DLB were analysed and compared between studies and between psychiatric and neurological centres.. In 273 patients (phase II: 135, phase III: 138; psychiatric: 73, neurological: 184), clinical characteristics overall were very similar between studies, and between specialty centres, excluding distinctive parkinsonism in the neurological versus psychiatric centres: incidence of parkinsonism (91.8 vs. 71.2%, p < 0.001), Hoehn and Yahr stage (III: 55.0 vs. 21.2%, p < 0.001), and concomitant anti-Parkinson medication (24.5 vs. 11.0%, p = 0.017). Rapid eye movement sleep behaviour disorder, depression, and delusion, suggestive or supportive features, were observed in 35-40%. Additionally, a high prevalence (55.3%) of anxiety was observed.. Employing the consensus criteria is adequate to enrol homogeneous DLB patients into future clinical trials regardless of the specialty of centres and time. Further discussion could involve adding anxiety to future criteria.

Topics: Aged; Aged, 80 and over; Consensus; Dementia; Donepezil; Female; Guideline Adherence; Humans; Indans; Lewy Body Disease; Male; Piperidines; Practice Guidelines as Topic; Psychiatric Status Rating Scales

There is a lack of knowledge about antidementia drug treatment in community dwelling people with dementia in Germany.. To determine the frequency of treatment with antidementia drugs in patients in primary care, and the socio-demographic and clinical variables associated with antidementia drug treatment.. Present analyses are based on preliminary data from the DelpHi-trial, an ongoing GP-based, cluster-randomized, controlled intervention trial to implement and evaluate an innovative concept of collaborative dementia care management in Germany. Our sample consists of n = 243 subjects who screened positive for dementia.. 29.6% (n = 72) of participants received antidementia drugs: memantine 44.5% (n = 32); donepezil 30.5% (n = 22); rivastigmine 13.9% (n = 10); galantamine 11.1% (n = 8). A total of 46.4% (n = 45) of the subgroup of participants with a formal dementia diagnosis received antidementia drug treatment. Approximately 37.5% (n = 27) of our sample received treatment with antidementia drugs without having a formal diagnosis. Treatment with antidementia drugs was significantly associated with more severe cognitive impairment and having a formal dementia diagnosis.. One in three people who screened positive for dementia in primary care received antidementia drug treatment, indicating the frequent use of this class of drugs. For those with a formal dementia diagnosis, these drug treatment rates are more than triple, compared to those in nursing homes.

Topics: Aged; Aged, 80 and over; Dementia; Donepezil; Female; Galantamine; Humans; Indans; Male; Memantine; Mental Status Schedule; Neuropsychological Tests; Nootropic Agents; Phenylcarbamates; Piperidines; Primary Health Care; Rivastigmine

To observe the intervention effect of nourishing Xin and Shen method (NXSM) on the cognitive function of mild cognitive impairment due to subcortical small vessel disease (MCI-SSVD).. All 54 MCI-SSVD patients came from Department of Traditional Chinese Medicine, Affiliated Union Hospital of Fujian Medical University from June 2010 to August 2013. They were randomly assigned to the treatment group (28 cases) and the control group (26 cases). Another 33 volunteers were recruited as a healthy control group. On the basis of targeting risk factors of blood vessels, MCI-SSVD patients were treated respectively with NXSM and donepezil hydrochloride, with the therapeutic course of 12 weeks. Neuropsychological scales [mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA)], and Chinese medical dementia syndrome scales were performed in all subjects, and results were compared among groups or intra-group before and after treatment.. MMSE and MoCA scores of the two treatment groups decreased more, when compared with those of the healthy control group (P < 0.05). In particular, MoCA score was significantly decreased (P < 0.01). MMSE and MoCA scores of the two treatment groups increased more after treatment than before treatment (P < 0.05). But there was no statistical difference in MMSE or MOCA score after treatment between the two groups (P > 0.05). Chinese medical dementia syndrome scales decreased more significantly in the treatment group, when compared with before treatment (P < 0.01). But there was no statistical difference in Chinese medical dementia syndrome scales in the control group between before and after treatment (P > 0.05). Visual spatial and executive function scores or delayed recall scores of the two treatment groups increased more, when compared with the same group before treatment (P < 0.05, P < 0.01).. NXSM could effectively improve cognitive functions of MCI-SSVD.

Topics: Alzheimer Disease; Biomedical Research; Cognition; Cognitive Dysfunction; Dementia; Donepezil; Drugs, Chinese Herbal; Humans; Indans; Neuropsychological Tests; Piperidines

Here we conducted a randomized and double-blind study attempting to explore the safety and efficacy of combined therapy of Di-Huang-Yi-Zhi (DHYZ) with donepezil in treating Parkinson's disease dementia (PDD). Sixty PDD patients were included and randomly divided into control group and DHYZ group. All patients were given donepezil (5 mg last for a month, then 10 mg for the rest months, once daily), while patients in DHYZ group were additionally administrated with DHYZ (150 ml, twice daily). The measurement subjects included mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Barthel Index for activities of daily living (ADL) and Traditional Chinese medical (TCM) symptoms before and after treatment in this study. The whole study lasted for six months. Significant differences were observed on MMSE, MoCA, ADAS-Cog, ADL and TCM in both control and DHYZ group (P<0.05 or P<0.01) before and after drug treatment. Furthermore, there were more obvious changes of MMSE, MoCA, ADAS-Cog, ADL and TCM scores compared the DHYZ group with the control group (P<0.01) which suggested the DHYZ group showed a more effective improvement on cognition, behavior as well global function. In conclusion, the combined therapy of DHYZ with donepezil showed a more effective improvement in PDD and the underlying mechanism may be related to the synergic amelioration of cholinergic system between them.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Dementia; Donepezil; Double-Blind Method; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Indans; Male; Middle Aged; Parkinson Disease; Piperidines

Behavioral and psychological symptoms of dementia (BPSD) occur in up to 80% of Alzheimer's disease (AD) patients and represent one of the most common reasons for early institutionalization and increase in management costs.. This study evaluated the effects of four drugs (memantine, donepezil, rivastigmine, galantamine) in BPSD in AD patients.. This was a prospective, longitudinal, randomized, open-label, 4-arm, parallel-group, 12-month clinical trial carried out in 177 AD patients. The severity of BPSD was evaluated at baseline and after treatment with memantine (n = 48), donepezil (n = 42), rivastigmine (n = 46), and galantamine (n = 41), by using the Neuropsychiatric Inventory (NPI) and the Behavioural Pathology in Alzheimer's Disease (BEHAVE-AD) scales.. The NPI and BEHAVE-AD total scores improved from baseline to month 12 in all groups. The improvements in both scales were statistically significant in the memantine, donepezil, and rivastigmine groups, but not in the galantamine group. Responder analyses showed that treatment with memantine and rivastigmine resulted in more patients improving on NPI and BEHAVE-AD score, respectively. Agitation/aggression was the NPI item with the highest improvements (significantly versus baseline in the memantine and in the rivastigmine groups), while aggression and anxiety/phobias were the mostly improved BEHAVE-AD items (significantly in the rivastigmine group for both and in the rivastigmine group only for anxiety/phobias). All treatments were well tolerated: most of adverse events reported were transient and of mild-to-moderate intensity.. This study suggests that specific drugs for AD, especially memantine and rivastigmine, may be effective in the improvement of BPSD in patients with mild to moderate AD, without major side effects.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Behavioral Symptoms; Cholinesterase Inhibitors; Dementia; Donepezil; Excitatory Amino Acid Antagonists; Female; Galantamine; Humans; Indans; Longitudinal Studies; Male; Memantine; Mental Disorders; Phenylcarbamates; Piperidines; Psychiatric Status Rating Scales; Rivastigmine

vascular dementia (VaD) and mixed Alzheimer's disease (AD/VaD) are common. How best to monitor treatment is not clear. Our objective was to compare responsiveness and construct validity of change scores, following donepezil treatment, of the standardized Mini-Mental State Examination (sMMSE) and other measures potentially usable in primary care.. A six-month, outcome measurement study. The Disability Assessment for Dementia (DAD), CLOX-1 and 2, Phonetic Fluency, a short Neuropsychiatric Inventory, (the NPI-Q), Clinical Global Impression (CGI) and the SymptomGuide™ (SG) were measured. Construct validity was tested by correlating change scores, and responsiveness by calculating standardized response means (SRMs).. Of 148 treated patients, 116 completed. The mean sMMSE increased by 0.7 (95% Confidence Interval (CI) = -0.005, 1.41; p=0.06; SRM= 0.15). There was no statistically significant difference in the DAD. The NPI-Q (-1.4; 95% CI = -2.08, -0.72; p<0.01; SRM=0.24), CLOX-1 (0.9; 95% CI = 0.19, 1.61; p<0.01; SRM=0.21), CLOX-2 (0.9; 95% CI = 0.17, 1.63; p=0.03; SRM=0.26), Phonetic Fluency (0.9; 95% CI = 0.19, 1.61; p=0.02; SRM=0.21) and SG (0.35; 95% CI = 0.20,0.51; p<0.01; SRM=0.28) each detected significant improvement. The CGI suggested improvement in 74 completers (64%) - mostly "minimal" (44/116, 38%) - while 21/116 (18%) were worse. Change scores at 24 weeks were at best modestly correlated with each other (range -0.22 to 0.30).. Different measures showed different responsiveness, in a setting in which the mean treatment effect seems to have been small, but clinically detectable. Patient-centered and executive function measures might be useful in vascular and mixed dementia.

Topics: Aged; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Female; Humans; Indans; Male; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Treatment Outcome

Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+; global function). Secondary end points measured executive function, attention, activities of daily living (ADLs), and behavioral symptoms. Safety and tolerability were assessed. ADAS-cog mean changes from baseline to week 24 (end point) were not significant for donepezil in the intent-to-treat population by the predefined statistical model (difference from placebo: -1.45, P = .050, for 5 mg; -1.45, P = .076, for 10 mg). Alternative ADAS-cog analysis, removing the treatment-by-country interaction term from the model, revealed significant, dose-dependent benefit with donepezil (difference from placebo: -2.08, P = .002, for 5 mg; -3.31, P < .001, for 10 mg). The 10-mg group, but not the 5-mg group, had significantly better CIBIC+ scores compared with placebo (3.7 vs 3.9, P = .113, for 5 mg; 3.6 vs 3.9, P = .040, for 10 mg). Secondary end points-Mini-Mental State Exam; Delis-Kaplan Executive Function System; Brief Test of Attention, representing cognitive functions particularly relevant to PDD-showed significant benefit for both donepezil doses (P ≤ .007). There were no significant differences in ADLs or behavior. Adverse events were more common with donepezil but mostly mild/moderate in severity. Although the study did not achieve its predefined primary end points, it presents evidence suggesting that donepezil can improve cognition, executive function, and global status in PDD. Tolerability was consistent with the known safety profile of donepezil. © 2012 Movement Disorder Society.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Cholinesterase Inhibitors; Dementia; Donepezil; Dose-Response Relationship, Drug; Double-Blind Method; Europe; Female; Humans; Indans; Male; Middle Aged; Parkinson Disease; Piperidines; Psychiatric Status Rating Scales

White matter hyperintensities (WMH) have an effect on cognition and are increased in severity among individuals with amnestic mild cognitive impairment (aMCI). The influence of WMH on progression of aMCI to Alzheimer's disease (AD) is less clear.. Data were drawn from a three-year prospective, double blind, placebo controlled clinical trial that examined the effect of donepezil or vitamin E on progression from aMCI to AD. WMH from multiple brain regions were scored on MR images obtained at entry into the trial from a subset of 152 study participants using a standardized visual rating scale. Cox proportional hazards models adjusting for age, education and treatment arm were used to investigate the role of WMH on time to progression.. 55 of the 152 (36.2 %) aMCI subjects progressed to AD. Only periventricular hyperintensities (PVH) were related to an increased risk of AD within three years (HR = 1.59, 95 % CI = 1.24 - 2.05, p-value < 0.001). Correcting for medial temporal lobe atrophy or the presence of lacunes did not change statistical significance.. PVH are associated with an increased risk of progression from aMCI to AD. This suggests that PVH, an MRI finding thought to represent cerebrovascular damage, contributes to AD onset in vulnerable individuals independent of Alzheimer pathology.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amnesia; Antioxidants; Atrophy; Brain; Cerebral Ventricles; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Disease Progression; Donepezil; Double-Blind Method; Female; Humans; Image Processing, Computer-Assisted; Indans; Magnetic Resonance Imaging; Male; Piperidines; Prospective Studies; Temporal Lobe; Time Factors; Treatment Outcome; Vitamin E

We examined attention-enhancing effects of the cholinesterase inhibitor donepezil in Dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) by means of open label study.. 22 DLBs and 23 PDDs were assessed over 20 weeks using the Cognitive Drug Research Computerized Attentional Tasks. We examined how much closer our patients moved towards being normal for their age by comparing them to a non-demented elderly control sample (n = 183, aged 71-75 years).. Donepezil treatment improved power of attention, continuity of attention and reaction time variability. The deficit in responses was moved towards normal by 38 and 56% for power of attention and 22 and 10% for continuity of attention in PDD and DLB, respectively.. Improvements in attention were found with donepezil in PDD and DLB.

Topics: Aged; Aged, 80 and over; Attention; Chi-Square Distribution; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Female; Humans; Indans; Lewy Body Disease; Male; Mental Processes; Middle Aged; Nootropic Agents; Parkinson Disease; Piperidines; Reaction Time; Reference Values; Statistics, Nonparametric; Treatment Outcome

The objective of this study was to evaluate donepezil, an acetylcholinesterase inhibitor, in the treatment of frontotemporal dementia (FTD).. Twelve patients with FTD who received donepezil for six months were compared with 12 FTD controls on behavioral measures.. The groups did not differ on most variables at baseline or at six months; however, the donepezil group had greater worsening on the FTD Inventory. Four treated patients had increased disinhibited or compulsive acts, which abated with discontinuation of the medication.. There were no changes in global cognitive performance or dementia severity; however, a subgroup of patients with FTD can experience worsening of symptoms with donepezil.

Topics: Behavioral Symptoms; Cholinesterase Inhibitors; Compulsive Behavior; Dementia; Donepezil; Female; Humans; Indans; Male; Middle Aged; Piperidines

Individuals diagnosed as having mild cognitive impairment (MCI) have a high likelihood of progressing to dementia within 3 to 5 years, but not all individuals with MCI progress to dementia. Prognostic uncertainty suggests the need for additional measures to assist the clinician.. To assess the added value of qualitative measures of medial temporal atrophy (MTA) to estimate the relative risk of progressing from MCI to dementia.. A 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study initially designed to evaluate the efficacy of donepezil hydrochloride or vitamin E vs placebo to delay progression of MCI to dementia.. Memory assessment centers.. A total of 190 individuals with MCI.. Ratings of MTA performed using magnetic resonance images obtained at baseline. Log-rank tests and Cox proportional hazards ratios examining the significance of MTA estimates in predicting progression of MCI to dementia.. A mean MTA score greater than 2.0 was associated with a greater than 2-fold increased likelihood of progression to dementia during the observation period (hazards ratio, 2.30; 95% confidence interval, 1.09-4.92; P = .03) after controlling for age, education, sex, and baseline Mini-Mental State Examination score.. Adjusted estimates of MTA were associated with significantly increased risk of developing dementia within 3 years, suggesting that obtaining a magnetic resonance image during the evaluation of MCI may offer additional independent information about the risk of progression to dementia. Given the relatively high prevalence of MCI in the general population, use of this method as part of routine clinical evaluation may help identify individuals who might benefit from increased surveillance and future treatment.. clinicaltrials.gov Identifier: NCT00000173.

Topics: Aged; Aged, 80 and over; Atrophy; Cognition Disorders; Dementia; Disease Progression; Donepezil; Double-Blind Method; Female; Humans; Indans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Nootropic Agents; Piperidines; Predictive Value of Tests; Reproducibility of Results; Temporal Lobe; Vitamin E

To assess the efficacy and tolerability of quetiapine for agitation or psychosis in patients with dementia and parkinsonism.. Multicenter randomized, double-blind, placebo-controlled parallel groups clinical trial involving 40 patients with dementia with Lewy bodies (n = 23), Parkinson disease (PD) with dementia (n = 9), or Alzheimer disease with parkinsonian features (n = 8). The main outcome measure for efficacy was change in the Brief Psychiatric Rating Scale (BPRS) from baseline to 10 weeks of therapy. For tolerability it was change in the Unified PD Rating Scale (UPDRS) motor section over the same time period. The trial was confounded by the need for a design change and incomplete recruitment.. No significant differences in the primary or secondary outcome measures of efficacy were observed. An unexpectedly large placebo effect, inadequate dosage (mean 120 mg/day), and inadequate power may have contributed to lack of demonstrable benefit. Quetiapine was generally well-tolerated and did not worsen parkinsonism, but was associated with a trend toward a decline on a measure of daily functioning.. Quetiapine was well-tolerated and did not worsen parkinsonism. Although conclusions about efficacy may be limited, the drug in the dosages used did not show demonstrable benefit for treating agitation or psychosis in patients with dementia and parkinsonism. These findings are in keeping with prior studies reporting limited efficacy of various medications for reducing behavioral problems in demented patients.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antiparkinson Agents; Antipsychotic Agents; Cholinesterase Inhibitors; Confounding Factors, Epidemiologic; Dementia; Dibenzothiazepines; Donepezil; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indans; Lewy Body Disease; Male; Neuropsychological Tests; Parkinson Disease; Patient Selection; Piperidines; Placebo Effect; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Research Design; Severity of Illness Index; Treatment Failure

Cognitive impairment and negative signs are common in patients with schizophrenia. Up to 35% of elderly patients with schizophrenia fulfill the diagnostic criteria of dementia. Donepezil inhibits cholinesterase, thus enhancing cholinergic neurotransmission. We tested the efficacy of donepezil in elderly patients with chronic schizophrenia and severe cognitive impairment.. Following baseline assessment, patients were randomly assigned to receive either donepezil or placebo. The dose was 5 mg daily for the first week and 10 mg for an additional 11 weeks. The procedure was repeated using the crossover compound. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI) and Alzheimer Disease Assessment Scale - Cognitive subscale (ADAS-Cog) were used to assess the severity of symptoms, cognitive status and intervention effects.. Twenty subjects were enrolled (15 females, five males), mean age 70.2 years (SD 6.5) and mean duration of disease 38.5 years (SD 9.3). A modest treatment effect was found for both placebo and donepezil treatment periods. No crossover effect was found. No statistical differences were demonstrated between the two treatment groups (CGI p = 0.37, PANSS p = 0.71, ADAS-Cog p = 0.86). Two patients died during the study period due to unrelated causes and one patient discontinued participation due to increased agitation.. Donepezil does not seem to improve negative signs and cognitive impairment in elderly patients with chronic schizophrenia.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Chronic Disease; Cognition Disorders; Comorbidity; Cross-Over Studies; Dementia; Depressive Disorder; Donepezil; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indans; Male; Middle Aged; Neuropsychological Tests; Nootropic Agents; Piperidines; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Several evidences suggest that cholinergic deficits may significantly contribute to dementia in Parkinson's disease (PDD) and acetylcholinesterase inhibitors (ChEIs) have been reported to improve cognitive symptoms in PDD, without worsening parkinsonism. Nineteen PDD patients underwent brain perfusion SPECT with (99m)Tc-ethyl cysteinate dimer after 6 months ChEIs treatment in order to evaluate the functional correlates of clinical improvement. A clear-cut cognitive improvement was reported in PDD patients with a significant improvement of ADAS-cog total score as well as of subscores exploring executive functions (p<0.01). MMSE total score did not significantly change after ChEIs but the subscore of attention significantly improved after therapy (p<0.01). No difference in motor performance as evaluated by UPDRS was reported. SPM analysis showed a significant increase of perfusion (p < 0.0001) in bilateral cingulate, and frontal regions after ChEIs. Our data confirm the efficacy of ChEIs in the treatment of dementia associated with PD mainly on attention and executive functions, and the functional findings indicate that this cognitive improvement could be associated with a sort of pharmacological frontal "re-afferentation".

