2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Cognition-Disorders

The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer's disease (AD).. We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB.. The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid beta (abeta) isoforms as well as alpha-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level.. Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.

Topics: Aged; alpha-Synuclein; Alzheimer Disease; Biomarkers; Cognition Disorders; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Early Diagnosis; Electroencephalography; Humans; Iodine Radioisotopes; Lewy Body Disease; Neuropsychological Tests; Phosphorylation; Positron-Emission Tomography; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes; Ubiquitin

Numerous animal studies and clinical trials have demonstrated that erythropoietin (EPO) has therapeutic effects in ischemic and degenerative diseases. However, few clinical trials have investigated the effect of EPO in Parkinson's disease (PD) patients. This study was an exploratory pilot study to investigate the effects of recombinant human EPO (rhEPO) on motor and non-motor symptoms (NMS) in PD patients.. A total of 26 PD patients at the Hanyang University Hospital were enrolled in the study. The participants were randomly assigned to rhEPO and placebo groups. The rhEPO group was infused intravenously (40,000 IU each) twice a week for 5 weeks. Clinical improvement was estimated using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), the NMS Scale (NMSS) and the 39-Item Parkinson's Disease Questionnaire (PDQ-39). [(18)F] N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) photon emission tomography (PET) scanning was performed on each participant at baseline and again after 12 months.. The rhEPO administration significantly improved the NMSS and PDQ-39 scores at 12 months. The UPDRS-III, which reflects motor function, did not change significantly after the rhEPO treatment. With the NMSS, the domains of cardiovascular autonomic function, sleep/fatigue, mood/cognition and attention/memory showed significant changes. None of the participants experienced any serious adverse effects.. We found that rhEPO had beneficial effects on NMS but not on motor function. Dopaminergic refractory NMS, such as cardiovascular autonomic dysfunction and cognition, showed improvement after the administration of rhEPO. Our results suggest that rhEPO might be a good candidate for the treatment of NMS in PD patients.

Topics: Aged; Aged, 80 and over; Brain; Cognition Disorders; Erythropoietin; Female; Humans; Male; Mental Disorders; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Prospective Studies; Single-Blind Method; Sleep Wake Disorders; Surveys and Questionnaires; Time Factors; Tomography, X-Ray Computed; Tropanes; Vascular Diseases

Both movement (MD) and cognitive (CD) disorders can occur associated in some neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD).. We further investigated the usefulness of 123I-Ioflupane SPECT and 18F-FDG PET combined use in patients with these disorders in the early stage.. We retrospectively enrolled twenty-five consecutive patients with MD and CD clinical symptoms of recent appearance. All patients had undergone neurologic examination, neuropsychological tests, and magnetic resonance imaging. 123I-Ioflupane SPECT was performed in all cases, followed by 18F-FDG PET two weeks later. In the two procedures, both qualitative (QL) and quantitative (QN) image analyses were determined.. In patients with both 123I-Ioflupane SPECT and 18F-FDG PET pathologic data, associated dopaminergic and cognitive impairments were confirmed in 56% of cases. Pathologic SPECT with normal PET in 16% of cases could diagnose MD and exclude an associated CD, despite clinical symptoms. On the contrary, normal SPECT with pathologic PET in 28% of cases could exclude basal ganglia damage while confirming CD. QN 123I-Ioflupane SPECT analysis showed better performance than QL since QN correctly characterized two cases of MD with normal QL. Moreover, correct classification of normal metabolism was made only by QN analysis of 18F-FDG PET in four cases, despite suspect areas of hypometabolism at QL.. The combined use of these imaging procedures proved a reliable diagnostic tool to accurately identify and characterize MD and CD in early stage. QN analysis was effective in supporting QL evaluation, and its routine use is suggested, especially with inconclusive QL.

Topics: Alzheimer Disease; Brain; Cognition Disorders; Fluorodeoxyglucose F18; Humans; Movement Disorders; Neurodegenerative Diseases; Nortropanes; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tomography, Emission-Computed, Single-Photon

