topiramate and Alzheimer-Disease

Capgras delusion (CD) has multiple etiologies including neurodegenerative disorders and can be associated with violent behavior. CD is a common complication of Alzheimer dementia (AD); however, CD with violent behavior is uncommon in AD. We report escalating violent behavior by a patient with advanced AD and CD who presented to the emergency department (ED) and required admission to an academic medical center.. Case analysis with PubMed literature review.. A 75-year-old male with a 13-year history of progressive AD, asymptomatic bipolar disorder, chronic kidney disease, hypertension, hyperlipidemia, and benign prostatic hypertrophy presented to the ED with recurrent/escalating violence toward his wife, whom he considered an impostor. His psychotropic regimen included potentially inappropriate medications (PIMs) for geriatric/AD patients-topiramate/amitriptyline/chlordiazepoxide/olanzapine-that are associated with delirium, cognitive decline, dementia, and mortality. Renal dosing for topiramate, reduction in PIMs/anticholinergic burden, and substituting haloperidol for olanzapine resolved his violent behavior and CD.. CD in AD is a risk factor for violent behavior. As the geriatric population in the United States grows, CD in patients with AD may present more frequently in the ED, requiring proper treatment. Pharmacovigilance is necessary to minimize PIMs in geriatric/AD patients. Clinicians and other caregivers require further education to appropriately address CD in AD.

Topics: Aged; Aggression; Alzheimer Disease; Amitriptyline; Anticonvulsants; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Capgras Syndrome; Chlordiazepoxide; Fructose; Haloperidol; Humans; Hypnotics and Sedatives; Male; Olanzapine; Potentially Inappropriate Medication List; Renal Insufficiency, Chronic; Topiramate; Violence

Behavioral disturbances are determining factors in handling patients with Alzheimer dementia. The current pharmacotherapy for behavioral symptoms associated with dementia is not satisfactory. Our goal was to compare a new anticonvulsant, topiramate, with a usually used medication, risperidone, for controlling behavioral disturbances of patients with Alzheimer dementia.. Elderly patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of Alzheimer disease and significant behavioral disturbances were randomized to receive, for a period of 8 weeks, a flexible dose of either topiramate (25-50 mg/d) or risperidone (0.5-2 mg/d). Outcome measures were the Cohen-Mansfield Agitation Inventory, Neuropsychiatry Inventory parts 1 and 2, and the Clinical Global Impression.. Forty-eight patients were randomized to treatment with either topiramate or risperidone, and 41 patients (21 of 25 in topiramate group and 20 of 23 in risperidone group) completed the trial. Both groups showed significant improvement in all outcome measures without important difference (Neuropsychiatry Inventory total score P < 0.531, Z = 0.62; Cohen-Mansfield Agitation Inventory P < 0.927, Z = 0.09; Clinical Global Impression, P < 0.654, Z = 0.48). There were no significant changes in the cognitive status of patients (assessed by Mini-Mental Status Examination) taking topiramate or risperidone during the trial.. Treatment with a low dose of topiramate (25-50 mg/d) demonstrated a comparable efficacy with risperidone in controlling behavioral disturbances of patients with Alzheimer dementia.

Topics: Aged; Alzheimer Disease; Anticonvulsants; Antipsychotic Agents; Behavioral Symptoms; Caregivers; Double-Blind Method; Female; Fructose; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Risperidone; Topiramate; Treatment Outcome