Topics: Aged; Antiparkinson Agents; Brain; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Image Processing, Computer-Assisted; Indans; Male; Neuropsychological Tests; Parkinson Disease; Phenylcarbamates; Piperidines; Rivastigmine; Tomography, Emission-Computed, Single-Photon

The objective of this study was to conduct exploratory analyses of data pertaining to the efficacy of donepezil treatment of patients with severe behavioral disturbances. Preliminary studies suggest that cholinesterase inhibitors, including donepezil, may reduce behavioral disturbances in patients with Alzheimer disease (AD). Most patients included in clinical trials have had low levels of psychopathology at baseline, and the effect of cholinesterase inhibitors on patients with more severe behavioral disturbances is unknown. The authors report the effects of donepezil on behavioral disturbances in patients with relatively severe psychopathology at baseline.. This is a hypothesis-driven secondary analysis of a three-phase study involving donepezil and sertraline. In phase 1, psychotropic agents were withdrawn; in phase 2, patients were treated in an open-label fashion with donepezil for 8 weeks; and in phase 3, patients on donepezil were randomized to receive placebo or sertraline for an additional 12 weeks. The data set analyzed is comprised of the patient population treated with donepezil (without sertraline) for 20 weeks. One hundred twenty patients were included in the analyses. Mean age was 76 years, average Mini-Mental State Examination Score was 18, and mean Neuropsychiatric Inventory (NPI) total score was 30. Primary efficacy assessments were the NPI, the Clinical Global Impression-Improvement, and the Clinical Global Impression-Severity scales. Secondary measures included the Behavioral Pathology in Alzheimer's Disease Rating Scale, The Hamilton Depression Rating Scale, and the Alzheimer's Disease Functional Assessment and Change Scale.. Excellent concurrent validity was noted between the NPI and the Behavioral Pathology in Alzheimer's Disease Rating Scale. The total score of the NPI was significantly reduced over the 20 weeks of therapy with donepezil. Sixty-two percent of patients had at least a 30% reduction in the total NPI score (significantly greater than the number with no meaningful response). Likewise, more patients had total or partial resolution of depression and delusions than those who had no meaningful change. Factor analysis of baseline NPI data revealed five factors, including a psychosis factor, an agitation factor, mood factor, frontal lobe function factor, and appetite and eating disorders factor. Clinically meaningful treatment effect sizes were notable for the delusion factor (0.340) and the mood factor (0.39). There were significant correlations between the Clinical Global Impression-Improvement and reductions in mood and agitation scores.. The results of these analyses suggest that donepezil reduces behavioral symptoms, particularly mood disturbances and delusions, in patients with AD with relatively severe psychopathology.

Topics: Aged; Cholinesterase Inhibitors; Dementia; Demography; Donepezil; Double-Blind Method; Factor Analysis, Statistical; Female; Humans; Indans; Male; Mental Disorders; Middle Aged; Piperidines; Prevalence; Sertraline; Severity of Illness Index; Treatment Outcome

The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50-80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients' conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Cholinesterase Inhibitors; Dementia; Donepezil; Double-Blind Method; Female; Ginkgo biloba; Humans; Indans; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Piperidines; Plant Extracts

Inhibition of acetylcholinesterase improves symptoms of dementia in patients with Parkinson's disease (PD). Dementia in PD has a cumulative incidence of up to 80% and is mainly caused by a distinct cholinergic deficit. Objectives of this investigator initiated multicenter open label trial were to confirm the efficacy of donepezil in the treatment of dementia in PD patients and to investigate the tolerability and safety of donepezil. The Mini Mental State Examination (MMSE)-score significantly increased in patients, who finished the trial. A detailed analysis of the various items of the MMSE revealed, that only task performance of orientation and recall significantly improved. Scores of the short syndrome test and the Clinical Global Impression Scale improved, motor impairment did not increase. Only 14 out of 24 PD patients finished the trial due to predominant onset of vomiting, nausea, dizziness and confusion. This may result from the titration regime of donepezil, that allows only 5 and 10 mg dosages. Participants with premature study termination had a significant longer duration of PD, less motivation and sleep disturbances at night. Treatment with donepezil was only effective in PD patients with dementia, who experience nearly no side effects from the drug.

Topics: Aged; Analysis of Variance; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Indans; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Parkinson Disease; Piperidines; Time Factors

To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD).. This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5-10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog).. Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale.There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant.. Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study.

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Cross-Over Studies; Dementia; Donepezil; Double-Blind Method; Female; Humans; Indans; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Piperidines; Treatment Outcome

Impairments of memory are often found after rupture and repair of aneurysms leading to a basal forebrain lesion. This open study investigated whether cholinergic substitution therapy may be a treatment option. The effect of donepezil, a cholinesterase inhibitor on memory functions was tested in an open-label, exploratory study in 11 patients with a chronic amnestic syndrome from a ruptured and repaired aneurysm of the anterior communicating artery (seven patients), the anterior cerebral (two) or the pericallosal artery (two). Mean time since onset was 75.4 months. Memory was evaluated at baseline and consecutively after 4 weeks of 5 mg donepezil daily, 8 weeks of 10 mg donepezil, and 4 weeks after drug discontinuation. Memory functions were assessed using the California Verbal Learning Test and compared with a matched group of normal, untreated controls. Tests of attention and of executive functions were also administered. Donepezil was well tolerated. Strong group effects were found at baseline and at all follow-up measurements showing profound impairments of memory functions in the patient group. Within patient statistics showed significant improvements of short and long delay free recall scores during the treatment period, both with 5 and 10 mg donepezil daily, whereas attentional and executive functions improved only non-significantly. Memory functions decreased after drug discontinuation. Repeated test administration in the control group also showed an increase of memory scores which was minor when compared with the performance change in the patient group. Donepezil may improve episodic memory functions in patients suffering from a chronic amnestic syndrome caused by rupture and repair of aneurysms of the anterior communicating, the anterior cerebral or the pericallosal artery. Future doubled-blind, placebo-controlled trials are warranted to confirm these findings.

Topics: Adult; Amnesia; Aneurysm, Ruptured; Case-Control Studies; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Administration Schedule; Female; Humans; Indans; Male; Memory; Middle Aged; Neuropsychological Tests; Pilot Projects; Piperidines; Prosencephalon; Statistics, Nonparametric; Time Factors; Treatment Outcome

To evaluate the efficacy and safety of donepezil, an acetylcholinesterase inhibitor, as a treatment for cognitive impairment and dementia in patients with Parkinson' s disease (PD).. Using a randomized, double-blind, placebo-controlled design, nine patients received placebo and seven patients received donepezil (2.5-10 mg/day) for a mean (SD) duration of 15.2 (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory, attention, psychomotor speed, and visuospatial and executive functions. Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings. Primary safety measures were motor signs and assessments of adverse effects.. Patients on donepezil showed selective and significant (p<0.05) improvement on the memory subscale of the Dementia Rating Scale. There was also a trend toward improvement on a measure of psychomotor speed and attention. There were no group differences in psychiatric status, motor function, or activities of daily living as measured at baseline or end-point. Adverse effects resulted in premature withdrawal of four patients on donepezil, two for peripheral cholinergic effects and one for increased parkinsonism. Side effects were associated with dosage increases.. Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment. However, variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD, especially with dosage increases.

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Dementia; Donepezil; Double-Blind Method; Female; Humans; Indans; Male; Memory Disorders; Middle Aged; Neuropsychological Tests; Nootropic Agents; Parkinson Disease; Pilot Projects; Piperidines; Treatment Outcome

A study was performed on patients with Alzheimer's disease (AD) in order to evaluate the efficacy of a combined treatment (donepezil plus cognitive training) in both cognitive processes and affective states. Eighty-six subjects, 25 men and 61 women, with an average age of 75.58 years, were studied. Almost all the subjects had a basic educational level. Donezepil was administered at a dose of 10 mg daily along with cognitive treatment involving images of everyday life and reminiscent music; the sessions took place on Monday to Friday and lasted three quarters of an hour. The study lasted 12 months. Subjects underwent test-retest with the following tests: Mini-Mental State Examination (MMSE), the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog); the Geriatric Depression Scale (GDS) and the overall deterioration scale (FAST). The results showed that subjects receiving the combined treatment had a better response than those who did not receive any cognitive training. These subjects' MMSE score decreased by 3.24 on average. The affective symptomatology of those receiving only drug treatment improved whereas the cognitive processes did not.

Topics: Aged; Aging; Alzheimer Disease; Cholinergic Agents; Cognition; Cognitive Behavioral Therapy; Combined Modality Therapy; Dementia; Donepezil; Female; Humans; Indans; Long-Term Care; Male; Neuropsychological Tests; Nootropic Agents; Piperidines; Sex Characteristics

Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer's disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms2; p = 0.001) but also for total power (median changed from 1,563 to 844 ms2; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.

Topics: Aged; Autonomic Nervous System; Cardiovascular System; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Heart Rate; Humans; Indans; Male; Pilot Projects; Piperidines; Regression Analysis; Sampling Studies; Syncope

Centrally acting cholinesterase inhibitors (ChEIs) improve cognitive functions in Alzheimer's disease (AD) and other forms of dementia. Evaluation of treatment efficacy is based mainly on subjective assessment methods such as standardized neuropsychological tests. Therefore, an additional objective tool for the evaluation of drug response would be most helpful.Thirty-two patients suffering from dementia of several etiologies were treated with ChEIs (tacrine 19, donepezil 5, rivastigmine 8). Cognitive response was assessed pre ChEIs initiation (baseline) and after 26 weeks, as optimal tolerated doses were achieved and maintained (endpoint). Evaluation included repeated measurements of Mini Mental State Examination (MMSE), Alzheimer's disease assessment scale cognitive part (ADAS-cog) and P300. For statistical analysis we used ANOVA with repeated measures and Pearson correlation coefficient. Results demonstrated improvement of mean ADAS-cog by 2.0 points (from 29.4, n = 31 to 27.4, n = 29; p = 0.08) while MMSE remained almost unchanged (20.1, n = 29 to 19.8, n = 28). Mean P300 latency reduced significantly by 24 ms (from 383 +/- 7.9 msec, n = 32 to 359 +/- 7 msec, n = 32; p = 0.0001). However mean amplitudes did not change significantly from baseline to endpoint (13.5 +/- 6.2, n = 31 to 12.8 +/- 6.1, n = 31). Significant correlations were found between mean ADAS-cog and mean P300 latency at baseline and end-point (R = 0.485 p = 0.019, R = 0.626 p = 0.001 respectively, n = 23) and between mean MMSE and P300 latency at baseline and endpoint (R = -0.420 p = 0.046, R = -0.703 p < 0.001 respectively, n = 23). Our data suggests that P300 is a reliable instrument for assessment of cognitive response to ChEIs in demented patients.

Topics: Acetylcholine; Aged; Carbamates; Cerebral Cortex; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Electroencephalography; Event-Related Potentials, P300; Female; Humans; Indans; Male; Middle Aged; Phenylcarbamates; Piperidines; Prospective Studies; Reaction Time; Rivastigmine; Tacrine; Treatment Outcome

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Down Syndrome; Humans; Indans; Long-Term Care; Middle Aged; Neuropsychological Tests; Piperidines

This open label study was designed to assess the effects of donepezil treatment, its withdrawal and subsequent recommencement on cognitive functioning, behaviour and parkinsonian symptoms in patients with probable dementia with Lewy bodies (DLB) and with Parkinson's disease who subsequently developed dementia (PDD).. Eight patients with DLB and 11 with PDD were treated with up to 10 mg of donepezil daily for 20 weeks followed by a 6-week withdrawal period. The primary outcome measures were the Mini-Mental State Examination (MMSE), the total Neuropsychiatric Inventory (NPI) and the Unified Parkinson's Disease Rating Scale III. Testing was conducted before dosing, at week 20, at a withdrawal visit and 3 months after recommencement on donepezil.. Patients with DLB and PDD showed a significant improvement in cognition with treatment, loss of this improvement on withdrawal and restoration of treatment gains on recommencement. Both groups also demonstrated favourable, behavioural changes with treatment, PDD patients in particular deteriorating significantly after withdrawal. The only NPI symptom domain that showed a consistent significant response to both treatment (positive) and withdrawal (negative) was hallucinations. The medication was well tolerated and parkinsonian features did not alter significantly over the testing sessions.. Our results suggest that treatment with donepezil improves cognition and hallucinations without increasing parkinsonian symptoms, and its sudden withdrawal is usually detrimental, producing acute cognitive and behavioural decline. Although recommencement on donepezil appears to reverse this deterioration we do not advise its abrupt discontinuation in this population.

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Drug Administration Schedule; Humans; Indans; Lewy Body Disease; Neuropsychological Tests; Nootropic Agents; Parkinson Disease; Piperidines; Psychiatric Status Rating Scales; Treatment Outcome

Until recently, conventional antipsychotics were the standard pharmacotherapy for psychosis and behavioral disturbances associated with dementia. This double-blind, placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia.. Eighty-five hospitalized patients with at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions) were randomly assigned to receive either citalopram, perphenazine, or placebo under double-blind conditions for up to 17 days.. Patients treated with citalopram or perphenazine showed statistically significant improvement on several Neurobehavioral Rating Scale factor scores. Compared to those receiving placebo, only patients treated with citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors. Side effect scores were similar among the three treatment groups.. Citalopram was found to be more efficacious than placebo in the short-term hospital treatment of psychotic symptoms and behavioral disturbances in nondepressed, demented patients.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Behavioral Symptoms; Citalopram; Dementia; Donepezil; Double-Blind Method; Drug Therapy, Combination; Female; Hospitalization; Humans; Indans; Male; Perphenazine; Piperidines; Placebos; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Adaptation, Psychological; Adult; Cholinesterase Inhibitors; Dementia; Donepezil; Down Syndrome; Drug Administration Schedule; Female; Humans; Indans; Intelligence Tests; Male; Middle Aged; Piperidines; Treatment Outcome

Dementia with Lewy bodies (DLB) is common. Symptomatic treatment can be difficult. We reviewed nine consecutive patients with DLB (mean age 77.5 [range 67 to 84] years; seven men and two women; mean duration of disease 3.7 [range 1.5 to 8.0] years) who had been treated with donepezil. Each initially received 2.5 to 5 mg per day of donepezil, and was stabilized on 5 mg per day. Donepezil was increased to 10 mg per day in five patients. The mean observation period was 12 (range 8 to 24) weeks. Target symptoms included cognition, hallucinations, parkinsonism, and functional abilities. By both cognitive testing and family reports, cognition improved in seven of nine patients, remained the same in one of nine, and fluctuated in one of nine (mean Mini-Mental State Examination change 4.4 +/- 6.3 points). Function was improved or maintained in six of nine patients and fluctuated in two of nine. Hallucinations initially worsened, then fluctuated in one patient, but improvement in frequency, duration, and content was reported in eight of nine cases. In three of nine patients, treatment with donepezil resulted in worsening of parkinsonism, which in each case responded to levodopa/carbidopa. Treatment of DLB patients with donepezil for 12 weeks most commonly improved hallucinations, and sometimes improved cognition and overall function. Treatment with donepezil was sometimes associated with worse parkinsonism.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Dementia; Donepezil; Female; Geriatric Assessment; Humans; Indans; Lewy Bodies; Male; Mental Status Schedule; Nootropic Agents; Parkinson Disease, Secondary; Piperidines

Topics: Aged; Analysis of Variance; Dementia; Female; Humans; Male; Mental Disorders; Minerals; Piperidines; Placebos; Psychological Tests; Vitamins

Topics: Aged; Butyrophenones; Clinical Trials as Topic; Dementia; Female; Humans; Male; Piperidines; Promazine; Tranquilizing Agents

Topics: Aged; Butyrophenones; Clinical Trials as Topic; Dementia; Female; Humans; Male; Middle Aged; Piperidines; Promazine; Tranquilizing Agents

Topics: Dementia; Humans; Piperidines; Psychotic Disorders; Urea

Dysfunction of the cholinergic basal forebrain (BF) neurotransmitter system, including cholinergic axon denervation of the cortex, plays an important role in cognitive decline and dementia. A validated method to directly quantify cortical cholinergic terminal integrity enables exploration of the involvement of this system in diverse cognitive profiles associated with dementia, particularly at a prodromal stage. In this study, we used the radiotracer [

Topics: Alzheimer Disease; Amyloid beta-Peptides; Basal Forebrain; Cholinergic Agents; Cognitive Dysfunction; Dementia; Humans; Magnetic Resonance Imaging; Piperidines; Positron-Emission Tomography

Topics: Antipsychotic Agents; Dementia; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Urea

A pair of stereoisomers of new 4,5-dihydroxypiperine was isolated from P. retrofractum and showed profound activity on AlCl

Topics: Alkaloids; Aluminum Chloride; Animals; Behavior Therapy; Benzodioxoles; Dementia; Dose-Response Relationship, Drug; Molecular Structure; Piperaceae; Piperidines; Polyunsaturated Alkamides; Structure-Activity Relationship; Zebrafish

Topics: Dementia; Humans; Piperidines; Psychotic Disorders; Urea

Topics: Clinical Trials as Topic; Dementia; Humans; Piperidines; Psychotic Disorders; Urea

This article is to investigate the effect of piperine on the small intestine of mice with Parkinson's disease with dementia(PDD). Ninety-six C57 BL/6 mice of SPF grade were randomly divided into 8 groups(male, 12 in each group): normal group, model group, autophagy inhibitor group(6-amino-3-methylpurine, 3 MA, 30 mg·kg~(-1)), autophagy activator group(rapamycin, 1 mg·kg~(-1)), low, medium, and high dose piperine groups(10, 20, 40 mg·kg~(-1)), and medopar group(112.5 mg·kg~(-1)). Except for the normal group, mice in each group were injected subcutaneously with reserpine(0.1 mg·kg~(-1)) once every 48 hours for 40 days. In addition, on the 20 th day of administration, except for the normal group, the mice in the other groups were subjected to bilateral common carotid artery occlusion to finally prepare PDD models. At the same time, each group was given the corresponding drug treatment once a day for 40 days. After the last administration, the behavioral changes of mice were observed by autonomic activity experiment and hot plate experiment. The expression levels of α-synuclein(α-syn) and tyrosine hydroxylase(TH) in the small intestine were detected by immunohistochemistry. The expression levels of beclin-1, microtubule-associated protein 1 light chain 3 B(LC3 B) and p62 in the small intestine were detected by immunofluorescence assay. Hematoxylin-eosin staining was used to observe the pathological morphology of small intestine tissues in each group. Enzyme-linked immunosorbent assay was adopted for detection of β-amyloid precursor protein(APP), p-tau, acetylcholine transferase(ChAT), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in small intestine. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of α-syn, TH, beclin-1, microtubule-associated protein 1 light chain 3(LC3), and p62 mRNA and mmu-miR-99 a-5 p in the small intestine. The results of this study showed that, as compared with the model group, the number of activities, the expression levels of ChAT, TH, and p62 were significantly increased in the 3 MA group, the various piperine dose groups, and the medopar group(P<0.05), and their first foot licking time was shortened; APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly reduced(P<0.05). However, as compared with the model group, the number of activities, ChAT, TH, and p62 expression levels in the rapamycin group were significantly reduce

Topics: Alkaloids; Animals; Autophagy; Benzodioxoles; Dementia; Intestine, Small; Male; Mice; Parkinson Disease; Piperidines; Polyunsaturated Alkamides

REM sleep behaviour disorder (RBD) occurs frequently in patients with synucleinopathies such as Parkinson's disease, dementia with Lewy body, or multiple system atrophy, but may also occur as a prodromal stage of those diseases; and is termed idiopathic RBD (iRBD) when not accompanied by other symptoms. Cholinergic degeneration of the mesopontine nuclei have been described in synucleinopathies with or without RBD, but this has not yet been explored in iRBD. We sought to assess cholinergic neuronal integrity in iRBD using PET neuroimaging with the. The sample included 10 participants evenly divided between healthy subjects and patients with iRBD. Polysomnography and PET imaging with FEOBV were performed in all participants. Standardized uptake value ratios (SUVRs) were compared between the two groups using voxel wise t-tests. Non-parametric correlations were also computed in patients with iRBD between FEOBV uptake and muscle tonic and phasic activity during REM sleep.. Compared with healthy participants, significantly higher FEOBV uptakes were observed in patients with iRBD. The largest differences were observed in specific brainstem areas corresponding to the bulbar reticular formation, pontine coeruleus/subcoeruleus complex, tegmental periacqueductal grey, and mesopontine cholinergic nuclei. FEOBV uptake in iRBD was also higher than in controls in the ventromedial area of the thalamus, deep cerebellar nuclei, and some cortical territories (including the paracentral lobule, anterior cingulate, and orbitofrontal cortex). Significant correlation was found between muscle activity during REM sleep, and SUVR increases in both the mesopontine area and paracentral cortex.. We showed here for the first time the brain cholinergic alterations in patients with iRBD. As opposed to the cholinergic depletion described previously in RBD associated with clinical Parkinson's disease, increased cholinergic innervation was found in multiple areas in iRBD. The most significant changes were observed in brainstem areas containing structures involved in the promotion of REM sleep and muscle atonia. This suggests that iRBD might be a clinical condition in which compensatory cholinergic upregulation in those areas occurs in association with the initial phases of a neurodegenerative process leading to a clinically observable synucleinopathy.