Traumatic brain injury can reduce striatal dopamine levels. The cause of this is uncertain, but is likely to be related to damage to the nigrostriatal system. We investigated the pattern of striatal dopamine abnormalities using 123I-Ioflupane single-photon emission computed tomography (SPECT) scans and their relationship to nigrostriatal damage and clinical features. We studied 42 moderate-severe traumatic brain injury patients with cognitive impairments but no motor parkinsonism signs and 20 healthy controls. 123I-Ioflupane scanning was used to assess dopamine transporter levels. Clinical scan reports were compared to quantitative dopamine transporter results. Advanced MRI methods were used to assess the nigrostriatal system, including the area through which the nigrostriatal projections pass as defined from high-resolution Human Connectome data. Detailed clinical and neuropsychological assessments were performed. Around 20% of our moderate-severe patients had clear evidence of reduced specific binding ratios for the dopamine transporter in the striatum measured using 123I-Ioflupane SPECT. The caudate was affected more consistently than other striatal regions. Dopamine transporter abnormalities were associated with reduced substantia nigra volume. In addition, diffusion MRI provided evidence of damage to the regions through which the nigrostriatal tract passes, particularly the area traversed by dopaminergic projections to the caudate. Only a small percentage of patients had evidence of macroscopic lesions in the striatum and there was no relationship between presence of lesions and dopamine transporter specific binding ratio abnormalities. There was also no relationship between reduced volume in the striatal subregions and reduced dopamine transporter specific binding ratios. Patients with low caudate dopamine transporter specific binding ratios show impaired processing speed and executive dysfunction compared to patients with normal levels. Taken together, our results suggest that the dopaminergic system is affected by a moderate-severe traumatic brain injury in a significant proportion of patients, even in the absence of clinical motor parkinsonism. Reduced dopamine transporter levels are most commonly seen in the caudate and this is likely to reflect the pattern of nigrostriatal tract damage produced by axonal injury and associated midbrain damage.

Topics: Adult; Aged; Brain; Brain Injuries, Traumatic; Cognition Disorders; Diagnostic Uses of Chemicals; Dopamine; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Nortropanes; Tomography, Emission-Computed, Single-Photon; Young Adult

To investigate whether diabetes mellitus is associated with Parkinson-like pathology in people without Parkinson disease and to evaluate the effect of diabetes mellitus on markers of Parkinson pathology and clinical progression in drug-naive patients with early-stage Parkinson disease.. We compared 25 patients with Parkinson disease and diabetes mellitus to 25 without diabetes mellitus, and 14 patients with diabetes mellitus and no Parkinson disease to 14 healthy controls (people with no diabetes mellitus or Parkinson disease). The clinical diagnosis of diabetes mellitus was confirmed by 2 consecutive fasting measurements of serum glucose levels >126 mL/dL. Over a 36-month follow-up period, we then investigated in the population with Parkinson disease whether the presence of diabetes mellitus was associated with faster motor progression or cognitive decline.. The presence of diabetes mellitus was associated with higher motor scores (. Diabetes mellitus may predispose toward a Parkinson-like pathology, and when present in patients with Parkinson disease, can induce a more aggressive phenotype.

Topics: Adult; Aged; alpha-Synuclein; Blood Glucose; Cognition Disorders; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Longitudinal Studies; Male; Middle Aged; Motor Disorders; Parkinson Disease; tau Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

To investigate whether REM sleep behavior disorder (RBD) is associated with worse motor and cognitive decline in Parkinson disease (PD) METHODS: Four-hundred twenty-one drug-naive patients with early-stage PD and 196 controls without PD were included in this study. All participants underwent a [. At cross-sectional analyses, patients with PD and probable RBD (PD-RBD) had lower CSF β-amyloid 1-42 (Aβ. The presence of RBD in PD is associated with faster motor progression in patients with greater synuclein and dopaminergic pathology, and with higher risk of cognitive decline in patients with greater synuclein and amyloid pathology. Our findings provide an important direction toward understanding phenotypes and their prognosis in PD.

Topics: Aged; Aged, 80 and over; alpha-Synuclein; Amyloid beta-Peptides; Brain; Cognition Disorders; Cohort Studies; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Peptide Fragments; REM Sleep Behavior Disorder; Severity of Illness Index; Statistics, Nonparametric; tau Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Discrete patterns of progression have been suggested for patients with Parkinson disease and presenting tremor dominant (TD) or postural instability gait disorders (PIGD). However, longitudinal prospective assessments need to take into consideration the variability in clinical manifestations and the evidence that only 40% of initially classified PIGD remain in this subtype at subsequent visits.. We analyzed clinical progression of PIGD compared to TD using longitudinal clinical data from the PPMI. Given the reported instability of such clinical classification, we only included patients who were reported as PIGD/TD at each visit during the 4-year observation. We used linear mixed-effects models to test differences in progression in these subgroups in 51 dependent variables.. There were 254 patients with yearly assessment. The number of PIGD was 36/254 vs 144/254 TD. PIGD had more severe motor disease at baseline but progressed faster than TD only in three non-motor items of the MDS-UPDRS: cognitive impairment, hallucinations, and psychosis plus features of DDS. Our analysis also showed in PIGD faster increase in the average time with dyskinesia.. PIGD are characterized by more severe disease manifestations at diagnosis and greater cognitive progression, more frequent hallucinations, psychosis as well as features of DDS than TD patients. We interpret these findings as expression of greater cortical and subcortical involvement in PIGD already at onset. Since PIGD/TD classification is very unstable at onset, our analysis based on stricter definition criteria provides important insight for clinical trial stratification and definition of related outcome measures.