Alzheimer's disease (AD) is a neurodegenerative disease that is the main cause of dementia in the elderly. The aggregation of β-amyloid peptides is one of the characterizing pathological changes of AD. Topiramate is an antiepileptic drug, which in addition, is used in the treatment of many neuropsychiatric disorders. In this study, the therapeutic effects of topiramate were investigated in a transgenic mouse model of cerebral amyloidosis (APP/PS1 mice). Before, during, and after topiramate treatment, behavioral tests were performed. Following a treatment period of 21 days, topiramate significantly ameliorated deficits in nest-constructing capability as well as in social interaction. Thereafter, brain sections of mice were analyzed, and a significant attenuation of microglial activation as well as β-amyloid deposition was observed in sections from topiramate-treated APP/PS1 mice. Therefore, topiramate could be considered as a promising drug in the treatment of human AD.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Amyloidosis; Animals; Anticonvulsants; Behavior, Animal; Disease Models, Animal; Male; Mice; Mice, Transgenic; Molecular Structure; Protein Aggregates; Protein Aggregation, Pathological; Topiramate

Alzheimer's disease is an age-related neurodegenerative disease and a synaptic function defect disease, the clinical symptoms are mainly progressive cognitive impairment, affecting patient's social function. Aim of this report was to investigate the effect of topiramate on apoptosis-related protein expression (Bcl-2, Survivin, Fas, Bax and Caspase-3) in the hippocampus of a rat model with Alzheimers Disease (AD).. Thirty-six adult Wistar rats were randomly divided into a control group, a model group and a test group. A dose of amyloid beta-protein 1-40 (Aβ1-40) was injected into the hippocampus of the rats in the model and test groups, and the control rats are injected with same amount of saline. After AD model was successfully established, the rats in each group were administrated with an i.p. injection of topiramate (20 mg/kg/d) for 30 days. The effect of topiramate on the apoptosis-related protein levels in hippocampus neurons was studied by immunohistochemistry.. The number of Bcl-2 and Survivin positive cells and optical density in hippocampus of rats in test group was more than those of rats in model groups, but less than those of rats in control group (p < 0.01); Fas, Bax and Caspase-3 positive cells and optical density in hippocampus of rats in test group was less than those of rats in the model group, but more than those of rats in control group (p < 0.01).. Alzheimer's disease can induce apoptosis of hippocampus neurons in rats. Topiramate can prevent apoptosis of hippocampus neurons, at least in part, by increasing expression of Bcl-2 and Survivin and decreasing expression of Fas, Bax and Caspase-3.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Caspase 3; Disease Models, Animal; fas Receptor; Fructose; Hippocampus; Male; Microtubule-Associated Proteins; Peptide Fragments; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Survivin; Topiramate

The close relationship between epileptic seizure and Alzheimer's disease (AD) has been demonstrated in the past decade. Valproic acid, a traditional first-line antiepileptic drug, exerted protective effects in transgenic models of AD. It remains uncertain whether new antiepileptic drugs could reverse neuropathology and behavioral deficits in AD transgenic mice.. APPswe/PS1dE9 transgenic mice were used in this study, which over express the Swedish mutation of amyloid precursor protein together with presenilin 1 deleted in exon 9. 7-month-old APPswe/PS1dE9 transgenic mice were treated daily with 20 mg/kg topiramate (TPM) and 50 mg/kg levetiracetam (LEV) for 30 days by intraperitoneal injection to explore the effects of TPM and LEV on the neuropathology and behavioral deficits.. The results indicated that TPM and LEV alleviated behavioral deficits and reduced amyloid plaques in APPswe/PS1dE9 transgenic mice. TPM and LEV increased Aβ clearance and up-regulated Aβ transport and autophagic degradation. TPM and LEV inhibited Aβ generation and suppressed γ-secretase activity. TPM and LEV inhibited GSK-3β activation and increased the activation of AMPK/Akt activation. Further, TPM and LEV inhibited histone deacetylase activity in vivo.. Therefore, TPM and LEV might have the potential to treat AD effectively in patient care.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Anticonvulsants; Brain; Cell Line, Tumor; Fructose; Humans; Levetiracetam; Maze Learning; Mice; Mice, Transgenic; Neuroprotective Agents; Piracetam; Presenilin-1; Topiramate

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Anticonvulsants; Antipsychotic Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fructose; Humans; Retrospective Studies; Risperidone; Topiramate; Treatment Outcome