Topics: Aged; Brain; Case-Control Studies; Cholinergic Neurons; Dementia; Female; Humans; Male; Middle Aged; Parkinson Disease; Piperidines; Polysomnography; Positron-Emission Tomography; REM Sleep Behavior Disorder; Sleep, REM; Synucleinopathies

The simultaneous use of dementia medications and anticholinergic medications occurs frequently. Cholinesterase inhibitors and anticholinergic medications likely counteract one another, potentially exposing patients to medications with decreased benefit, more adverse effects, and higher cost of care. We identified the rate of concurrent prescriptions of cholinesterase inhibitors/memantine with anticholinergics in an urban hospital setting with a large Asian and Pacific Islander population.. This study is a retrospective review of patients hospitalized from 1 January 2006 to 31 December 2010 at a general hospital who simultaneously received US Food and Drug Administration-approved dementia medications (galantamine, rivastigmine, donepezil, and/or memantine) and anticholinergics.. Overall, 304 patients receiving cholinesterase inhibitors/memantine also received anticholinergics. Of these patients, 64.1% were given high-potency anticholinergic medications, and 35.9% received medium-potency medications. Indications for the use of anticholinergic medication were urological (17.8%), gastrointestinal excluding nausea (32.6%), nausea (10.2%), psychiatric (7.9%), and other (31.6%). Asian patients received the combination of cholinesterase inhibitors/memantine and anticholinergics less frequently than Native Hawaiian or Caucasian patients (8.4% vs 12.2% and 13.3%, respectively; χ. Simultaneous prescribing of cholinesterase inhibitors, memantine, and anticholinergic medications was significantly less common than in previous studies, with some ethnic variability. The less frequent occurrence of concurrent medications in the Asian population may be because of variations in the rate of indications or in tolerability for anticholinergic medications among the population.

Topics: Aged; Aged, 80 and over; Asian People; Cholinergic Antagonists; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Galantamine; Hawaii; Hospitals, Urban; Humans; Indans; Male; Memantine; Native Hawaiian or Other Pacific Islander; Pacific Islands; Piperidines; Retrospective Studies; Rivastigmine

Topics: Acetaminophen; Aged; Aged, 80 and over; Automobile Driving; Cognition Disorders; Cognitive Dysfunction; Colonic Neoplasms; Delirium; Dementia; Donepezil; Early Detection of Cancer; Estrogen Replacement Therapy; Female; Geriatrics; Humans; Indans; Male; Neuropsychological Tests; Nootropic Agents; Oxycodone; Piperidines; Urinary Incontinence; Watchful Waiting

The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

Topics: Apolipoproteins E; Cholinesterase Inhibitors; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2D6; Dementia; Donepezil; Female; Follow-Up Studies; Humans; Indans; Male; Mental Status and Dementia Tests; Neuropsychological Tests; Piperidines; Polymorphism, Single Nucleotide; Time Factors

Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, and the cholinesterase inhibitor, donepezil, are approved in most countries for treating moderate-to-severe Alzheimer's disease (AD). These drugs have different molecular targets; thus, it is expected that the effects of combined treatment would be synergistic. Some reports do show memantine/donepezil synergy in ameliorating cognition in AD model animals, but their combined effects on behavioral and psychological symptoms of dementia (BPSD)-like behaviors have not been addressed. Here, we investigate combined memantine/donepezil effects on cognitive impairment and BPSD-like behaviors in olfactory bulbectomized (OBX) mice. Interestingly, combined administration synergistically improved both depressive-like behaviors and impaired social interaction in OBX mice, whereas only weak synergistic effects on cognitive performance were seen. To address mechanisms underlying these effects, we used in vivo microdialysis study and observed impaired nicotine-induced serotonin (5-HT) release in OBX mouse hippocampus. Combined memantine/donepezil administration, but not single administration of either, significantly antagonized the decrease in nicotine-induced 5-HT release seen in OBX mouse hippocampus. Furthermore, decreased autophosphorylation of calcium/calmodulin dependent protein kinase II (CaMKII) was rescued in hippocampal CA1 and dentate gyrus of OBX mice by combined memantine/donepezil administration. These results suggest that improvement of BPSD-like behaviors by the co-administration of both drugs is in part mediated by enhanced 5-HT release and CaMKII activity in OBX mouse hippocampus.

Topics: Animals; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Indans; Male; Maze Learning; Memantine; Mice; Olfactory Bulb; Piperidines; Random Allocation; Treatment Outcome

As with other types of dementia, the behavioral and psychological symptoms of dementia (BPSD) can make caregiving difficult for patients with dementia with Lewy bodies (DLB). We hypothesized that administration of donepezil at an increased dose of 10 mg/day might dose-dependently improve BPSD in DLB patients with relapse, after their symptoms had been controlled initially by donepezil therapy at the standard dose.. The present study was as an open-label trial. We enrolled 24 patients with DLB (diagnosed according to the Consortium on Dementia with Lewy Bodies Guideline-Revised) who experienced a relapse of BPSD despite treatment with donepezil at the standard dose (5 mg/day). The donepezil dose for these patients was increased to 10 mg/day, and we evaluated the efficacy and safety of this dose escalation strategy.. The Neuropsychiatric Inventory (NPI) scores for BPSD showed statistically significant improvements as a result of the increased dosage, except those for anxiety and euphoria, disinhibition, irritability/lability. High-dose donepezil therapy caused gastrointestinal symptoms in 4 patients, but there were no life-threatening adverse events, such as arrhythmias, or no exacerbation of parkinsonian symptoms.. We found that donepezil dose-dependently improved relapsing BPSD in these patients. Therefore, increasing the dosage of donepezil is a safe and effective treatment for patients with DLB who experience a relapse of BPSD.

Topics: Aged; Aged, 80 and over; Behavior; Behavioral Symptoms; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Indans; Lewy Body Disease; Male; Middle Aged; Piperidines; Severity of Illness Index; Treatment Outcome

Topics: Cholinesterase Inhibitors; Dementia; Female; Galantamine; Humans; Indans; Male; Phenylcarbamates; Piperidines; Pneumonia

Topics: Cholinesterase Inhibitors; Dementia; Female; Galantamine; Humans; Indans; Male; Phenylcarbamates; Piperidines; Pneumonia

To characterize pediatric exposures to the antidementia drugs donepezil, memantine, rivastigmine, and galantamine by reviewing a poison control system's database.. A retrospective review of a statewide poison control system's database identified cases of pediatric (less than 19 years of age) exposures to antidementia drugs over an 11-year period. Data collected included age, sex, drug(s) involved, route of exposure, reason for exposure, symptoms, and interventions.. There were 189 cases identified (53% male, median age: 2.3 years, 99% unintentional exposures). Donepezil was the most commonly reported exposure (106 cases), followed by memantine (57), galantamine (18), oral rivastigmine (16), and transdermal rivastigmine (3). Coingestants were reported in 68 (36%) cases. Symptoms were reported in 38 (20%) cases. Gastrointestinal symptoms were most common (n = 21) followed by central nervous system depression (n = 15). Oral rivastigmine was associated with higher rates of symptoms. No bradycardia, seizures, or fasciculations were reported. Eighty-nine cases (47%) were evaluated at a health care facility, and 13 (7%) were admitted to a hospital. Oral rivastigmine exposures were associated with increased rate of health care facility evaluation. Activated charcoal was administered in 28 cases. Atropine was given only once, for drooling. There were no serious outcomes or deaths in this series.. Reported pediatric exposures to antidementia drugs resulted in minimal morbidity and no mortality. Oral rivastigmine exposures were found to be associated with more symptoms and health care facility evaluations.

Topics: Child; Child, Preschool; Dementia; Donepezil; Female; Galantamine; Humans; Indans; Infant; Male; Memantine; Nootropic Agents; Piperidines; Poison Control Centers; Retrospective Studies; Rivastigmine

Nutritional status is one of the factors that affects disease progression, morbidity and mortality in elderly patients with dementia. The present study aimed to evaluate the effect of acetylcholinesterase inhibitor (AchEI) therapy on nutritional status and food intake in the elderly.. Newly diagnosed patients with dementia, who underwent comprehensive geriatric assessment (CGA) and were followed at regular intervals, were retrospectively evaluated. A total of 116 patients, who began to receive AchEI therapy and completed 6-month follow-up period under this treatment, were enrolled in the study.. Socio-demographic characteristics and data on comorbidity, polypharmacy, cognitive function, depression, activities of daily living and nutritional status (weight, Body Mass Index (BMI), Mini Nutritional Assessment (MNA)-Short Form) were recorded.. The mean age of the patients was 78.0±8.9 years. There was no significant difference between baseline and 6-month BMI, weight and MNA scores of dementia patients who received AchEI therapy (p>0.05). With regard to the relation between changes in BMI, weight and MNA on the 6th month versus baseline, and donepezil, rivastigmine and galantamine therapies, no difference was determined (p>0.05). However, no worsening in food intake was observed (kappa: 0.377). When the effects of each AchEI on food intake were compared, food intake in rivastigmine treated patients was not decreased as much as it was in galantamine or donepezil treated patients (p<0.05).. AchEI therapy has no unfavorable effect on nutritional status or weight in elderly patients with different types of dementia, but it seems that food intake is better in those treated by rivastigmine patch.

Topics: Acetylcholinesterase; Activities of Daily Living; Aged; Body Mass Index; Body Weight; Cholinesterase Inhibitors; Dementia; Disease Progression; Donepezil; Eating; Female; Follow-Up Studies; Galantamine; Geriatric Assessment; Humans; Indans; Male; Nutrition Assessment; Nutritional Status; Piperidines; Polypharmacy; Retrospective Studies; Rivastigmine

In spite of the increase in the number of patients with dementia in countries with older population, basic epidemiologic data are still scarce. The objective of this paper is to investigate pharmacoepidemiological characteristics of treatment of dementia in Croatia, and to present them in the context of certain epidemiological characteristics that illustrate the growing pressure this disease exerts on the healthcare system.. Data on medication utilization were taken from Croatian Health Insurance Fund (HZZO) and Agency for Medicinal Products and Medical Devices of Croatia (HALMED). Data on the number of hospital stays were supplied by Croatian Institute of Public Health (HZJZ). Internal data on the number of outpatient examinations from the Clinical hospital "Sveti Duh" were used as well.. In the observed period (2012-2014), 4568 patients were treated with anti-dementia medications, of which 1275 (32%) with donepezil, and 2753 (68%) with memantine. According to HALMED, the utilization of those medications is constantly increasing, and has increased manifold from 2005 to 2014. The estimate of the proportion of treated patients with dementia aged 60 years and over is around 9.2%. The number of dementia-related hospital stays is also increasing, and has increased by 9.6% in the last 5-year period, compared to the preceding 5-year period. The number of outpatient examinations in Clinical Hospital "Sveti Duh" grew from 351 in 2007 to 1151 in 2015 (January 1(st) - October 26(th)).. The strain this condition exerts on the healthcare system is increasing yearly. In spite of the large increase in the medication utilization over the previous years, the proportion of treated patients is still small, and further increase in their use is to be expected. It is necessary to monitor this in the years ahead.

Topics: Adult; Aged; Aged, 80 and over; Croatia; Databases, Factual; Dementia; Donepezil; Dopamine Agents; Female; Hospitalization; Humans; Indans; Male; Memantine; Middle Aged; Nootropic Agents; Pharmacoepidemiology; Piperidines; Young Adult

Patients suffering from Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies can be treated well with the cholinesterase inhibitors rivastigmine or donepezil, and because of the increasing number of these patients undergoing surgery in general anaesthesia we find it urgent to draw attention to possible complications such as severe bradycardia or third-degree heart block when propofol and remifentanil are being used.

Topics: Aged; Anesthesia, General; Anesthetics, Intravenous; Bradycardia; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Humans; Indans; Male; Piperidines; Propofol; Remifentanil

The purpose of the study was to evaluate the influences of cholinesterase inhibitors on sleep pattern and sleep disturbance. A total of 87 mild to moderate stage dementia patients who were not on cholinesterase enzyme inhibitor and memantine treatment were included in the study. The dementia patients were treated with donepezil, galantamine or rivastigmine, depending on the preference of the clinician. Fifty-five dementia patients (63.2 %) completed the study. Twenty-three elderly subjects, who had normal cognitive functions, were included in the study as the control group. The Pittsburgh Sleep Quality Index was used for evaluating the sleep quality at the beginning and at the final assessment. The improvement in sleep quality was better with regard to changes in Pittsburgh Sleep Quality Index scores with galantamine treatment compared to the donepezil and the control groups. A significant decrease in Pittsburgh Sleep Quality Index scores was detected in the galantamine group after treatment. Although statistically not significant, rivastigmine decreased and donepezil increased the Pittsburgh Sleep Quality Index scores after treatment. Dementia patients who had a poor sleep quality (n: 36), the rate of improvement in sleep disturbance was 81.8 % in the galantamine group, 75 % in the rivastigmine, and 50 % in the donepezil group. Galantamine may be the first choice of cholinesterase inhibitor in mild to moderate dementia patients in terms of improving sleep quality.

Topics: Aged; Aged, 80 and over; Chi-Square Distribution; Cholinesterase Inhibitors; Dementia; Donepezil; Dose-Response Relationship, Drug; Female; Galantamine; Humans; Indans; Male; Piperidines; Rivastigmine; Severity of Illness Index; Sleep Wake Disorders; Treatment Outcome

Results from various studies indicate that the presence of certain heavy metals such as aluminum (Al), arsenic (As), copper (Cu), lead (Pb), and mercury (Hg) may enhance the aggregation of Aβ and oxidative stress levels leading to neuronal toxicity and Alzheimer's disease (AD). Studies also reveal that anomalous brain copper-cholesterol (Cu-Ch) homeostasis may lead to memory deficits in Swiss albino mice.. The present study investigates the anti-amnesic potential of clioquinol (5-chloro-7-iodoquinolin-8-ol) in cognitive deficits associated with experimental dementia induced by Cu-Ch.. Administration of Cu-Ch {0.21 mg/kg, per os - 2% w/v, per os for 8 weeks} was used to induce dementia in Swiss albino mice. The Morris water maze (MWM) test was performed to assess the effect on learning and memory. A battery of biochemical estimations was performed following the MWM test such as brain-reduced glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS), acetylcholinestrase (AChE) activity, and serum cholesterol levels.. Administration of Cu-Ch produced a marked decline in MWM performance measured during the acquisition (78.9 ± 3.3) and retrieval trials (9.5 ± 2.4), reflecting impairment of learning and memory. Cu-Ch-treated mice also exhibited a marked accentuation of AChE activity (5.8 ± 0.55) and TBARS levels (9.74 ± 1.9) along with a decline in the GSH level (15.4 ± 3.3) and the SOD level (26 ± 2.5) when compared with the untreated control group. Administration of clioquinol significantly attenuated Cu-Ch-induced memory deficits and biochemical alterations.. The findings demonstrate memory restorative ability of clioquinol which may be attributed to its anti-cholinesterase, antioxidative, and cholesterol-lowering potential.

Topics: Acetylcholinesterase; Animals; Anticholesteremic Agents; Antioxidants; Behavior, Animal; Biomarkers; Brain; Cholesterol; Cholinesterase Inhibitors; Clioquinol; Copper; Dementia; Disease Models, Animal; Donepezil; Female; Glutathione; GPI-Linked Proteins; Indans; Male; Maze Learning; Memory; Mice; Nootropic Agents; Oxidative Stress; Piperidines; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Time Factors

Continuous treatment is an important indicator of medication adherence in dementia. However, long-term studies in larger clinical settings are lacking, and little is known about moderating effects of patient and service characteristics.. Data from 12,910 outpatients with dementia (mean age 79.2 years; SD = 7.6 years) treated between January 2003 and December 2013 in Germany were included. Continuous treatment was analysed using Kaplan-Meier curves and log-rank tests. In addition, multivariate Cox regression models were fitted with continuous treatment as dependent variable and the predictors antidementia agent, age, gender, medical comorbidities, physician specialty, and health insurance status.. After one year of follow-up, nearly 60% of patients continued drug treatment. Donezepil (HR: 0.88; 95% CI: 0.82-0.95) and memantine (HR: 0.85; 0.79-0.91) patients were less likely to be discontinued treatment as compared to rivastigmine users. Patients were less likely to be discontinued if they were treated by specialist physicians as compared to general practitioners (HR: 0.44; 0.41-0.48). Younger male patients and patients who had private health insurance had a lower discontinuation risk. Regarding comorbidity, patients were more likely to be continuously treated with the index substance if a diagnosis of heart failure or hypertension had been diagnosed at baseline.. Our results imply that besides type of antidementia agent, involvement of a specialist in the complex process of prescribing antidementia drugs can provide meaningful benefits to patients, in terms of more disease-specific and continuous treatment.

Topics: Age Factors; Aged; Aged, 80 and over; Databases, Factual; Dementia; Donepezil; Female; Germany; Humans; Indans; Kaplan-Meier Estimate; Male; Memantine; Middle Aged; Nootropic Agents; Piperidines; Practice Patterns, Physicians'; Retrospective Studies

To compare the risk of pneumonia in older adults receiving donepezil, galantamine, or rivastigmine for dementia.. Retrospective cohort study.. Nationally representative 5% sample of Medicare databases.. Medicare beneficiaries aged 65 and older who newly initiated cholinesterase inhibitor therapy between 2006 and 2009.. Pneumonia, defined as the presence of a diagnosis code for pneumonia as the primary diagnosis on an inpatient claim or on an emergency department claim followed by dispensing of appropriate antibiotics. Cox proportional hazards models were used to estimate the risk of pneumonia. Subgroup analyses and sensitivity analyses were conducted using alternative pneumonia definitions and adjustments using high-dimensional propensity scores to test the robustness of the results.. The mean age of 35,570 new users of cholinesterase inhibitors (30,174 users of donepezil, 1,176 users of galantamine, 4,220 users of rivastigmine) was 82; 75% were women, and 82% were white. The cumulative incidence of pneumonia was 51.9 per 1,000 person-years. The risk of pneumonia for rivastigmine users was 24% lower than that of donepezil users (hazard ratio (HR)=0.75, 95% confidence interval (CI)=0.60-0.93). Risk in galantamine users (HR=0.87, 95% CI=0.62-1.23) was not significantly different from risk in donepezil users. Results of subgroup and sensitivity analyses were similar to the primary results.. The risk of pneumonia was lower in individuals receiving rivastigmine than in those receiving donepezil. Additional studies are needed to confirm the findings of pneumonia risk between the oral and transdermal forms of rivastigmine and in users of galantamine.