Topics: Adult; Aged; Cognition Disorders; Databases, Factual; Disease Progression; Female; Gait Disorders, Neurologic; Humans; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Nortropanes; Parkinson Disease; Psychiatric Status Rating Scales; Severity of Illness Index; Surveys and Questionnaires

The p.A53T point mutation in the α-synuclein gene (SNCA) is a rare but highly relevant cause of autosomal dominant Parkinson's disease (PD).. The objective of this study was to assess striatal dopaminergic denervation in a cohort of symptomatic carriers of the p.A53T SNCA mutation as compared to PD patients.. Data from the Parkinson's Progression Markers Initiative database of 11 symptomatic p.A53T SNCA mutation carriers who underwent 123I-FP-CIT SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging at our site were compared with those of 33 age-, sex-, and disease duration-matched PD patients.. The p.A53T mutation carriers had significantly lower caudate nucleus binding ratio both contralaterally and ipsilaterally to the most affected side (P = .002 and P = .006) and a decreased contralateral caudate/putamen signal ratio (P = .007) as compared to PD. A similar degree of striatal asymmetry was observed in both subgroups. No correlation between scores in neuropsychological tests and caudate nucleus dopaminergic denervation could be demonstrated.. PD patients harboring the p.A53T SNCA mutation show evidence of a more severe nigrostriatal denervation, especially evident in the caudate nucleus. The lack of significant differences in the putaminal binding ratios may reflect a floor effect or a true preferential targeting of the caudate terminals in p.A53T SNCA-associated PD. © 2018 International Parkinson and Movement Disorder Society.

Topics: Adult; Alanine; alpha-Synuclein; Cognition Disorders; Cohort Studies; Corpus Striatum; Dopamine; Female; Functional Laterality; Humans; Male; Middle Aged; Mutation; Parkinson Disease; Threonine; Tomography, Emission-Computed, Single-Photon; Tropanes

To produce coordinated manual actions within specific space and time, their relationship must be properly dealt with in a sensorimotor system. This study examined how such a coordination system might be impaired in normal aging and in Parkinson's disease (PD). Using a tablet device, young participants, elderly participants, and patients with PD were tested for concurrent production of distance and duration as well as single production of distance or duration alone. Results were analyzed in relation to deficiency of presynaptic dopamine transporter (DaT) in the striatum. We observed different patterns of impairment between normal aging and PD. Elderly participants exhibited duration overproduction when they had to produce distance and duration concurrently, but were normal in single production of either distance or duration. In contrast, PD patients exhibited normal distance production and marked underproduction of duration when either distance or duration was produced alone, but both duration and distance were underproduced when they were concurrently produced. These findings suggest that aging yields impaired performances in both elderly people and PD patients, but that temporal underproduction in PD patients entrains spatial production as if the distance to be produced were made consistent with their duration underproduction. We also observed that striatal DaT deficit was correlated with the extent of duration underproduction in PD patients. The deficit may be associated with the severe time compression and the entrainment during spatiotemporal production in PD patients.

Topics: Age Factors; Aged; Analysis of Variance; Cognition Disorders; Corpus Striatum; Feedback; Female; Functional Laterality; Humans; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Perceptual Disorders; Spatial Navigation; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

To investigate whether dopamine transporter (DAT) binding, as measured with single photon emission computed tomography (SPECT), can be used to predict mortality in patients with Parkinson's disease (PD).. A total of 162 patients with PD and abnormal [I-123]FP-CIT SPECT were clinically followed for a median of 5.8 years. A multivariate Cox regression model was used to investigate survival with the independent predictors of age, gender, severity of motor impairment, levodopa-equivalent daily dose of medication, presence of cognitive defects, and putaminal specific binding ratio (SBR) of [I-123]FP-CIT. In addition, associations between striatal and extrastriatal SBRs and survival were investigated using voxel-based analyses.. The overall mortality was 25.9%, and the Kaplan-Meier estimate for mortality was 36%. Older age (P < 0.001), presence of cognitive defects (P = 0.001), and more severe motor symptom severity (P = 0.002) were significantly associated with increased mortality. No associations were found between putaminal DAT binding and survival (P = 0.99). There were no significant differences in SBRs in any striatal or extrastriatal region between survivors and non-survivors, and no associations were found between SBRs and scan-to-death intervals among non-survivors.. Unlike the severity of motor and cognitive symptoms, the level of striatal dopaminergic defect in DAT SPECT does not predict mortality in PD. Although presynaptic dopaminergic functional imaging may have value as a diagnostic tool, the clinical symptom-based characteristics are superior for predicting lifespan.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Motor Activity; Parkinson Disease; Protein Binding; Retrospective Studies; Survival; Tomography, Emission-Computed, Single-Photon; Tropanes

Cognitive impairment is a frequent and disabling feature of Parkinson's disease. Identifying the factors able to predict cognitive worsening since the early stage may improve disease management. The objective of this study was to define the best predictors of future cognitive worsening in a group of patients with newly diagnosed PD and to propose cutoff values potentially useful at the individual level.. Step-wise logistic regression selected the posterior qEEG mean frequency and. Resting EEG and

Topics: Aged; Cognition Disorders; Electroencephalography; Female; Humans; Logistic Models; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Predictive Value of Tests; ROC Curve; Severity of Illness Index; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

Aging is the most important risk factor of development of dementia in Parkinson's disease (PD), but there are no data on clinical and radiological heterogeneity of PD dementia (PDD) depending on age at onset.. The goal of this study was to examine whether patients with PDD are clinically and radiologically heterogeneous depending on age at onset.. A total of 116 patients with PD dementia and 121 age- and sex-matched normal controls were enrolled. The subjects were divided into early-onset (EOPDD; n = 39) and late-onset (LOPDD; n = 77) PDD with the respective age-matched control group based on a cutoff value of 70 years. The effects of diagnosis, age, and their interaction on neuropsychological tests, cortical thickness, and substantia innominata volume were assessed using analysis of covariance.. EOPDD patients had a poorer cognitive performance on digit backward, forward span test (p = 0.011 and 0.05), and visual recognition memory function (p = 0.012) compared with LOPDD patients. Additionally, EOPDD patients exhibited cortical thinning in the left anterior cingulate gyrus and the right inferior temporal gyrus, with significantly decreased normalized substantia innominata volume (p = 0.044).. Our data demonstrated that EOPDD patients exhibit poorer cognitive performance and more severe atrophy in the cortex and substantia innominata, implying that EOPDD may be a distinct phenotype different from LOPDD.

Topics: Age of Onset; Aged; Case-Control Studies; Cerebral Cortex; Cognition Disorders; Dementia; Female; Fluorine Radioisotopes; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Statistics, Nonparametric; Tropanes

Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies.. Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([(123) I]FP-CIT). Associations between striatal binding ratios and motor (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini-Mental State Examination [MMSE] and neuropsychological tests) symptoms were assessed by linear regression analysis.. The explorative analysis showed that the motor UPDRS was negatively associated with putamen dopamine transporter binding, whereas no association with striatal dopamine transporter binding was found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE scores. However, in post-hoc analysis, executive impairment was positively associated with dopamine transporter loss after adjustment of age and gender.. Dopamine deficiency in patients with dementia with Lewy bodies was associated with severity of motor symptoms, but did not correlate significantly with ratings of neurobehavioral disturbances or overall cognition.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Fluorine Radioisotopes; Humans; Lewy Body Disease; Linear Models; Male; Mental Disorders; Mental Status Schedule; Motor Activity; Protein Binding; Tomography, Emission-Computed, Single-Photon; Tropanes

To explore the microstructural integrity of the optic nerve and its role as a cognitive predictor in patients with de novo Parkinson's disease (PD) using diffusion tensor image-based magnetic resonance scans.. We enrolled 82 patients with de novo PD, 36 patients with drug-induced parkinsonism (DIP), and 36 controls. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured on the mid-portion of the intraorbital optic nerve. Using a multivariate analysis of variance with repeated measures, longitudinal changes in cognitive subscores of a comprehensive neuropsychological test were evaluated in PD patients according to optic nerve integrity.. The mean FA value in PD was significantly lower (0.552 ± 0.103, p < 0.001) than that in DIP (0.645 ± 0.099) or the controls (0.689 ± 0.089), whereas the mean ADC value was significantly higher in the PD group compared to the DIP or control group (p < 0.001). Optic nerve integrity was not associated with parkinsonian motor severity, striatal dopamine transporter activity, olfaction, or baseline cognitive performance in PD patents. In a longitudinal assessment of cognition in PD, the lower FA group showed significant decline in the performance of Clock Drawing Test (F = 3.39, p = 0.038), but no significant differences in the other cognitive subsets.. This study demonstrated that microstructural integrity in the optic nerve was distorted in PD patients, and that this nerve integrity might act as a cognitive predictor of visuospatial dysfunction.