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Cohort Studies; Dementia; Donepezil; Female; Galantamine; Humans; Indans; Male; Phenylcarbamates; Piperidines; Pneumonia; Retrospective Studies; Risk Assessment; Rivastigmine

Cholinesterase inhibitors are used to treat the symptoms of dementia and can theoretically cause bradycardia. Previous studies suggest that patients taking these medications have an increased risk of undergoing pacemaker insertion. Since these drugs have a marginal impact on patient outcomes, it might be preferable to change drug treatment rather than implant a pacemaker. This population-based study determined the association of people with dementia exposed to cholinesterase inhibitor medication and pacemaker insertion.. We used data from the Ontario health administrative databases from January 1, 1993 to June 30, 2012. We included all community-dwelling seniors who had a code for dementia and were exposed to cholinesterase inhibitors (donezepil, galantamine, and rivastigmine) and/or drugs used to treat co-morbidities of hypertension, diabetes, depression and hypothyroidism. We controlled for exposure to anti-arrhythmic drugs. Observation started at first exposure to any medication and continued until the earliest of pacemaker insertion, death, or end of study.. 2,353,909 people were included with 96,000 (4.1%) undergoing pacemaker insertion during the observation period. Case-control analysis showed that pacemaker patients were less likely to be coded with dementia (unadjusted OR 0.42 [95%CI 0.41-0.42]) or exposed to cholinesterase inhibitors (unadjusted OR 0.39 [95%CI 0.37-0.41]). That Cohort analysis showed patients with dementia taking cholinesterase inhibitors had a decreased risk of pacemaker insertion (unadj-HR 0.58 [0.55-0.61]). Adjustment for patient age, sex, and other medications did not notably change results, as did restricting the analysis to incident users.. Patients taking cholinesterase inhibitors rarely undergo, and have a significantly reduced risk of, cardiac pacemaker insertion.

Topics: Aged; Cholinesterase Inhibitors; Comorbidity; Databases, Factual; Dementia; Donepezil; Female; Galantamine; Health Services Research; Humans; Indans; Male; Ontario; Pacemaker, Artificial; Piperidines; Prosthesis Implantation; Retrospective Studies; Risk; Rivastigmine

Dementia networks in Germany constitute a specialised setting for integrated dementia care and have shown benefits on relevant outcomes, including those of drug treatment. National guidelines recommend treatment with acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) or the N-Methyl-D-Aspartate antagonist (memantine) to reduce cognitive symptoms. However, prescription rates are lower than 30 % in general practises. This study aims to describe antidementia drug treatment and the factors that are associated with the treatment in different dementia networks across Germany.. We have analysed the socio-demographic, clinical and utilisation data from 560 patients with dementia (PWD), as well as data from their caregivers, in 13 selected dementia networks in Germany. The patients and caregivers were interviewed in their homes or in the network facilities. Multiple logistic regression models were fitted to evaluate the socio-demographic and clinical factors associated with the utilisation of antidementia drug treatment in the various networks.. In all of the networks in the study, 52 % of the participants received an antidementia drug treatment. Factors associated with the utilisation of the antidementia drug treatment were: formal diagnosis (OR = 16.81, p < 0.001), association with a physician in the network (OR = 3.69, p < 0.001), higher number of comorbidities (OR = 0.88, p = 0.039), living alone (OR = 0.51, p = 0.032) and higher age (OR = 2.97, p = 0.002).. Medical treatment of PWD with antidementia drugs in dementia networks in Germany is more frequent than in primary and nursing home care settings. Our findings also suggest that participants with a formal diagnosis and a physician in the network have increased rates of receiving antidementia drug treatments. These findings suggest that dementia networks focusing on medical treatment should support diagnostic procedures and incorporate physician specialists.

Topics: Aged; Aged, 80 and over; Caregivers; Cholinesterase Inhibitors; Dementia; Donepezil; Dopamine Agents; Female; Galantamine; Germany; Humans; Indans; Interviews as Topic; Logistic Models; Male; Memantine; Neuroprotective Agents; Nootropic Agents; Piperidines; Rivastigmine

Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study.. To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study.. 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated.. The median survival time was 3.39 years (95% confidence interval [CI]: 2.88-3.79) for VaD without medication, 6.62 years (95% CI: 6.24-7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85-3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30-8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73-6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02-9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55-2.83) without medication, 1.46 (95% CI: 1.39-1.54) with nootropics, 1.05 (95% CI: 0.82-1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80-1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15-1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22-2.72).. Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.

Topics: Cohort Studies; Dementia; Dihydroergocristine; Dihydroergotamine; Donepezil; Galantamine; Humans; Indans; Memantine; Neuroprotective Agents; Nootropic Agents; Piperidines; Piracetam; Proportional Hazards Models; Retrospective Studies; Rivastigmine; Taiwan; Time Factors

Topics: Arrhythmias, Cardiac; Cholinesterase Inhibitors; Dementia; Donepezil; Electrocardiography; Female; Humans; Indans; Middle Aged; Piperidines

This survey analyzes two national pharmacovigilance databases in order to determine the major adverse reactions observed with the use of cholinesterase inhibitors in dementia. We conducted a statistical analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction Database (CVARD) concerning the side effects of cholinesterase inhibitors. The statistics calculated for each adverse event were the frequency and the reporting odds ratios (ROR). A total of 9877 and 2247 reports were extracted from the FAERS and CVARD databases, respectively. A disproportionately higher frequency of reports of death as an adverse event for rivastigmine, compared to the other acetylcholinesterase inhibiting drugs, was observed in both the FAERS (ROR = 3.42; CI95% = 2.94-3.98; P<0.0001) and CVARD (ROR = 3.67; CI95% = 1.92-7.00; P = 0.001) databases. While cholinesterase inhibitors remain to be an important therapeutic tool against Alzheimer's disease, the disproportionate prevalence of fatal outcomes with rivastigmine compared with alternatives should be taken into consideration.

Topics: Adverse Drug Reaction Reporting Systems; Alzheimer Disease; Canada; Cholinesterase Inhibitors; Databases, Factual; Dementia; Donepezil; Galantamine; Humans; Indans; Pharmacovigilance; Piperidines; Rivastigmine; United States; United States Food and Drug Administration

Combinatorial therapy directed at both vascular and neurodegenerative aspects of dementia may offer a promising strategy for treatment of dementia, which often has a multifactorial basis in the elderly. We investigated whether the phosphodiesterase III inhibitor cilostazol, which is often used in the prevention of stroke and peripheral artery disease, may delay cognitive decline in the elderly receiving donepezil.. Medical records were retrospectively surveyed to identify patients who had received donepezil for more than one year and had undergone Mini-Mental State Examination (MMSE) at least at two time points. Those with an initial MMSE score of less than 27 points were subjected to analysis (n = 156), with a cut-point of 21/22 applied to assign them to mild (n = 70) and moderate/severe (n = 86) dementia. The change of total MMSE score per year was compared between patients who had received donepezil and those given both donepezil and cilostazol.. In patients with mild dementia who had received donepezil and cilostazol (n = 34; 77.2±6.8 years old), the annual change in MMSE score was -0.5±1.6 during an observational period of 28.6±11.7 months, with those receiving donepezil only (n = 36; 78.4±6.5 years old) scoring less (-2.2±4.1) during 30.4±12.8 months with a statistical intergroup difference (p = 0.022). Multivariate analysis showed that absence of cilostazol treatment was the only significant predictor of MMSE decline. A positive effect of cilostazol was found in three subscale scores of MMSE, orientation for time or place and delayed recall. By clear contrast, in patients with moderate/severe dementia, there were no intergroup differences in decrease of total or subscale MMSE scores between the two groups.. These results suggest potential for cilostazol treatment in the suppression of cognitive decline in patients receiving donepezil with mild dementia but not in those with moderate/severe dementia.

Topics: Aged; Cholinesterase Inhibitors; Cilostazol; Dementia; Donepezil; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Indans; Male; Neuroprotective Agents; Neuropsychological Tests; Piperidines; Prognosis; Retrospective Studies; Tetrazoles

Although several case reports suggested that donepezil hydrochloride can induce bradycardia or atrioventricular block, the details remain unclear. We implemented a study of the impact of donepezil hydrochloride administration on PR, RR, and QT intervals.. The subjects were 18 patients who were diagnosed with either dementia or cognitive disorder (DSM-IV-TR) and were hospitalized between January 2011 and December 2012. After hospitalization, they were treated with donepezil hydrochloride. Clinical parameters and electrocardiograms before and after the administration of donepezil hydrochloride were retrieved from the patients' medical records.. After the administration of donepezil hydrochloride, the mean PR interval significantly increased from 177.3 ± 30.9 to 186.8 ± 38.4 ms (p<0.001). And the mean RR interval also significantly increased from 850.3 ± 112.5 to 886.7 ± 136.4 ms (p=0.014). The mean difference in the PR interval before and after the administration of donepezil hydrochloride was 9.5 ± 17.1 (range=-21.0-44.0) ms. The QT intervals were unaffected by the administration of donepezil hydrochloride.. Care should be taken when administering donepezil to patients with atrioventricular block, or patients taking other drugs that can prolong the PR interval. Copyright © 2014 John Wiley & Sons, Ltd.

Topics: Aged; Cognition Disorders; Dementia; Donepezil; Electrocardiography; Female; Heart; Humans; Indans; Male; Nootropic Agents; Piperidines

The benefits of escalating the dose of donepezil in patients who are already receiving long-term treatment with it have not been well evaluated. Therefore, an exploratory study to assess the effects of donepezil dose escalation in patients with Parkinson's disease with dementia, and specifically on patients receiving long-term treatment with donepezil, was performed.. Patients treated with 5-mg/day donepezil for at least 3 months and having a Mini-Mental State Examination (MMSE) score between 10 and 26 were included in this study. Donepezil dosage was then increased to 10 mg/day for 12 weeks. The outcome measures were a modified form of the Neuropsychiatric Inventory (NPI) with an extra domain for additional evaluation of fluctuation in cognitive functions (NPI-11) and the MMSE.. Of the nine patients enrolled, two withdrew because of nausea and inability to be assessed on the predetermined date; this left seven participants (four men and three women) with a mean age of 74.6 ± 6.9 years, a mean period of Parkinson's disease of 11.7 ± 7.5 years, and median donepezil use of 7 months (range: 3-56 months). At baseline, the mean total NPI-11 and mean MMSE scores were 18.3 ± 5.6 points and 21.3 ± 5.3 points, respectively. At week 12, they improved by 8.3 points (P < 0.01) and 3.0 points (P = 0.08), respectively, from the baseline. The NPI symptom domains that improved by 1 or more points were hallucination (1.3 points), depression (1.0 points), anxiety (1.6 points), and aberrant motor behaviour (1.7 points). None of the patients withdrew because of worsening of parkinsonism.. The present results suggest that treatment with dose escalation of donepezil from 5 mg/day to 10 mg/day may be therapeutically useful for patients with Parkinson's disease with dementia who have taken donepezil 5 mg/day in the long term.

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Indans; Long-Term Care; Male; Middle Aged; Parkinson Disease; Piperidines; Prospective Studies; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Patients with dementia are thought to be more sensitive to anesthesia, although volatile anesthetic requirement has not specifically been evaluated in this population. We tested the hypothesis that patients with dementia having non-cardiac surgery have a lower ratio of bispectral index (BIS) to minimal alveolar concentration (MAC) during the five minutes immediately preceding incision, thus exhibiting deeper hypnotic levels at a given MAC fraction.. We obtained records from our database registry on patients who had volatile general anesthesia during their most recent operation. We excluded patients premedicated with midazolam. Patients with dementia were identified and their diagnosis was confirmed by chart review. Each patient with dementia was successfully matched with a maximum of five patients without dementia using a multivariate nearest-neighbor distance-matching algorithm restricted to the following criteria: American Society of Anesthesiologists physical status, age, five-minute pre-incision time-weighted average (TWA) estimated effect-site concentration of propofol and fentanyl, and use of remifentanil. Our primary outcome was the TWA BIS-to-MAC ratio during the five minutes immediately preceding incision.. We analyzed 31 patients with dementia matched with 151 patients without dementia. Median [quartiles] TWA BIS-to-MAC ratios for the matched patients were 85 [73, 100] for the patients with dementia and 78 [73, 84] for the patients without dementia. The percent difference in mean BIS-to-MAC ratios between patients with dementia and patients without dementia was 9% (95% confidence interval: -9% to 29%) (P = 0.35, Wald test).. Our results do not support the hypothesis that patients with dementia are more sensitive to volatile anesthetics than patients without dementia.

Topics: Aged; Aged, 80 and over; Anesthesia, General; Anesthetics, Inhalation; Case-Control Studies; Consciousness Monitors; Dementia; Fentanyl; Humans; Middle Aged; Multivariate Analysis; Piperidines; Propofol; Remifentanil; Retrospective Studies

Topics: Aged; Dementia; Donepezil; Galantamine; Hospitalization; Hospitals, Psychiatric; Humans; Indans; Nootropic Agents; Phenylcarbamates; Piperidines; Rivastigmine

Cholinesterase inhibitors can delay the progression of Alzheimer's disease (AD). Several clinical trials of the drug in moderate to severe AD have consistently reported clinically positive effects. A combining effect with psychosocial intervention was reported in mild to moderate AD patients. Since a therapeutic approach or rehabilitation combined with cholinesterase inhibitors for severe AD patients remains controversial, we performed a prospective intervention for patients in Long-Term Care Health Facilities (LTCHF).. Two LTCHFs (N1, N2) were enrolled. N1 is a 126-bed facility that does not treat with donepezil but rather with psychosocial intervention (reality orientation and reminiscence). N2 is a 150-bed facility with a 50-bed special dementia unit, in which the physician can prescribe donepezil. On top of the similar psychosocial intervention, rehabilitation is performed in N2. Thirty-two severe AD patients (MMSE < 6) in N1 and N2 (16 vs. 16) were compared for the effect of donepezil (10 mg/d for 3 months) with or without psychosocial intervention (n = 8 vs. 8 for each facility). The Vitality Index was used to assess daily activities and the introduction of rehabilitation.. The response ratio (MMSE 3+) of donepezil was 37.5% in N2. The combination of donepezil with the psychosocial intervention improved the Vitality Index total score, and Communication, Eating, and Rehabilitation subscores (Wilcoxon, p = 0.016, 0.038, 0.023, and 0.011, respectively). Most of them were smoothly introduced to rehabilitation, and the proportion of accidental falls decreased. Psychosocial intervention in N1 without the drug only improved the total score (Wilcoxon, p = 0.046).. A combined therapeutic approach of donepezil and psychosocial intervention can have a positive effect, even for severe patients through the introduction of rehabilitation and decreasing accidental falls. However, these findings require replication in a larger cohort.

Topics: Activities of Daily Living; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Disease Progression; Donepezil; Female; Humans; Indans; Long-Term Care; Male; Nursing Homes; Piperidines; Prospective Studies; Severity of Illness Index; Treatment Outcome

It is largely unknown how the medical treatment of patients diagnosed with dementia is followed up in primary care. Therefore, we studied patient medical records from two dementia clinics and from the referring primary care centres.. A retrospective study of 241 patients was conducted from April to October 2011 in north west Stockholm, Sweden. Over half (51.5%) of the patients had Alzheimer's disease (AD), the remainder had mixed AD/vascular dementia (VaD). Eighty-four medical reports from primary care (35% of the study group) were analysed at follow-up 18 months after diagnosis.. All four dementia drugs available on the Swedish market (three cholinesterase inhibitors [donepezil, rivastigmine and galantamine] and memantine) were prescribed at the two dementia clinics. The most commonly used dementia drug was galantamine. There were differences between the two dementia clinics in preference and combination of drugs and of treatment given to male and female patients. At follow-up, 84% were still on dementia medication. Drug use was followed up by the general practitioners (GPs) in two-thirds of the cases. Eighteen per cent of the GPs' medical records made no reference to the patient's dementia or treatment even though dementia drugs were included in the list of medications prescribed.. The results indicate that the Swedish guidelines for treatment of cognitive symptoms in AD are being followed in primary care. However, documentation of follow-up of drug treatment was sometimes insufficient, which calls for development of guidelines for complete medical records and medication lists.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Dementia; Dementia, Vascular; Donepezil; Female; Galantamine; Humans; Indans; Male; Medical Records; Memantine; Nootropic Agents; Phenylcarbamates; Piperidines; Practice Guidelines as Topic; Practice Patterns, Physicians'; Primary Health Care; Retrospective Studies; Rivastigmine; Sweden; Treatment Outcome

Cognitive impairment and dementia treatment costs are significant for health systems. According to national and international guidelines, recommended drugs for treatment of dementias are cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. Despite these guidelines recommendations, other nootropics, vasodilators and antioxidants are often used in Argentina. The purpose of this study was to describe and compare the prescription pattern of commonly used drugs for the treatment of cognitive disorders and dementia in different regions of Argentina. An observational, retrospective study of 1814108 recipes prescribed to National Institute of Social Services for Retired and Pensioners outpatients during the during the second half of 2008 and the first and second half of 2009 was performed, taking in count the whole country and also different Argentina's regions. Demographic variables, quantity and rate of prescriptions, dosage forms and strengths were analyzed. Considering the entire country, memantine was the most prescribed drug in these periods (570893 packages). An increase in the memantine, donepezil, rivastigmine and idebenone rates of prescription was observed. Prescription rate of memantine increased in the North-West and North-East regions, that of idebenone in the North-East region and Patagonia and donepezil in the North-East region. Non recommended drugs were highly prescribed in all the analyzed regions. Some of them were indicated to young and middle-aged patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Argentina; Child; Child, Preschool; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Dementia, Vascular; Donepezil; Drug Prescriptions; Female; Galantamine; Humans; Indans; Infant; Male; Memantine; Middle Aged; Phenylcarbamates; Piperidines; Retrospective Studies; Rivastigmine; Young Adult

(i) To describe patient and public involvement (PPI) in a network promoting research in dementia and neurodegenerative diseases, in terms of activity at the different stages of the research cycle and within the different levels of the research network. (ii) To use case studies to try and answer the question: what benefits (if any) does PPI in research bring to the research process?. PPI in health research is a central part of government policy, but the evidence base underpinning it needs strengthening. PPI allows exploration of feasibility, acceptability and relevance of hypotheses, assists in the precise definition of research questions and increases accrual to studies. However, the measurement of outcomes is methodologically difficult, because the impact of lay researchers may occur through team interactions and be difficult to untangle from the efforts of professional researchers. Opportunities for PPI in rapidly progressive diseases may be limited, and involvement of people with marked cognitive impairment is particularly challenging.. (i) Description of PPI within the DeNDRoN network. (ii) Case studies of three research projects which asked for extra help from centrally organized PPI.. PPI in research projects on the DeNDRoN portfolio may function at different levels, occurring at project, local research network and national level. Case studies of three research projects show different roles for PPI in research and different functions for centrally organized PPI, including contribution to remedial action in studies that are not recruiting to target, solving problems because of the complexity and sensitivity of the research topic, and linking researchers to PPI resources.. The case studies suggest that centrally organized PPI can have 'diagnostic' and remedial functions in studies that are struggling to recruit and serve as reinforcement for study-level PPI in the complex and sensitive research topics that are typical in neurodegenerative diseases research. PPI may be actively sought by researchers, but the infrastructure of PPI is not yet so widespread in the research community that lay researchers are easy to find; a centrally organized PPI resource can assist in this situation.

Topics: Alzheimer Disease; Biomedical Research; Community Participation; Dementia; Donepezil; Humans; Indans; Memantine; Neurodegenerative Diseases; Nootropic Agents; Organizational Case Studies; Patient Participation; Piperidines

Topics: Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Dyskinesia, Drug-Induced; Female; Humans; Indans; Neck Muscles; Parkinson Disease; Piperidines; Posture

A novel, simple, specific and sensitive high performance liquid chromatography (HPLC) assay for the detection and quantification of donepezil in serum of demented patients has been developed and validated. The analytical procedure involves an offline serum preextraction using solid phase extraction (SPE) cartridges (Oasis® HLB, Waters Co). The chromatographic analyses were performed on a Dionex HPLC system with a Phenomenex Luna Phenyl-Hexyl analytical column, and a mobile phase with the two components 0.02 mol/l phosphate buffer and acetonitrile. The flow rate was 0.4 ml/min. For the detection of donepezil three different UV wavelengths were used as an interference-control check. Interference tests between donepezil and 100 of the most commonly used concomitant medications allow quantification of donepezil under the polypharmaceutical conditions of the daily clinical routine. The retention time for donepezil was 12.1 min. The method was validated according to the guidelines of the Society of Toxicology and Forensic Chemistry (GTFCh): The calibration curve was linear over a concentration range from 5 to 160 ng/ml (n=8/r²>0.999). No endogenous compounds were found to interfere with the analyte, which was shown by retention times for the comedication most often prescribed to demented patients. The method had an accuracy of >85%. Intra- and inter-assay coefficients of variation were <6% and <8%, respectively, at three different concentrations. The limit of quantification (LOQ) and the limit of detection (LOD) were found to be 6.1 and 1.7 ng/ml for donepezil. Application of the method to patient serum samples discovered that concentrations suggested as "therapeutic" in the literature may only be reached either by high, off-label dosages or by utilization of inhibitory metabolic effects of the comedication.

Topics: Chromatography, High Pressure Liquid; Dementia; Donepezil; Drug Monitoring; Drug Stability; Humans; Indans; Linear Models; Piperidines; Polypharmacy; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction; Spectrophotometry, Ultraviolet

We describe a 62-year-old female diagnosed with Alzheimer's disease, who had been treated with donepezil for approximately 1 year. When she developed a low-grade fever and digestive complaints, her family physician interpreted these symptoms as side effects of the drug and ordered donepezil to be discontinued. Not only was there no improvement of the somatic symptoms after discontinuation of donepezil, but there was also a worsening of the dementia symptoms, culminating in delirium. When donepezil was re-prescribed, the delirium resolved and the patient's mental state stabilized. The authors urge great caution in discontinuing treatment with acetylcholinesterase inhibitors such as donepezil.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Delirium; Dementia; Donepezil; Female; Humans; Indans; Middle Aged; Piperidines; Substance Withdrawal Syndrome; Withholding Treatment

Pisa syndrome or pleurothotonus is the persistent flexion of the body and head to one side giving the appearance of the leaning tower of Pisa. It is most commonly caused by typical and atypical antipsychotic drugs. We report a case of Pisa Syndrome caused by prolonged use of high dose cholinesterase inhibitor, rivastigmine. Symptoms subsided when rivastigmine was withdrawn and did not reappear when a different cholinesterase inhibitor, donepezil was introduced. Physicians should be aware of Pisa syndrome and should alert patient of this possibility when starting and stepping up medications. The purpose of reporting this case is to create awareness among general practitioners as it is a reversible condition which responds to removal of the offending drug.

Topics: Aged; Benzodiazepines; Cholinesterase Inhibitors; Delusions; Dementia; Donepezil; Humans; Indans; Male; Movement Disorders; Olanzapine; Phenylcarbamates; Piperidines; Posture; Rivastigmine; Syndrome

A survey was conducted among pharmacists providing "home-visit guidance on drug management" to patients taking medication for dementia. Factors related to medication adherence among patients and pharmacists' acquisition of patient information were then verified. The survey items were: (1) patient attributes (degree of care received, bed-ridden, family composition, and living environment); (2) the person controlling medications; (3) drug storage method and location; (4) dispensing method; (5) patient management of visiting nurses; (6) patient management of visiting physician; (7) details of pharmacist's home-visit guidance; (8) medication adherence; (9) five items related to cognitive function (short-term memory, autonomous judgment, fluctuations in level of consciousness, excitation and loss of orientation, understanding); and (10) ten items related of ADL (mobility in bed, transferring, mobility within the home or outdoors, dressing upper/lower body, eating, toilet use, individual hygiene, bathing). The t test was used to verify the number of items of patient information concerning cognitive function and physical function that pharmacists could acquire at a visit. It was suggested that pharmacists were able to acquire more patient information (①cognitive function and ②ADL) when they visited patients cared for at home, compared to facility residents (①p=0.008, ② p=0.006). Thus, it was suggested that there is a latent risk concerning the pharmacist's ability to discover problems with administration of medications among facility residents. These findings demonstrate that it is essential for pharmacists to be more proactive about providing home-visit guidance.

Topics: Activities of Daily Living; Cognition; Dementia; Donepezil; Health Facilities; House Calls; Humans; Indans; Nootropic Agents; Patient Care Management; Patient Compliance; Pharmacists; Pilot Projects; Piperidines; Professional Role

Although donepezil, an acetylcholinesterase inhibitor, has been proved to be effective in ameliorating cognitive impairment in Parkinson's disease with dementia (PDD), the responsiveness of patients to donepezil therapy varies. [5-(11)C-methoxy]donepezil, the radiolabeled form of donepezil, is a ligand for positron emission tomography (PET), which can be exploited for the quantitative analysis of donepezil binding to acetylcholinesterase and for cholinergic imaging.. To investigate the deficits of the cholinergic system in the brain in PDD and its association with response to donepezil therapy.. Twelve patients with PDD and 13 normal control subjects underwent [5-(11)C-methoxy]donepezil-PET imaging. For patients with PDD, daily administration of donepezil was started after [5-(11)C-methoxy]donepezil-PET imaging and continued for 3 months.. In the PDD group, the mean total distribution volume of the cerebral cortices was 22.7% lower than that of the normal control group. The mean total distribution volume of the patients with PDD was significantly correlated with improvement of visuoperceptual function after 3 months of donepezil therapy.. The results suggest that donepezil therapy is more effective in patients with less decrease in acetylcholinesterase, a binding site of donepezil, at least in the specific cognitive domain.

Topics: Aged; Antiparasitic Agents; Brain Mapping; Case-Control Studies; Cholinergic Agents; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Indans; Male; Mental Status Schedule; Middle Aged; Parkinson Disease; Piperidines; Positron-Emission Tomography

To compare the cardiovascular safety of currently marketed dementia medications in new users in the United States and Denmark.. Retrospective cohort study.. Nationally representative sample of Medicare beneficiaries from 2006 through 2009 and nationwide Danish administrative registries from 1997 through 2007.. Individuals treated with a dementia medication aged 65 and older.. Hospitalizations for myocardial infarction (MI), heart failure, and syncope or atrioventricular block in both cohorts; fatal or nonfatal MI and cardiac death in the Danish cohort; and all-cause mortality in sensitivity analyses.. In 46,737 Medicare beneficiaries and 29,496 Danish participants, donepezil was the most frequently used medication. There were no substantial differences in the risk of MI or heart failure between participants using donepezil and those using other cholinesterase inhibitors (all hazard ratios (HR) crossing 1). In the Danish cohort, memantine was associated with fatal or nonfatal MI (HR = 1.33, 95% confidence interval (CI) = 1.08-1.63), cardiac death (HR = 1.31, 95% CI = 1.12-1.53), and a trend toward higher rates of hospitalization for MI (HR = 1.31, 95% CI = 0.98-1.76). Memantine was also associated with greater risk of all-cause mortality in the Medicare (HR = 1.20, 95% CI = 1.13-1.28) and Danish (HR = 1.83, 95% CI = 1.73-1.94) cohorts, suggesting that sicker individuals were selected for memantine therapy.. Cholinesterase inhibitors have similar cardiovascular risk profiles. Associations between memantine and fatal outcomes in Denmark may be related, in part, to selection of sicker individuals for memantine therapy.

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Cohort Studies; Dementia; Denmark; Donepezil; Female; Heart Failure; Humans; Indans; Male; Medicare; Memantine; Myocardial Infarction; Nootropic Agents; Piperidines; Receptors, N-Methyl-D-Aspartate; United States

To demonstrate the safety and tolerability of galantamine SA in dementia patients transitioned from donepezil.. One group, pretest-posttest. Veterans Affairs (VA) hospital serving U.S. veterans.. Charts of 193 patients changed from donepezil to galantamine SA were reviewed.. In an effort to limit the cost of medications being used for Alzheimer's disease, the Bedford VA Hospital began an initiative to transition patients to the generic sustained-release galantamine SA. A chart review was performed using the VA computerized patient record for all patients transitioned from either donepezil or rivastigmine to galantamine. Progress notes were reviewed for the first three months following initial medication exchange to determine galantamine tolerability and reasons for discontinuation.. Galantamine SA tolerability at three months.. Of the 193 patients transitioned to galantamine SA, 94.3% remained on the drug at three months. The most common reason for medication withdrawal was mental status change (n = 5).. Transition to galantamine SA in a real world clinical setting was well-tolerated among patients with dementia.

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Dementia; Donepezil; Galantamine; Humans; Indans; Middle Aged; Piperidines; Retrospective Studies

Topics: Aged; Brain; Cholinesterase Inhibitors; Cross-Sectional Studies; Dementia; Diagnosis, Differential; Diagnostic Imaging; Donepezil; Early Diagnosis; Evidence-Based Medicine; Humans; Indans; Lewy Body Disease; Mental Disorders; Neuropsychological Tests; Parkinson Disease; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine

Cholinesterase inhibitors (ChEIs) may interact with muscle relaxants given during general anesthesia (GA), increasing the risk of postoperative complications. We evaluated the effects of ChEIs on the postoperative outcomes of older adults who underwent hip fracture surgery.. Population-based cohort study using linked administrative databases.. All individuals with dementia age 66 years or older, who underwent hip fracture surgery between April 1, 2003, and December 31, 2007, in Ontario, Canada.. Use of any ChEI (donepezil, rivastigmine, or galantamine) before surgery.. The primary composite outcome included any of the following: 30-day postoperative mortality; intensive care unit admissions; or in-hospital resuscitation. Secondary outcomes included postoperative respiratory failure and pneumonia.. We stratified the study sample on the basis of residence (community or long-term care [LTC]) and type of anesthetic (general or regional) to create four residence/anesthesia groups. We used propensity scores to match users and nonusers of ChEIs within the residence/anesthesia strata. We then calculated the relative risks (RR) and 95% confidence intervals (CI) for outcomes associated with ChEIs in the matched groups.. A total of 624 pairs of individuals from the community and 725 pairs from LTC were created among individuals who received GA. High rates of postoperative mortality and complications were observed in both ChEI users and nonusers. The RR of the primary outcome associated with ChEI use for individuals receiving GA was 0.88 (95% CI: 0.68-1.16; χ2 = 0.93; df = 1; p = 0.34) and 0.82 (95% CI: 0.63-1.04; χ2 = 2.59; df = 1; p = 0.11) in the community and LTC groups, respectively. In addition, ChEIs were not associated with any significant increased risk of postoperative respiratory complications.. ChEI use was not associated with an increased risk of postoperative complications among older adults with dementia who underwent hip fracture surgery. However, the poor postoperative outcomes overall reinforced the need to prevent fractures and improve outcomes in this population.

Topics: Aged; Aged, 80 and over; Anesthesia, General; Cholinesterase Inhibitors; Cohort Studies; Critical Care; Dementia; Donepezil; Female; Galantamine; Hip Fractures; Humans; Indans; Male; Outcome and Process Assessment, Health Care; Phenylcarbamates; Piperidines; Pneumonia; Postoperative Complications; Respiratory Insufficiency; Resuscitation; Risk; Rivastigmine

Topics: Activities of Daily Living; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Indans; Male; Piperidines

Okadaic acid (OKA) is a potent and selective inhibitor of protein phosphatases, PP2A and PP1. In the present study, we evaluated effect of intracerebroventricular (ICV) bilateral injection of OKA (100 and 200 ng) on memory function and oxidative stress in rats. ICV injection of OKA (200 ng) produced memory impairment as evidenced by no significant decrease in latency time to reach the hidden platform in water maze test. It produced increase in malondialdehyde (MDA), nitrite level, reactive oxygen species (ROS) generation, mitochondrial calcium ion [Ca(2)](i) level and decreased glutathione (GSH) level in rat brain areas, indicating oxidative stress. Furthermore, we evaluated the effect of anti-dementia drugs memantine, a NMDA antagonist, and donepezil, a cholinesterase inhibitor, on OKA ICV induced memory impairment. Administration of memantine (10 mg/kg, p.o.) and donepezil (5 mg/kg, p.o.) for 13 days starting from the OKA injection improved performance in memory tests and also significantly restored GSH, MDA, nitrite levels, ROS generation and [Ca(2+)](i) level. This study demonstrates that the clinically used anti-dementic drugs are effective in OKA induced free radical generation and memory impairment in rats. Thus, OKA ICV induced memory impairment in rat appeared as a useful test model to screen anti-dementia drugs.

Topics: Animals; Brain; Calcium Signaling; Cholinesterase Inhibitors; Dementia; Disease Models, Animal; Donepezil; Drug Evaluation, Preclinical; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Glutathione; Indans; Injections, Intraventricular; Male; Malondialdehyde; Maze Learning; Memantine; Memory; Memory Disorders; Neuropsychological Tests; Nitrites; Okadaic Acid; Oxidative Stress; Piperidines; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Treatment Outcome

Rivastigmine and donepezil are two cholinesterase inhibitors (ChEIs) indicated for the treatment of mild-to-moderate Alzheimer's disease. Dementia-related behavioural issues are typically managed by environmental modification and the use of psychotropics including antipsychotic medications. However, ChEIs have also been associated with reductions in behavioural symptoms in Alzheimer's disease patients. This retrospective, parallel-cohort, hypothesis-generating study investigated whether treatment with rivastigmine is associated with reduced prescription of antipsychotic medications compared with treatment with donepezil.. A combined analysis of two claims databases was conducted. Patients were included if they had a diagnosis of Alzheimer's disease and were newly initiated on either rivastigmine or donepezil. Patients with prior use of memantine and/or antipsychotics were excluded. Kaplan-Meier and Cox analyses were conducted to compare the rate of antipsychotic drug use between the rivastigmine and donepezil groups.. A total of 956 patients receiving rivastigmine and 12 778 patients receiving donepezil formed the study population. Analysis revealed that 64 (6.7%) rivastigmine and 989 (7.7%) donepezil recipients received antipsychotic medications (log-rank test from Kaplan-Meier analysis, p = 0.2289). The Cox regression analysis showed that rivastigmine was associated with a statistically significant reduction in the prescription of antipsychotic drugs relative to donepezil (hazard ratio 0.73; p = 0.044). Older age, longer time between Alzheimer's disease diagnosis and first ChEI dispensing, lower dose of ChEI at treatment initiation and the presence of baseline depression and neuropsychiatric symptoms were associated with a significantly increased likelihood of antipsychotic drug use.. In this retrospective analysis, Alzheimer's disease patients with no prior use of antipsychotics initiated on rivastigmine had a significantly lower rate of prescription of antipsychotic drugs than those treated with donepezil.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Antipsychotic Agents; Cholinesterase Inhibitors; Cohort Studies; Databases, Factual; Dementia; Donepezil; Female; Humans; Indans; Male; Phenylcarbamates; Piperidines; Retrospective Studies; Rivastigmine; Time Factors

(-)-o-Methylvesamicol ((-)-OMV) exhibited in vitro a high affinity for a vesicular acetylcholine transporter (VAChT) (Ki, 6.7 nM), and (-)-o-[(11)C]methylvesamicol [(-)-[(11)C]OMV] exhibited appropriate kinetics and bound mainly to VAChTs in the rat brain. In this study, the in vivo distribution and kinetics of (-)-[(11)C]OMV were evaluated in comparison with [(11)C]SA4503 in disability model monkeys produced by selectively destroying the p75NTR-positive cells in the right hemisphere of the brain using positron emission tomography. Time-activity curves of (-)-[(11)C]OMV showed peaks within 20 min in regions rich in acetylcholine transporters (AchT). (-)-[(11)C]OMV binding in the ipsilateral cortex to the lesion was significantly reduced by 22.0% +/- 6.7% when compared with that in the contralateral region. The decrease (19.3% +/- 2.2%) in (-)-[(11)C]OMV binding in the ipsilateral temporal cortex to the lesion was greater than that (7.4% +/- 4.6%) of [(11)C]SA4503. These results suggested that (-)-[(11)C]OMV may be useful in the study of dementia characterized by degeneration of the cholinergic neurotransmitter system.

Topics: Acetylcholine; Animals; Brain; Carbon Radioisotopes; Dementia; Macaca mulatta; Male; Piperidines; Positron-Emission Tomography; Radiopharmaceuticals; Vesicular Acetylcholine Transport Proteins

Impaired antioxidant defenses are implicated in neurodegenerative disease. The plasma levels of urate, a water-soluble antioxidant, are reduced in Alzheimer's disease (AD).. We aimed to test the hypotheses that high plasma urate at baseline is associated with: (1) a reduced rate of conversion from mild cognitive impairment (MCI) to AD and (2) a lower rate of cognitive decline in MCI.. Plasma urate was obtained at baseline from 747 participants in a 3-year, randomized, double-blind, placebo-controlled study of donepezil, vitamin E or placebo for delaying the progression of MCI to AD.The association between baseline urate and conversion from MCI to AD was examined by Cox proportional hazards regression. The relationship between baseline urate and cognitive change on the cognitive subscale of the Alzheimer's Disease Assessment Scale was evaluated by longitudinal analysis.. Baseline plasma urate was not associated with the rate of conversion of MCI to AD. In the placebo arm, high plasma urate was related to a slower rate of cognitive decline over 3 years, although this was not reproduced in the other treatment arms.. While plasma urate levels did not predict the progression of MCI to AD, high urate may be associated with a reduced rate of cognitive decline in MCI patients not treated with donepezil or vitamin E. The results support the investigation of biomarkers of antioxidant status as risk factors for cognitive decline in MCI.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Boston; Cognition Disorders; Confounding Factors, Epidemiologic; Dementia; Disease Progression; Donepezil; Female; Humans; Incidence; Indans; Male; Middle Aged; Nootropic Agents; Piperidines; Prevalence; Survival Analysis; Uric Acid; Vitamin E

The present study was undertaken to clarify the effects of anti-dementia drugs on sleep pattern in rats. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscle of rats for the electroencephalogram (EEG) and electromyogram (EMG), respectively. EEG and EMG were recorded with an electroencephalograph. SleepSigh ver. 2.0 was used for analysis of the sleep-wake state. Total times of waking, non-rapid eye movement (non-REM) sleep, and rapid eye movement (REM) sleep were measured from 10:30 to 16:30. Galantamine had no significant influence on the sleep pattern. On the other hand, donepezil and memantine showed significant increases in sleep latency and total waking time and a decrease in total non-REM sleep time. Furthermore, memantine decreased total REM sleep time. To investigate the characteristics of non-REM sleep in detail, non-REM sleep was classified as stage 1, 2, or 3 according to the depth of sleep. Different from donepezil and galantamine, memantine significantly decreased stage 1 and increased stage 3 in non-REM sleep. From these findings, it can be concluded that galantamine caused no sleep disturbance, different from donepezil and memantine.

Topics: Animals; Dementia; Donepezil; Dose-Response Relationship, Drug; Electroencephalography; Electromyography; Excitatory Amino Acid Antagonists; Galantamine; Indans; Male; Memantine; Nootropic Agents; Piperidines; Rats; Rats, Wistar; Sleep; Sleep Wake Disorders; Sleep, REM

Cognitive dysfunction is a characteristic of various forms of dementia such as Alzheimer's disease (AD) and a core feature of schizophrenia. As part of our continuing efforts to develop agents for cognitive enhancement, we have been focused on the 5-HT(6) receptor-one of the emerging therapeutic targets in this area. Herein, we report the identification of a novel series of 3-piperidinyl-5-sulfonylindazole derivatives as potent 5-HT(6) antagonists. The synthesis and SAR of this class of compounds are reported.

Topics: Cognition Disorders; Dementia; Humans; Indazoles; Ligands; Piperidines; Receptors, Serotonin; Serotonin Antagonists; Sulfinic Acids

To determine if choice of drug and ease of administration affect persistence of therapy with cholinesterase inhibitors (ChEIs) for treatment of dementia.. An observational administrative health database study was conducted in 5622 patients aged >or=65 years who received a new prescription for donepezil (DON), rivastigmine (RIV) or galantamine (GAL) from February to May 2006. Patients were followed for 1 year from initiation of therapy to determine percentage persistence and days of therapy. Once-daily galantamine extended release (GAL-ER) was compared with twice-daily galantamine immediate release (GAL-IR) to determine if ease of administration affected persistence. Previous treatment with ChEIs was also documented.. One-year persistence rates were significantly different among the ChEIs: GAL-ER 54% (95% CI 51, 57), DON 46% (95% CI 43, 49) and RIV 40% (95% CI 37, 43). Average days of therapy were greater for GAL-ER (293) than for RIV (272), but there were no differences between DON (287) and GAL-ER or DON and RIV. One-year persistence was significantly greater for GAL-ER 54% (95% CI 48, 59) than for GAL-IR 44% (95% CI 39, 50), although there was no significant difference in days of therapy (293 vs 286, respectively). More patients currently treated with RIV (40.5%) or GAL-ER (32.3%) had received previous treatment with a different ChEI than with DON (21.9%).. Among possible factors affecting persistence of ChEI therapy for dementia, choice of drug, ease of administration and previous treatment appear to be important.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Databases, Factual; Delayed-Action Preparations; Dementia; Donepezil; Follow-Up Studies; Galantamine; Humans; Indans; Medication Adherence; Phenylcarbamates; Piperidines; Rivastigmine

Cholinesterase inhibitors and N-methyl-D-aspartic acid (NMDA) receptor antagonists are Food and Drug Administration (FDA) approved for the treatment of moderate to severe Alzheimer's disease. As dementia progresses to the end stage and patients become hospice-eligible, clinicians consider whether or not to continue these therapies without the benefit of scientific evidence. We sought to describe hospice medical directors practice patterns and experiences in the use and discontinuation of cholinesterase inhibitors and NMDA receptor antagonists in hospice patients that meet the Medicare hospice criteria for dementia.. Mail survey of hospice medical directors from a random sample from the National Hospice and Palliative Care Organization.. Of the 413 eligible participants, 152 completed surveys were returned, yielding a response rate of 37%. Of the respondents, 75% and 33% reported that at least 20% of their patients were taking a cholinesterase inhibitor or memantine, respectively, at the time of hospice admission. The majority of respondents do not consider these therapies effective in persons with end-stage dementia, however, a subset believe that these medications improved patient outcomes including stabilization of cognition (22%), decrease in challenging behaviors (28%), and maintenance of patient function (22%) as well as caregiver outcomes namely reduced caregiver burden (20%) and improved caregiver quality of life (20%). While 80% of respondents recommended discontinuing these therapies to families at the time of hospice enrollment, 72% of respondents reported that families experienced difficulty stopping these therapies. A subset of respondents observed accelerated cognitive (30%) and functional decline (26%) or emergence of challenging behaviors (32%) with medication discontinuation.. The findings from this survey indicate that cholinesterase inhibitors and/or NMDA receptor antagonists are prescribed for a subset of patients with advanced dementia and that a proportion of hospice medical directors report clinical benefit from the ongoing use of these agents. In addition, physician preferences for discontinuing these therapies are frequently at odds with the wishes of family members. Prospective studies are needed to evaluate the clinical impact of the discontinuation of these therapies on patient and caregiver outcomes.

Topics: Age Factors; Aged; Aged, 80 and over; Antiparkinson Agents; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Health Care Surveys; Health Status Indicators; Hospice Care; Humans; Indans; Male; Memantine; Palliative Care; Physician Executives; Piperidines; Receptors, N-Methyl-D-Aspartate

Topics: Aged; Aged, 80 and over; Benzilates; Chi-Square Distribution; Cholinergic Antagonists; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Therapy, Combination; Female; Humans; Indans; Male; Middle Aged; Piperidines; Prospective Studies; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive

In the present study, role of brain insulin receptors (IRs) in memory functions and its correlation with acetylcholinesterase (AChE) activity and oxidative stress in different brain regions were investigated in intracerebroventricular (ICV) streptozotocin (STZ) induced dementia model. Rats were treated with STZ (3 mg/kg, ICV) on day 1 and 3. Donepezil (5 mg/kg po) and melatonin (20 mg/kg ip) were administered in pre- and post-treatment schedules. Morris water maze test was done on day 14 and animals were sacrificed on day 21 from 1st STZ injection. Memory deficit was found in STZ group as indicated by no significant decrease in latency time antagonized by donepezil and melatonin. IR protein level was found significantly increased in trained group as compared to control, whereas STZ decreased IR level significantly as compared to trained rats in hippocampus which indicates that IR is associated with memory functions. STZ induced decrease in IR was reversed by melatonin but not by donepezil. Melatonin per se did not show any significant change in IR level as compared to control. AChE activity (DS and SS fraction) was found to be increased in hippocampus in STZ group as compared to trained which was inhibited by donepezil and melatonin. Increase in MDA level and decrease in GSH level were obtained in STZ group indicating oxidative stress, which was attenuated by donepezil and melatonin. Effectiveness of antioxidant, melatonin but not of anti-cholinesterase, donepezil against STZ induced changes in IR indicates that IR is more affected with oxidative stress than cholinergic changes.

Topics: Acetylcholinesterase; Animals; Antibiotics, Antineoplastic; Biomarkers; Blood Glucose; Blotting, Western; Body Weight; Brain Chemistry; Cholinesterase Inhibitors; Dementia; Donepezil; Electrophoresis, Polyacrylamide Gel; Glutathione; Indans; Injections, Intraventricular; Male; Malondialdehyde; Maze Learning; Oxidative Stress; Piperidines; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Streptozocin

Topics: Aged; Aspartic Acid; Brain; Cognition Disorders; Dementia; Donepezil; Female; Humans; Indans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neuroprotective Agents; Neuropsychological Tests; Phenylcarbamates; Piperidines; Psychiatric Status Rating Scales; Rivastigmine; Treatment Outcome

To quantify the association between cholinesterase inhibitors (ChE-Is) and a new diagnosis of bradycardia and to evaluate the clinical significance of bradycardia.. Cox proportional hazards with time-dependent exposures were used to evaluate the association and examine the dose effect for donepezil and bradycardia.. New England Veterans Affairs Healthcare System.. Patients with dementia who received care between January 1999 and June 2007 (N=11,328).. Bradycardia was defined using three methods using a combination of International Classification of Diseases, Ninth Revision, codes and recorded heart rates of less than 60 beats per minute.. A greater risk for bradycardia was found in patients taking any ChE-Is than in the no-treatment group (adjusted hazard ratio (HR)=1.4, 95% confidence interval (CI)=1.1-1.6). A dose-response effect was observed for donepezil, with the highest-dose group at greatest risk (HR=2.1, 95% CI=1.5-2.9). Results were consistent regardless of bradycardia definition. Patients with bradycardia were more likely to fall, experience syncope, or need a pacemaker implantation than those without.. Using a large cohort, a modestly greater risk of bradycardia was found in patients with dementia taking ChE-Is than in those not taking these drugs. In patients taking donepezil, the risk of bradycardia may increase with increasing doses. Because of the potential clinical consequences, monitoring for bradycardia may be warranted in patients with dementia treated with ChE-Is.

Topics: Alzheimer Disease; Bradycardia; Cholinesterase Inhibitors; Cross-Sectional Studies; Dementia; Donepezil; Dose-Response Relationship, Drug; Drug Therapy, Combination; Galantamine; Heart Rate; Hospitals, Veterans; Humans; Incidence; Indans; Massachusetts; Nootropic Agents; Phenylcarbamates; Piperidines; Risk; Rivastigmine; Veterans

Topics: Aged, 80 and over; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Therapy, Combination; Galantamine; Humans; Indans; Male; Piperidines

The present study was undertaken to investigate the characteristics of morphine in rat sleep patterns and also the effects of donepezil and memantine on somnolence caused by morphine. Electrodes were chronically implanted into the cortex and dorsal neck muscle of rats for electroencephalogram (EEG) and electromyogram (EMG) recordings, respectively. EEG and EMG were recorded with an electroencephalograph. SleepSigh ver.2.0 was used to analyse the sleep-wake state. Total times of wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep were measured from 10:00 to 16:00. Morphine at a high dose caused a significant decrease in sleep latency and total REM sleep time, although the drug at low doses caused significant increases in sleep latency and total awake time, and a significant decrease in NREM sleep time. Donepezil, memantine and methylphenidate antagonized the decrease in sleep latency caused by morphine. From these findings, it can be concluded that morphine caused somnolence, and donepezil and memantine are useful for somnolence caused by morphine, similar to methylphenidate.

Topics: Animals; Dementia; Donepezil; Electroencephalography; Electromyography; Indans; Male; Memantine; Methylphenidate; Morphine; Piperidines; Rats; Rats, Wistar; Sleep Stages

Topics: Cognition Disorders; Dementia; Depression; Donepezil; Humans; Indans; Nootropic Agents; Piperidines

To evaluate the prevalence of cholinesterase inhibitor (ChI) treatment in subjects with dementia in European countries.. We studied the prevalence of treatment in subjects with dementia among European countries in 2004 (Belgium, France, Germany, Italy, the Netherlands, Poland, Portugal, Spain and the United Kingdom) by using estimates of prevalence of dementia and of ChI treatments according to sales and reimbursement data.. In 2004, estimated prevalence of ChI use among subjects with dementia ranged from 3.0% in the Netherlands to 20.3% in France. It was 17.5% in Spain, 6.7% in the UK and 5.9% in Italy. Donepezil was used by more than 60% of patients using a single ChI and represented almost 50% of reimbursements for patients that had used at least two different ChIs during the year. Galantamine and rivastigmine were respectively used by 22 and 18% of subjects using a single drug and 27 and 23% of reimbursements for patients that had used at least two different ChIs. Nevertheless, different patterns of use were found for individual countries.. Prevalence of treatment by ChIs among subjects with dementia remains weak and varies greatly across Europe. Differences in reimbursement rates and health policies could partly explain these variations, as ChIs could have failed to convince health authorities because the outcomes considered for trials are not used by clinicians in their everyday practice. If donepezil was highly predominant across countries, variations in rivastigmine and galantamine importance could reflect local market specificities.

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Europe; Galantamine; Health Policy; Humans; Indans; Insurance, Health, Reimbursement; Phenylcarbamates; Piperidines; Practice Patterns, Physicians'; Prevalence; Rivastigmine

It has been reported that the cholinesterase inhibitor, donepezil, improves cognitive decline in patients with Parkinson's disease dementia (PDD). However, this improvement was dominant for frontal lobe dysfunction, and the increase in the Mini-Mental State Examination (MMSE) score was minimal. We report a PDD patient with a decline of regional cerebral blood flow (rCBF) in the posterior cingulate cortex, precunei, and bilateral parietotemporal association cortex, as determined by single-photon emission computed tomography (SPECT) using the easy Z-scores imaging system (e-ZIS). Upon administration of donepezil, both the rCBF and MMSE score increased. The effectiveness of donepezil may vary based on the rCBF pattern in PDD.

Topics: Aged; Cerebrovascular Circulation; Dementia; Donepezil; Gyrus Cinguli; Humans; Indans; Male; Mental Status Schedule; Neuropsychological Tests; Nootropic Agents; Parkinson Disease; Piperidines; Regional Blood Flow; Treatment Outcome

Topics: Adult; Aged; Aged, 80 and over; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Utilization Review; Galantamine; Humans; Indans; Middle Aged; Phenylcarbamates; Piperidines; Quebec; Rivastigmine

To describe patterns of Acetylcholinesterase inhibitor (ACI) use in an Assisted Living (AL) population, and the association of ACIs with retention in AL.. As part of the Maryland Assisted Living Study (MD-AL), 198 residents of 22 ALs were evaluated. Dementia was diagnosed in 134, and specifically Alzheimer's disease (AD) in 79, by an expert consensus panel. Data was collected on ACI agent and dose. Vital status and location were recorded every 6 months. Other data included age, duration of residence, general medical health rating (GHMR), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia (CSDD) and number of non-psychiatric medications.. The overall ACI treatment rate was 31%. 34.5% of participants with mild to moderate AD were taking ACIs. Only two in seven participants taking rivastigmine were taking an adequate dose. Participants with AD on ACI's did not differ significantly from those not on ACI's in any of the secondary measures except age and duration of residence, those on the agents being somewhat younger and more recently admitted. For participants with AD, only ACI use was significantly associated with retention in AL at 6 months, with a relative risk of death or discharge to higher level care of 0.217. Baseline MMSE was associated with retention for those with non-AD dementia. In a survival analysis ACI use was associated with 228.75 days longer retention in participants with AD.. ACIs have low rates of use in AL and are associated with better retention for residents with AD.

Topics: Activities of Daily Living; Aged, 80 and over; Alzheimer Disease; Assisted Living Facilities; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Administration Schedule; Female; Galantamine; Health Surveys; Homes for the Aged; Humans; Indans; Male; Mental Status Schedule; Neuropsychological Tests; Phenylcarbamates; Piperidines; Retention, Psychology; Rivastigmine; Survival Analysis; Treatment Outcome

The treatment of rapidly deteriorating dementia is always very challenging. This case report describes a 78-year-old male patient with rapidly developing dementia treated successfully with orally disintegrating olanzapine, memantine, donepezil, omega-3 and vitamin-B complex. The prevailing fatalism and treatment nihilism regarding treatment of dementia should give way to more hope and optimism. Several important treatment dillemas in rapidly developing dementia are discussed.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cholinesterase Inhibitors; Dementia; Depression; Disease Progression; Donepezil; Dopamine Agonists; Drug Therapy, Combination; Electrocardiography; Electroencephalography; Humans; Indans; Male; Memantine; Neuropsychological Tests; Olanzapine; Piperidines; Severity of Illness Index

The most commonly used model of Down syndrome, the Ts65Dn (TS) mouse, is trisomic for most of the region of MMU16 that is homologous to HSA21. This mouse shares many phenotypic characteristics with people with Down syndrome including behavioral and cognitive alterations. The objective of this study was to analyze the ability of two drugs that improve cognition in different experimental models, the acetylcholinesterase inhibitor donepezil and the non-competitive GABA(A) antagonist pentylenetetrazole (PTZ), to improve the cognitive deficits found in TS mice. The drugs were administered p.o. to TS and CO mice for 8 weeks and a behavioral characterization was performed. Sensorimotor abilities, including vision, hearing, strength and motor coordination, as well as locomotor activity in the home cage, were not modified by any chronic treatment in TS and CO mice. TS mice showed altered equilibrium in the aluminium rod, and this effect was larger under PTZ treatment. This result may indicate a potential adverse effect of PTZ in Ts65Dn mice. Learning and memory were evaluated in TS and CO mice after both treatments in the Morris water maze. Donepezil administration did not modify learning and memory in animals of any genotype. On the other hand, PTZ administration rescued TS performance in the Morris water maze.

Topics: Acetylcholine; Animals; Brain; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Disease Models, Animal; Donepezil; Down Syndrome; Drug Administration Schedule; GABA Antagonists; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Indans; Male; Maze Learning; Memory Disorders; Mice; Mice, Neurologic Mutants; Neural Inhibition; Pentylenetetrazole; Piperidines; Receptors, GABA-A; Treatment Outcome; Trisomy

Oxidative stress is a major factor implicated in the degeneration of cholinergic neurons in Alzheimer's disease. Presently, cholinesterase inhibitors are the mainstay of therapy for Alzheimer's disease. However, the potential of cholinesterase inhibitors as antioxidants, an important aspect for neuroprotection, has not been properly investigated. Therefore, the present study was designed to investigate the influence of antidementia drugs, tacrine and donepezil, on biochemical markers of oxidative stress, glutathione (GSH) and malondialdehyde (MDA), and acetylcholinesterase activity in the brain in a streptozotocin-induced experimental model of dementia in mice. Intracerebral (i.c.) injection of streptozotocin at a dose of 0.5 mg/kg on 1st and 3rd days caused significant deficits in memory function, as evaluated in a passive avoidance test and Morris Water Maze (spatial memory) test 14 days after the 1st dose. Mice were treated with tacrine and donepezil at a dose of 5 mg/kg orally in separate groups. Both tacrine- and donepezil-treated mice showed a significant improvement of the streptozotocin (i.c.)-induced memory impairment. Streptozotocin (i.c.) administration caused a significant decrease in GSH and increase in MDA as compared to control, indicating a state of oxidative stress in the brain of streptozotocin (i.c.) amnesic mice. Treatment of streptozotocin (i.c.) amnesic mice with tacrine or donepezil did not cause significant changes in GSH and MDA levels in the brain as compared to control. Streptozotocin amnesic mice had raised acetylcholinesterase activity in the brain while there was a significant decrease in brain acetylcholinesterase activity in tacrine- and donepezil-treated streptozotocin (i.c.) mice. Thus, results indicate that tacrine and donepezil, beside inhibition of acetylcholinesterase, may also suppress oxidative stress.

Topics: Acetylcholinesterase; Animals; Avoidance Learning; Brain; Dementia; Disease Models, Animal; Donepezil; Glutathione; Indans; Male; Malondialdehyde; Maze Learning; Memory Disorders; Mice; Nootropic Agents; Oxidative Stress; Piperidines; Streptozocin; Tacrine

Topics: Activities of Daily Living; Affect; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Excitatory Amino Acid Antagonists; Galantamine; Humans; Indans; Memantine; Phenylcarbamates; Piperidines; Quality of Life; Rivastigmine; Tacrine

The American College of Physicians and American Academy of Family Physicians developed this guideline to present the available evidence on current pharmacologic treatment of dementia.. The targeted literature search included evidence related to the effectiveness of 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementia for outcomes in the domains of cognition, global function, behavior/mood, and quality of life/activities of daily living. RECOMMENDATION 1: Clinicians should base the decision to initiate a trial of therapy with a cholinesterase inhibitor or memantine on individualized assessment. (Grade: weak recommendation, moderate-quality evidence.) RECOMMENDATION 2: Clinicians should base the choice of pharmacologic agents on tolerability, adverse effect profile, ease of use, and cost of medication. The evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia. (Grade: weak recommendation, low-quality evidence.) RECOMMENDATION 3: There is an urgent need for further research on the clinical effectiveness of pharmacologic management of dementia.

Topics: Activities of Daily Living; Affect; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Excitatory Amino Acid Antagonists; Galantamine; Humans; Indans; Memantine; Phenylcarbamates; Piperidines; Quality of Life; Rivastigmine; Tacrine

The present study was undertaken to investigate the beneficial effect of HIV protease inhibitor Indinavir on memory deficits associated with experimental dementia of Alzheimer disease's (AD) type. Dementia was induced in Swiss albino mice by administration of Celecoxib (100 mg kg(-1) orally, daily for 9 days) or Streptozotocin (3 mg kg(-1) administered intracerebroventricularly on 1st and 3rd day) and the cognitive behaviors of Swiss albino mice were assessed using Morris water maze test. Brain acetyl cholinesterase (AChE) activity was measured by Ell Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively to assess total oxidative stress. Donepezil (0.1 mg kg(-1) i.p.) served as positive control in the present investigation. Celecoxib as well as Streptozotocin (STZ) produced a significant loss of learning and memory. Indinavir (100 and 200 mg kg(-1) orally) successfully attenuated Celecoxib as well as STZ induced cognitive deficits. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in Celecoxib as well as STZ treated animals, which were significantly attenuated by Donepezil and Indinavir. Study highlights the potential of Indinavir in memory dysfunctions associated with dementia of AD.

Topics: Acetylcholinesterase; Animals; Antibiotics, Antineoplastic; Brain; Celecoxib; Cyclooxygenase Inhibitors; Dementia; Donepezil; Female; Glutathione; HIV Protease Inhibitors; Indans; Indinavir; Male; Maze Learning; Memory; Memory Disorders; Mice; Nootropic Agents; Oxidative Stress; Piperidines; Pyrazoles; Streptozocin; Sulfonamides; Thiobarbituric Acid Reactive Substances

Topics: Antiparkinson Agents; Cholinesterase Inhibitors; Dementia; Disease Progression; Donepezil; Galantamine; Humans; Indans; Memantine; Neuroprotective Agents; Nootropic Agents; Palliative Care; Phenylcarbamates; Piperidines; Prognosis; Receptors, N-Methyl-D-Aspartate; Rivastigmine

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Galantamine; Guidelines as Topic; Humans; Indans; Memantine; Phenylcarbamates; Piperidines; Rivastigmine; Tacrine

Topics: Aged; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Catatonia; Chlorpromazine; Cholinesterase Inhibitors; Cognition Disorders; Creatine Kinase; Dementia; Disease Progression; Donepezil; Female; Humans; Indans; Lorazepam; Muscle Rigidity; Neuroleptic Malignant Syndrome; Olanzapine; Piperidines; Recurrence; Risperidone

Dementia with Lewy Body and Alzheimer's disease exhibit degeneration of the cholinergic neurons, and currently, the primary target of treatment is the cholinergic neurotransmitter system. [(123)I]-IBVM is a highly selective radioligand for in vivo visualization of the vesicular acetylcholine transporter (VAChT) using single photon emission computed tomography. This study compares different noninvasive methods using the occipital cortex as a reference region for the quantification of [(123)I]-IBVM binding in six older, healthy volunteers: two kinetic analyses based on one-tissue (1TCM) or two-tissue compartment model (2TCM), one linear and one multilinear analysis, and a simplified peak equilibrium analysis. Time-activity curves were well described by a 1TCM for all regions. The 2TCM converged reliably only in the striatum. Goodness of fit was not improved by using a 2TCM as compared with a 1TCM. The multilinear analysis gave binding potentials similar to the 1TCM while being more robust. The peak equilibrium method might prove to be a useful simplified analysis. The binding potentials obtained with reference region methods strongly correlated with results from invasive blood-sampling analysis. Noninvasive quantification of [(123)I]-IBVM data provides reliable estimates of VAChT binding, which is most valuable to study neurodegenerative diseases with specific cholinergic alteration.

Topics: Aged; Brain; Dementia; Humans; Iodine Radioisotopes; Kinetics; Models, Biological; Piperidines; Radiopharmaceuticals; Tetrahydronaphthalenes; Tomography, Emission-Computed, Single-Photon; Vesicular Acetylcholine Transport Proteins

Inflammation has been recently implicated in pathogenesis of dementia disorders. Effect of anti-dementia (Acetylcholinesterase inhibitor) drugs tacrine, rivastigmine and donepezil were studied on neuroinflammation induced by intraperitoneal administration of lipopolysaccharide (LPS) in mice. Interleukin-2 (IL-2) and isoforms of acetylcholinesterase (AChE) were estimated in different brain areas as marker for neuroinflammation and cholinergic activity respectively. LPS significantly increased the level of IL-2 in all the brain areas while enhancement of AChE activity varied in brain areas. It was found that administration of tacrine, rivastigmine and donepezil in mice significantly attenuated the LPS induced increased levels of IL-2 along with the significant reduction of AChE activity predominantly in salt soluble (SS) fraction as compared to the detergent soluble (DS) fraction in a dose dependent manner. In vitro effect of LPS was also studied in different brain areas. LPS significantly increased the AChE activity in SS fractions but the significant increase was not found in DS fractions. The present study indicate that cholinesterase inhibitor anti-dementia drugs are effective against LPS induced neuroinflammation that may be linked to enhanced cholinergic activity.

Topics: Acetylcholinesterase; Analysis of Variance; Animals; Brain; Cholinesterase Inhibitors; Dementia; Donepezil; Dose-Response Relationship, Drug; Indans; Inflammation; Injections, Intraperitoneal; Interleukin-2; Lipopolysaccharides; Mice; Phenylcarbamates; Piperidines; Rivastigmine; Tacrine

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Double-Blind Method; Ginkgo biloba; Humans; Indans; Piperidines; Randomized Controlled Trials as Topic

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Double-Blind Method; Ginkgo biloba; Humans; Indans; Piperidines; Randomized Controlled Trials as Topic

Topics: Aged; Dementia; Donepezil; Female; Humans; Indans; Long QT Syndrome; Nootropic Agents; Piperidines; Tachycardia, Ventricular

(1) Three cholinesterase inhibitors are marketed in France for the treatment of Alzheimer's disease: donepezil, galantamine and rivastigmine. Tremor and dystonia are known adverse effects of cholinesterase inhibitors. (2) In patients with Parkinson's disease who have cognitive disorders, or in patients with Lewy body dementia, exacerbations of parkinsonism and tremor have been observed during treatment with cholinesterase inhibitors at normal doses. The disorders were reversible on withdrawal of the cholinesterase inhibitor. (3) Withdrawal of cholinesterase inhibitors should be considered if gait disorders, falls or parkinsonism occur or worsen during treatment.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Dystonia; France; Galantamine; Humans; Indans; Lewy Body Disease; Parkinson Disease; Phenylcarbamates; Piperidines; Tremor

Topics: Dementia; Donepezil; Humans; Indans; Nootropic Agents; Piperidines; Prejudice; Randomized Controlled Trials as Topic

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Dopamine Agents; European Union; Galantamine; Humans; Indans; Memantine; Neurotransmitter Agents; Phenylcarbamates; Piperidines; Reimbursement Mechanisms; Rivastigmine

The authors present a case of a patient with dementia with mood symptoms and multiple neurological manifestations of fragile X-associated tremor/ataxia syndrome (FXTAS). Despite a gradually deteriorating neurological course, he was managed for 2 years with combination therapy of donepezil and venlafaxine, which resulted in improvement and relative stabilization of his psychiatric status. Psychiatrists are hereby alerted to the description of a novel dementia syndrome that may respond to pharmacological intervention commonly used for other dementias.

Topics: Aged; Antidepressive Agents, Second-Generation; Ataxia; Atrophy; Brain; Cyclohexanols; Dementia; Dominance, Cerebral; Donepezil; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fragile X Mental Retardation Protein; Fragile X Syndrome; Genetic Carrier Screening; Humans; Image Processing, Computer-Assisted; Indans; Magnetic Resonance Imaging; Male; Mental Status Schedule; Mood Disorders; Neurologic Examination; Neuropsychological Tests; Nootropic Agents; Piperidines; Tremor; Trinucleotide Repeats; Venlafaxine Hydrochloride

Topics: Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Indans; Intestinal Pseudo-Obstruction; Male; Piperidines; Withholding Treatment

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Indans; Piperidines; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome

To report 2 cases of patients with Down syndrome and severe cognitive impairment who gained dramatic improvements in quality of life (QOL) upon donepezil treatment.. Case 1. A 38-year-old woman with Down syndrome, diagnosed with secondary progressive dementia when her mental state had deteriorated rapidly after graduation from junior high school, started donepezil treatment. The loading dose was 3 mg/day and was increased to 5 mg/day for maintenance. One month after the dose was increased, adverse effects such as soft stool and urinary incontinence appeared. These adverse effects disappeared when the dose was decreased again to 3 mg/day. Her QOL improved dramatically with this minimal dose. She recovered verbal and written communication skills that she had lost for the past 21 years. Case 2. A 22-year-old man with Down syndrome, who had been diagnosed as having severe mental retardation, was put on donepezil therapy. Both loading and maintenance doses were 3 mg/day. His QOL had also dramatically improved, with some recovery in verbal communication. Transient agitation/violence and transient muscle weakness appeared during the first few months of treatment.. Patients with Down syndrome may be more sensitive to donepezil therapy than others and may benefit from this medicine, although they may also have adverse effects more frequently.. Donepezil may be a useful medicine for some patients with Down syndrome with severe cognitive impairment or mental retardation if the adverse effects are manageable.

Topics: Adult; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Down Syndrome; Female; Humans; Indans; Intellectual Disability; Male; Piperidines; Quality of Life

Sixteen patients with Alzheimer's disease (AD) and 15 patients with vascular dementia (VaD) associated with subcortical white matter lesions or subcortical cardiovascular accidents (CVAs) were treated with donepezil for 16 weeks. Within-group analyses for the AD group revealed significant improvement on some tests of working memory, and marginal improvement on the Mini-Mental State Examination and on tests of immediate free recall from a serial list-learning task. Identical analyses for the VaD group revealed substantial gains on tests of working memory and delayed recognition memory. These data suggest that medication such as donepezil may act to improve the working memory deficits known to be associated with dementia patients with subcortical vascular lesions. The clinical implications of these findings are discussed.

Topics: Aged; Alzheimer Disease; Blood Vessels; Brain; Dementia; Dementia, Vascular; Donepezil; Female; Humans; Indans; Male; Memory; Memory, Short-Term; Mental Recall; Neuropsychological Tests; Nootropic Agents; Piperidines; Psychiatric Status Rating Scales; Stroke

Topics: Cholinesterase Inhibitors; Comorbidity; Cross-Over Studies; Cross-Sectional Studies; Dementia; Donepezil; Double-Blind Method; Humans; Indans; Mental Status Schedule; Neuropsychological Tests; Outcome Assessment, Health Care; Parkinson Disease; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine

Topics: Cholinesterase Inhibitors; Clinical Trials as Topic; Dementia; France; Galantamine; Humans; Indans; Mortality; Piperidines; Treatment Outcome

Since cholinesterase inhibitors (CEIs) were approved for use in mild to moderate Alzheimer's disease, the therapeutic efficacy of this class of medications has largely centered on demonstration of short-term improvement in cognition and global function. Later evidence suggested that the beneficial effects of CEIs might be sustainable for at least 3 years and that CEIs may have a disease-modifying effect on Alzheimer's disease. These broad-ranging, long-term effects may explain the recent finding that the use of a CEI among nursing home residents with dementia was associated with lower mortality.. The goal of this study was to investigate whether donepezil treatment is associated with reduced mortality in nursing home residents who have dementia.. We performed a retrospective matched cohort study using the Systematic Assessment of Geriatric Drug Use via Epidemiology database, which contains data collected with the Minimum Data Set on a cross section of 915,469 nursing home residents aged > 65 years between 1998 and 2000 in 6 US states. We identified users of donepezil (5 and 10 mg) and an equal number of matched nonusers in the same facility, date of donepezil use, level of cognitive function, and dementia diagnosis. Comparisons of the 2 groups were made for sociodemographic variables, dementia severity, number of medications, and major comorbid illnesses (heart disease, cancer, diabetes mellitus, chronic obstructive pulmonary disease, and malnutrition), as well as survival over the 2-year study period.. A total of 5423 users and 5423 nonusers of donepezil were identified. Based on Cox proportional hazards models, donepezil users showed a lower mortality rate than nonusers. The hazard rate ratio was 0.89 (95% CI, 0.83-0.95). After adjusting for the confounding variables, sociodemographic factors, other psychotropic drugs, and comorbid conditions, this survival advantage remained (hazard rate ratio, 0.90; 95% CI, 0.84-0.96).. A relationship was observed between treatment of nursing home residents with donepezil and lower mortality. If the relationship was due to a direct effect of donepezil use, then this observation has implications for the socioeconomic impact of CEI therapy in those with advanced dementia in the nursing home. These implications deserve future investigation.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cohort Studies; Cross-Sectional Studies; Databases, Factual; Dementia; Donepezil; Female; Humans; Indans; Male; Nootropic Agents; Nursing Homes; Piperidines; Proportional Hazards Models; Retrospective Studies; Tacrine

Topics: Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Humans; Indans; Piperidines; Treatment Failure; United Kingdom

Clinical studies have shown efficacy of cholinesterase inhibitors (eg, donepezil) in mild to moderate Alzheimer's disease (AD). However, there are limited studies examining the impact on health care costs of cholinesterase inhibitors prescribed in routine clinical practice.. The purpose of this study was to estimate the impact of donepezil use on health care costs and utilization in patients with mild to moderate AD and related dementias.. This case-control study was conducted using data from the Health Insurance Plan of Greater New York (New York, New York). Data from patients with predominantly mild to moderate AD and related dementias who were enrolled in this Medicare managed care plan from January 1, 1999, to December 31, 2002, were included. The health care costs and utilization of patients who had received donepezil prescribed in routine clinical practice were compared with those of patients who had never received donepezil or other cholinesterase inhibitors (control group). The 2 study groups were matched for age, sex, number of comorbid conditions, and presence of complications of late-stage dementia. Regression analysis was used to estimate the impact of donepezil use on health care costs and utilization during a 12-month follow-up period, controlling for characteristics associated with the outcomes. The analyses did not use a direct measure of disease severity but instead used proxy measures of severity based on medical conditions associated with late-stage dementia.. Data from 687 patients were included in the study. The donepezil group comprised 229 patients (140 women, 89 men; mean age, 79.6 years); the control group, 458 patients (280 women, 178 men; mean age, 80.0 years). The mean costs of medical services per year in the donepezil group were US $2500 (95% CI, $300-$4671) less than those in the control group (P = 0.024). Lower medical costs in the donepezil group ($3325; 95% CI, $1163-$5486; P < 0.003 vs controls) were largely attributable to the lower costs of services performed in the hospital ($2594; 95% CI, $846-$4341; P < 0.004 vs controls) and postacute skilled nursing facility (SNF) ($1012; 95% CI, $444-$1579; P < 0.001 vs controls), which were partially offset by $1241 in higher prescription, physician's office, and outpatient hospital costs. Patients receiving donepezil had shorter mean lengths of stay in the hospital (3.00 vs 5.43 days; 95% CI, 0.66-4.19; P < 0.008) and postacute SNF (0.42 vs 3.40 days; 95% CI, 1.28-4.69; P < 0.001) but a higher mean number of physician's office visits (10.91 vs 7.91 visits; 95% CI, 1.63-4.36; P < 0.001) compared with controls.. In this case-control study in patients with predominantly mild to moderate AD and related dementias, donepezil therapy prescribed in routine clinical practice was associated with reduced health care costs to the Medicare managed care plan studied. The findings support previous pharmacoeconomic studies with larger sample sizes obtained over a longer period of time, and with improved case-matching criteria.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Case-Control Studies; Cholinesterase Inhibitors; Dementia; Disease Progression; Donepezil; Drug Utilization; Female; Health Care Costs; Humans; Indans; Male; Managed Care Programs; Medicare; Piperidines

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) overlap in phenomenology and neurochemical deficits. We hypothesised they would not differ in their response to the cholinesterase inhibitor donepezil.. We recruited 70 subjects, 30 DLB and 40 PDD, in an open label study to compare the efficacy of donepezil in these two patient groups. They were assessed at baseline, 4, 12 and 20 weeks. The main outcome measures were the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and motor sub-section of the Unified Parkinson's Disease Rating Scale (UPDRS III).. PDD patients were younger than DLB and had more severe parkinsonism at baseline. The groups were similar on all other variables of interest. By 20 weeks the mean MMSE score increased by 3.9 points in the DLB group and by 3.2 points in PDD. The mean NPI score reduced by 14.6 points for DLB and 12.0 points for PDD. These treatment effects were all significant compared to baseline (p < 0.001) but there were no significant between-group treatment differences (MMSE p = 0.56, NPI p = 0.39). UPDRS III motor scores did not change significantly from baseline values in either group. Although adverse effects were common (69%) they were usually mild and 64 patients (91%) completed the study. The four patients who did withdraw with adverse effects all had a PDD diagnosis.. Donepezil produced similar improvements in cognition and behaviour in DLB and PDD. This supports the hypothesis that the two disorders are closely related clinically and neurobiologically. Larger scale, placebo controlled clinical trials are needed to provide an evidence base to guide the clinical use of cholinesterase inhibitors in Lewy body disease.

Topics: Age Factors; Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Indans; Lewy Body Disease; Male; Neuropsychological Tests; Parkinson Disease; Piperidines; Severity of Illness Index; Treatment Outcome

Topics: Dementia; Donepezil; Down Syndrome; Humans; Indans; Nootropic Agents; Piperidines

A 58-year-old man presented with a history of disturbance in initiating gait. His history revealed meningoencephalitis five years prior to admission. Neurological examination included gait disturbance as difficulty in initiation and a hesitating speech with many freezing episodes and micrographia Magnetic resonance imaging (MRI) showed diffuse hyperintensity of frontal subcortical white matter on T2 weighted images. He was diagnosed with PA. L-Dopa up to the dosages of 1000 mg/ day and selegiline 10 mg/day were given. First brain SPECT using technetium-99m labeled D,L-hexamethylpropylene amine oxime (Tc-99m HMPAO) was performed when he was taking L-dopa and selegiline. In visual evaluation, hypoperfusion in bilateral frontoparietal cortex was seen (Fig. 2). Treatment with L-dopa and selegiline produced no benefit. Donepezil 10 mg/day was begun. This therapy regimen resulted in dramatic clinical improvement within several days that was confirmed by blinded raters who watched the patient's video recordings. During this response second brain perfusion SPECT study was repeated during donepezil therapy. Markedly increased perfusion in bilateral frontoparietal cortex was observed. This is the first case of PA to develop possibly after an episode of bacterial pneumococcal meningoencephalitis and who responded to donepezil as documented by changes in clinical findings and Tc-99m HMPAO brain SPECT studies.

Topics: Alexia, Pure; Brain; Cholinesterase Inhibitors; Dementia; Donepezil; Gait Disorders, Neurologic; Indans; Neurodegenerative Diseases; Piperidines; Radiopharmaceuticals; Recovery of Function; Syndrome; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

A number of recent studies surveying single nucleotide polymorphisms within the exonic regions of human genes have revealed a significant number of such variants, including many non-synonymous variants. This highlights the need to directly identify, within individual clinically well-defined patients, those variants that alter protein function as well as structure. We report on the development of a novel phenotypic screening process that combines high-throughput molecular cloning techniques with functional expression utilizing the cell-based assay R-SAT.. We applied the phenotypic screening process to an analysis of the m1 muscarinic acetylcholine receptor (CHRM1) gene in a cohort of 74 individuals, including 48 diagnosed with neurodegenerative disease, primarily Alzheimer disease, who have been stratified according to their clinical response to the acetylcholinesterase inhibitor donepezil. Phenotypic screening of the CHRM1 gene involved PCR-based amplification from genomic DNA and heterologous expression in mammalian cells.. Phenotypic screening yielded functional responses to the agonist carbachol displaying a mean potency (-pEC(50)+/- standard deviation) of 5.8 +/- 0.2, which did not differ from that observed with expression of the wild-type receptor gene (6.0 +/- 0.3). No altered levels of constitutive receptor activity were observed. Dideoxy sequencing did not reveal any non-synonymous variants in the coding exon of this gene within this clinical cohort, while detecting three synonymous variants.. The results confirm that the m1 receptor gene (CHRM1) is not highly polymorphic in the human population, suggesting that genetic variation within the coding exon of this gene is not a contributing factor to the clinical variability observed during treatment of dementia with cholinergic enhancement therapies.

Topics: Aged; Cholinesterase Inhibitors; Cohort Studies; Dementia; DNA; Donepezil; Drug Delivery Systems; Female; Genetic Testing; Humans; Indans; Male; Neurodegenerative Diseases; Nootropic Agents; Phenotype; Piperidines; Polymorphism, Genetic; Receptor, Muscarinic M1; Receptors, Muscarinic; Reverse Transcriptase Polymerase Chain Reaction

Topics: Adult; Cholinesterase Inhibitors; Dementia; Donepezil; Down Syndrome; Humans; Indans; Neuropsychological Tests; Pilot Projects; Piperidines; Treatment Outcome

Clinicians often encounter patients with dementia and urge incontinence who might benefit from both an anticholinergic medication and a cholinesterase inhibitor. At first glance, this combination would seem to violate basic principles of geriatric pharmacology, as the drugs appear to be working at cross-purposes and anticholinergic medications are notorious for worsening cognitive function in susceptible patients. A case is presented and discussed in which this combination was clinically effective and pharmacologically sound.

Topics: Aged; Benzhydryl Compounds; Cholinesterase Inhibitors; Cresols; Dementia; Donepezil; Drug Interactions; Drug Therapy, Combination; Female; Humans; Indans; Muscarinic Antagonists; Phenylpropanolamine; Piperidines; Tolterodine Tartrate; Urinary Incontinence

Topics: Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Indans; Male; Middle Aged; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine; Treatment Outcome

The case presented highlights the difficult differential diagnosis of dementia with parkinsonism. Many disorders affecting the frontal-subcortical circuits produce the triad of impaired cognition, movement disorder, and neuropsychiatric symptoms. The 72-year-old patient whose case is reviewed here had abnormalities in all three domains.

Topics: Aged; Brain; Dementia; Diagnosis, Differential; Donepezil; Fatal Outcome; Humans; Image Processing, Computer-Assisted; Indans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Nootropic Agents; Parkinson Disease; Piperidines; Psychiatric Status Rating Scales

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Indans; Mental Status Schedule; Nursing Homes; Piperidines

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Indans; Mental Status Schedule; Nursing Homes; Piperidines

Topics: Adult; Cholinesterase Inhibitors; Clinical Trials as Topic; Dementia; Donepezil; Down Syndrome; Female; Humans; Indans; Male; Middle Aged; Piperidines; Research Design; Sample Size

Memantine, a moderate-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be effective in dementia, including Alzheimer disease (AD). Therefore, its combination with acetylcholinesterase inhibitors (AChEIs) is anticipated. We report a postmarketing surveillance study conducted among German physicians who, during routine clinical practice, treated demented patients with memantine in combination with an AChEI. Most of the 158 surveyed patients (mean age, 74 years) were diagnosed with AD but other dementias were included. Memantine was prescribed at a wide range of daily doses (median, 20 mg/day) and was combined with donepezil for most patients (84%). Combination therapy was well tolerated for nearly all patients (98%) for an average observation period of 4 months at stable doses of both antidementia agents. No serious adverse drug reaction (ADR) was reported. No ADR or change in blood chemistry was experienced by most patients (96% and 81%, respectively); the six reported ADRs resolved without sequelae and without drug discontinuation. Global clinical status of most patients was judged as improved (54%) or stable (39%) over the observation period. These findings particularly suggest that memantine in combination with AChEIs is safe and well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Carbamates; Cholinesterase Inhibitors; Dementia; Donepezil; Dose-Response Relationship, Drug; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Humans; Indans; Memantine; Middle Aged; Phenylcarbamates; Piperidines; Product Surveillance, Postmarketing; Rivastigmine; Surveys and Questionnaires; Tacrine; Treatment Outcome

We report two cases of discontinuation syndrome on cessation of donepezil treatment. The clinical presentations are described and diagnostic criteria is appendixed.

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Humans; Indans; Middle Aged; Nootropic Agents; Piperidines; Substance Withdrawal Syndrome

In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a man with frontotemporal dementia (FTD). FTD most often presents with either a change in personality or behavior, such as social withdrawal, increased gregariousness, disinhibition, or obsessive behaviors; or with impairment of language function. Memory difficulties are common, but usually are less prominent than these other symptoms in the early stages of the disease. Frequently, psychiatric diagnoses are initially the primary consideration. Cases may be either familial or sporadic. In this familial case, an autopsy was ultimately performed and revealed findings characteristic of FTD, with grossly evident focal brain degeneration in the frontal and temporal regions, microscopic signs of gliosis, and cellular abnormalities of the intracellular microtubule-associated protein tau.

Topics: Age of Onset; Dementia; Donepezil; Fatal Outcome; Frontal Lobe; Humans; Indans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Nootropic Agents; Personality; Piperidines; tau Proteins; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Topics: Adult; Age Factors; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Down Syndrome; Female; Humans; Indans; Male; Middle Aged; Piperidines; Psychiatric Status Rating Scales

To define the actual knowledge of the impact of drugs for the treatment of dementia on the improvement of cognition in aging and mild cognitive impairment.. We conducted a Medline search for studies with the parameters drug and cognition. Only drugs that had demonstrated cognition improvements in dementia according to actual methodological standards were included. Drugs had to be approved in at least one American or European nation.. Donepezil, galantamine, Ginkgo biloba EGb 761 (definition see editorial), memantine and rivastigmine fulfilled these criteria. There were no systematic investigations on the effects of these drugs on cognition in healthy adults or patients with mild cognitive impairment (MCI). Regarding Ginkgo biloba, two studies on MCI patients could be identified. In healthy adults, we could only include one study investigating donepezil and seven investigating Ginkgo biloba EGb 761. According to the findings, donepezil significantly increased the percentage of REM sleep and REM density, whereas REM latency was reduced. This was interpreted as a sign of improved cognition. Ginkgo biloba EGb 761 improved cognition in healthy controls according to Delayed Free Recall and Delayed Recognition of the WAIS-III and the Color Naming of the Stroop Test as well as in MCI in Digit Copying, Dual Coding Task and speed of response on a computerized version of a classification task. The highest effects were observed after 6 weeks of treatment with 180 mg/d.. Due to the lack of standard procedures for investigating cognition improvement in healthy aging, results have to be interpreted cautiously. In healthy adults as well as in individuals categorized as having MCI, Ginkgo biloba EGb 761 improved cognition in some but not all neuropsychological tests. The single positive result with donepezil raises hope that other drugs may also contribute to cognitive improvement, even in healthy adults. However, the data do not allow any conclusions regarding an improvement following a specific "neuropsychological cluster." Studies on prevention have not been completed so far.

Topics: Adult; Aged; Aged, 80 and over; Aging; Cognition; Cognition Disorders; Dementia; Donepezil; Female; Galantamine; Ginkgo biloba; Humans; Indans; Male; MEDLINE; Middle Aged; Nootropic Agents; Piperidines; Plant Extracts

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Female; Hallucinations; Humans; Indans; Male; Mental Status Schedule; Piperidines; Treatment Outcome

Dementia treatment is one of the most important in home medical care. Donepezil hydrochloride, a dementia treatment drug available in Japan, is a symptomatic therapy but alleviates memory, willingness and feeling disorders and significantly improves QOL. Family doctors will be required to diagnose Alzheimer disease (AD) but it is very difficult for general physician to diagnose AD. This is the reason that the authors devised the simple criteria for diagnosing AD. Meanwhile, recent data from a multi-center study of donepezil hydrochloride for mild cognitive impairment (MCI) conducted in the US suggest that donepezil hydrochloride is also as useful for MCI as for AD. This is considered to suggest the significance to start treatment for AD at the early stage. Care for demented patients is not only the improvement of the apparent dementia. Recent scientific study data may be directly connected to treatment. These days, not a few elderly patients with dementia attend "Day-care Service" and the data indicate that rehabilitations they have under "Day-care Service" are important and useful. It is considered that non-pharmacological treatment may also play an important role and necessary to accumulate evidences in the future.

Topics: Aged; Alzheimer Disease; Dementia; Donepezil; Health Services for the Aged; Humans; Indans; Insurance, Health; Neuropsychological Tests; Nootropic Agents; Piperidines; Quality of Life

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Comorbidity; Dementia; Donepezil; Drug Therapy, Combination; Female; Humans; Indans; Mental Status Schedule; Middle Aged; Nootropic Agents; Parkinson Disease; Piperidines; Psychiatric Status Rating Scales; Risperidone; Schizophrenia

In studies of dementia, crossover designs are controversial, reflecting concerns about temporal stability of disease, confounding of treatment effects with period by treatment interactions and/or carryover effects. Carryover effects are differences in the lingering effect of treatments (placebo) into subsequent periods. In the context of a trial to study the effect of donepezil on dementia in patients with Parkinson's disease, we examine two-sequence crossover studies with two or four periods, and a four-sequence design with two periods. We quantify bias in estimated treatment effects due to carryover effects and explore the use of biased estimators in hypothesis testing. For hypothesis testing, type I error rates are valid if (1) repeated administration of treatment alters the outcome only for effective treatments and (2) carryover effects due to placebo following treatment periods are nonzero only for effective treatments. For crossover and parallel group designs, sample sizes are adjusted for reduced statistical power due to carryover effects and temporal changes in variance. For the proposed clinical study, we estimate that a single-period parallel group design with baselines would require 104 patients and take about 23 months to complete. A two-sequence, four-period parallel group design with baselines would require about 80 patients and about 20 months to complete. We conservatively assume a carryover effect of 50% of the treatment effect for a two-sequence four-period crossover design. The estimated treatment effect for this model may underestimate the true treatment effect by up to 13%. The sample size/study length requirements are 28 patients or 12.4 months, respectively, a substantial saving over either parallel group design. The cost of allowing for carryover in the sample size calculation is about 1.2 months of study time.

Topics: Bias; Cognition; Cross-Over Studies; Dementia; Donepezil; Effect Modifier, Epidemiologic; Humans; Indans; Nootropic Agents; Parkinson Disease; Piperidines; Randomized Controlled Trials as Topic; Research Design; Sample Size

To compare the prevalence of anticholinergic use in older adults with probable dementia with that of a matched comparison group of older adults who were unlikely to have dementia and to examine the extent to which patients taking donepezil concomitantly use anticholinergic medications.. Retrospective study.. Community-based older adults receiving medications through a pharmacy benefit management company.. Eight hundred thirty-six patients aged 65 and older. Patients taking donepezil (n = 418) constituted the treatment group. Patients not taking donepezil (n = 418) constituted the comparison group. Each treatment group member was matched with a comparison group member on the basis of age, sex, and number of drugs taken for chronic conditions.. The prevalence of anticholinergic use was compared in the treatment and comparison groups over a 3- to 12-month follow-up period using pharmacy claims data. The proportion of follow-up period days that treatment group members concomitantly used donepezil and anticholinergics was also examined.. Older adults with probable dementia were more likely to use anticholinergics than matched comparison group patients (33.0% vs 23.4%; P =.001). Of treatment group members receiving anticholinergics, 26.1% used multiple anticholinergic medications. Treatment group members who received anticholinergics used those drugs concomitantly with donepezil on a mean of 28.4% of follow-up period days.. Community-based, commercially insured, older adults with probable dementia are more likely to take anticholinergics than matched controls. Patients taking donepezil frequently use an anticholinergic medication concomitantly. This study suggests that prescribing for older adults with dementia could be improved, especially if cognitive enhancing agents are being considered.

Topics: Age Factors; Aged; Aged, 80 and over; Case-Control Studies; Cholinergic Antagonists; Cholinesterase Inhibitors; Contraindications; Dementia; Donepezil; Female; Humans; Indans; Male; Piperidines; Retrospective Studies

We investigated changes in the brain distribution of (-)-[(125)I]-m-iodovesamicol [(-)-[(125)I]mIV] in cholinergic denervation rats produced by a unilateral lesion of the nucleus basalis magnocellularis (NBM). Dual-tracer ex vivo autoradiographic analysis using (-)-[(125)I]mIV and [(99m)Tc]HMPAO was conducted to the effect of regional cerebral perfusion on the brain distribution of (-)-[(125)I]mIV in a unilateral NBM-lesioned rat. (-)-[(125)I]mIV binding in the ipsilateral cortex to the lesion significantly reduced by 10.4 %, compared with that in the contralateral cortex, while (-)-[(125)I]mIV binding in the ipsilateral caudate putamen, hippocampus and thalamus did not change. The rate of reduction in the (-)-[(125)I]mIV binding (10.4 %) was significantly higher than that of [(99m)Tc]HMPAO accumulation (4.0%) in the ipsilateral cortex to the lesion (P < 0.01). These results suggested that radioiodinated (-)-mIV may be useful in the study of dementia characterized by degeneration of the cholinergic neurotransmitter system, such as Alzheimer's disease.

Topics: Acetylcholine; Animals; Autoradiography; Brain; Dementia; Male; Piperidines; Radionuclide Imaging; Rats; Rats, Sprague-Dawley; Technetium Tc 99m Exametazime; Tissue Distribution

Primary progressive aphasia (PPA) is an uncommon neurodegenerative syndrome characterized by a relatively isolated dissolution of language function at the beginning, followed by deterioration of general cognitive function and of activities of daily living after 2 or more years. On account of neuropathological and clinical findings, PPA is supposed to form part of the spectrum of frontotemporal lobar degeneration. We present a case study of a 66-year-old woman with a probable fluent progressive aphasia. She initially experienced word amnesia and developed after 2 - 3 years gradual regression of word comprehension, over-fluent speech with semantic paraphasias, and at last generalized dementia. In addition to minor bilateral cortical volume reduction on CCT, MRI showed left temporal lobe atrophy involving hippocampus, SPECT revealed reduced uptake left frontal and temporal.

Topics: Aged; Aphasia, Primary Progressive; Atrophy; Brain; Dementia; Diagnosis, Differential; Donepezil; Female; Humans; Indans; Nootropic Agents; Piperidines; Radionuclide Imaging; Temporal Lobe; Treatment Outcome

In March 1998 the Department of Health and Social Services issued prescribing guidelines for the use of drugs for dementia. A criterion based audit of 202 consecutive cases was undertaken over one year which showed that the prescribing guidelines in general were being followed. A small number of patients, 3, were prescribed the drugs outside the guidelines and most failures, 10, were due to poor recording of data in the clinical record. Despite the recommendation of the DHSS no agreed shared care protocols have been implemented but this does not seem to have affected access to these drugs. As a result of this audit changes have been made with regard to documentation of patient assessments and suggestions made to review Clinical Resource Efficiency Support Team (CREST) guidelines.

Topics: Cholinesterase Inhibitors; Dementia; Donepezil; Drug Prescriptions; Drug Utilization; Follow-Up Studies; Guideline Adherence; Humans; Indans; Medical Audit; Piperidines; Practice Patterns, Physicians'

Topics: Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Hallucinations; Humans; Indans; Parkinson Disease; Piperidines; Treatment Outcome

Topics: Dementia; Donepezil; Humans; Indans; Nootropic Agents; Piperidines

Topics: Data Interpretation, Statistical; Dementia; Donepezil; Humans; Indans; Nootropic Agents; Piperidines; Practice Guidelines as Topic

Topics: Age Factors; Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Hallucinations; Humans; Indans; Male; Piperidines; Visual Perception

Topics: Cognition; Dementia; Donepezil; Humans; Indans; Nootropic Agents; Piperidines

Topics: Aged; Antipsychotic Agents; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Therapy, Combination; Humans; Indans; Male; Parkinson Disease; Piperidines; Risperidone

What ethical concerns regarding the application of new antidementia compounds are pertinent to the best interests of patients with Alzheimer's disease and their caregivers? Based on collected preliminary anecdotal accounts, these concerns are important and should be considered carefully by clinicians, researchers, and families.

Topics: Aged; Alzheimer Disease; Beneficence; Cholinesterase Inhibitors; Dementia; Donepezil; Ethics, Medical; Female; Humans; Indans; Male; Nootropic Agents; Patient Care Planning; Piperidines; Professional-Family Relations; Quality of Life; Risk Assessment; Withholding Treatment

Topics: Alzheimer Disease; Dementia; Diagnosis, Differential; Donepezil; Humans; Indans; Neurology; Nootropic Agents; Parkinson Disease; Piperidines; Psychiatry; Societies, Medical

Topics: Aged; Brain; Delirium; Dementia; Donepezil; Humans; Indans; Lewy Bodies; Magnetic Resonance Imaging; Male; Nootropic Agents; Piperidines; Psychiatric Status Rating Scales

Topics: Aged; Bipolar Disorder; Dementia; Donepezil; Drug Therapy, Combination; Female; Humans; Indans; Middle Aged; Nootropic Agents; Piperidines

Delirium is a common complication of dementia and may produce considerable morbidity. In addition to psychotic symptoms such as hallucinations and delusions, delirium may produce considerable agitation, which may be refractory to conventional medications such as antipsychotics and benzodiazepines. The main approach to delirium is to treat any underlying medical problem that could cause the delirium. However, delirium is not always reversible, and there is no specific treatment for persistent delirium. The authors present a case of delirium complicating a preexisting dementia that resolved rapidly following initiation of the cholinesterase inhibitor donepezil, suggesting that cholinergic dysfunction may have played a role in the etiology of this patient's delirium. Future research needs to be directed at the issue of cholinergic activity in delirium through monitoring of serum anticholinergic activity and its response to procholinergic therapy.

Topics: Aged; Alcohol Withdrawal Delirium; Cholinesterase Inhibitors; Cognition Disorders; Delirium; Dementia; Donepezil; Humans; Indans; Male; Mood Disorders; Piperidines; Treatment Outcome

Topics: Advertising; Cholinesterase Inhibitors; Dementia; Donepezil; Drug Industry; Humans; Indans; Piperidines

Topics: Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Health Policy; Humans; Indans; Piperidines

Topics: Aged; Antipsychotic Agents; Dementia; Evoked Potentials, Visual; Hallucinations; Humans; Isoxazoles; Magnetic Resonance Imaging; Male; Piperidines; Risperidone; Visual Cortex

Topics: Aged; Antipsychotic Agents; Dementia; Female; Humans; Isoxazoles; Male; Piperidines; Risperidone

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Dementia; Dementia, Vascular; Female; Humans; Isoxazoles; Male; Piperidines; Psychotropic Drugs; Risperidone; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Dementia; Female; Humans; Isoxazoles; Lewy Bodies; Male; Middle Aged; Parkinson Disease; Piperidines; Risperidone

A series of 1-ar(o)yl-3-[2-(1-benzyl-4-piperidinyl)ethyl](thio)urea derivatives was synthesized and evaluated for antiacetylcholinesterase activity. Most aroyl(thio)urea derivatives showed potent inhibitory activity in the sub-micromolar range. A comparable potency was obtained with the aryl(thio)urea analogues by replacing the phenyl with a 2-pyridyl group. The substituted guanidine variations proved to be almost inactive whereas the nitroethylene analogues appeared to be quite efficient. These results were interpreted in terms of the preferential cis-trans conformation of the aroyl(thio)urea and 2-pyridyl(thio)urea moieties involving the existence of hydrogen bonding. In vivo experiments showed that compound 7m had maximal antiamnestic activity at 0.03 mg/kg with a therapeutic ratio greater than 1000, while cholinergic side effects were only seen at doses 100-fold the maximally effective antiamnestic dose. Compound 7m represents a potentially interesting antidementia agent.

Topics: Acetylcholinesterase; Amnesia; Animals; Avoidance Learning; Cholinesterase Inhibitors; Dementia; Dose-Response Relationship, Drug; Hydrogen Bonding; Mice; Molecular Conformation; Molecular Structure; Piperidines; Rats; Scopolamine; Structure-Activity Relationship; Thiourea

Topics: Adult; Aged; Alanine Transaminase; Bipolar Disorder; Blood Pressure; Blood Sedimentation; Butyrophenones; Creatinine; Dementia; Electrocardiography; Female; Hemoglobinometry; Humans; Leukocyte Count; Long-Term Care; Male; Middle Aged; Neurocognitive Disorders; Paranoid Disorders; Piperidines; Schizophrenia; Time Factors; Tranquilizing Agents

Topics: Amines; Antiparkinson Agents; Basal Ganglia; Butyrophenones; Dementia; Female; Gait; Haloperidol; Humans; Middle Aged; Movement Disorders; Phenothiazines; Piperidines; Posture

Topics: Antidepressive Agents; Cognition Disorders; Dementia; Depression; Humans; Hysteria; Indoles; Male; Paranoid Disorders; Piperidines; Schizophrenia; Schizophrenic Psychology

Topics: Chlorpromazine; Dementia; Humans; Mental Disorders; Opium; Piperidines; Psychopharmacology; Psychotic Disorders; Reserpine

Topics: Dementia; Double-Blind Method; Humans; Mental Disorders; Piperidines; Psychotic Disorders