Topics: Aged; Anisotropy; Cognition Disorders; Diffusion Tensor Imaging; Female; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Neuropsychological Tests; Optic Nerve; Parkinson Disease; Positron-Emission Tomography; Retrospective Studies; Spatial Processing; Statistics as Topic; Tropanes

There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.

Topics: Aged; alpha-Synuclein; Cognition Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Gene Expression Regulation; Genetic Testing; Humans; Male; Microarray Analysis; Middle Aged; Neuroimaging; Parkinson Disease; Radionuclide Imaging; RNA, Messenger; Severity of Illness Index; Tropanes

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [(123) I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD.

Topics: Adult; Aged; Aged, 80 and over; Cognition Disorders; Corpus Striatum; Cross-Sectional Studies; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Basal Ganglia Diseases; Brain; Calcinosis; Cognition Disorders; Diagnosis, Differential; Female; Humans; Middle Aged; Movement Disorders; Nortropanes; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Hyposmia is highly prevalent in the motor phase of Parkinson's disease (PD) and is an established pre-motor sign of PD that may precede the onset of motor symptoms by as long as 5 years. The data presented here are part of an ongoing study to determine the relationship of the olfactory deficit in PD with both motor and non-motor features of the disease. The study population so far includes 96 patients with a clinical diagnosis of PD (UK PD Society Brain Bank criteria; mean age 64.9 years; mean disease duration 4.8 years). Olfactory testing was performed using the 40-item UPSIT. We analyzed the relationship between UPSIT scores and measures of motor (disease duration, stage and severity) and non-motor (cognitive function, depression, anxiety and sleep) function. In 60 PD patients, [(123)I]FP-CIT SPECT scans were available to assess the relationship between UPSIT scores and striatal dopamine transporter (DAT) binding. Preliminary analyses revealed correlations of the olfactory deficit in PD with both motor and non-motor features, as well as with striatal DAT binding. These data suggest that the olfactory deficit in PD is not stationary by the time the motor phase is entered, but continues to progress over time. Hyposmia may therefore be useful as a marker of disease progression, at least in the early disease stages.

Topics: Aged; Anxiety; Cognition Disorders; Corpus Striatum; Depression; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Olfaction Disorders; Parkinson Disease; Protein Binding; Severity of Illness Index; Sleep Wake Disorders; Tomography, Emission-Computed, Single-Photon; Tropanes

The purpose of this study is to compare the neuropsychological profile of patients affected by parkinsonism and vascular lesions to that in patients with PD alone (PD) and to evaluate whether the brain vascular lesion load is associated with neuropsychological variables. Thirty-six nondemented patients with parkinsonism were divided into 3 groups of 12 patients each, according to both clinical history and the presence of brain vascular lesions and/or dopaminergic denervation as revealed by magnetic resonance and dopamine transporter imaging, respectively. The first group had vascular lesions without dopaminergic denervation (VP group); the second group had vascular lesions and dopaminergic denervation (DD) (VP+DD group); and the third group consisted of patients with dopaminergic denervation (PD group) without vascular lesions. All patients underwent neurological and neuropsychological assessments. The groups differed in disease duration, age at onset, and cerebrovascular risk factors. The VP and VP+DD groups performed worse than the PD group on frontal/executive tasks. Regardless of the presence of dopaminergic denervation, cerebrovascular lesions in hemispheric white matter, basal ganglia, and cerebellum have an important effect in determining early onset and severity of cognitive impairment in patients with parkinsonism.

Topics: Aged; Cerebrovascular Disorders; Cognition Disorders; Executive Function; Female; Frontal Lobe; Humans; Magnetic Resonance Imaging; Male; Memory; Mental Status Schedule; Middle Aged; Neurologic Examination; Neuropsychological Tests; Parkinsonian Disorders; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

To unveil cognitive-nigrostriatal correlations in Parkinson's disease (PD), 30 de novo, drug-naïve PD patients and 15 patients with essential tremor (Controls, CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I-123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of uptake at caudate and putamen level was conducted through the BasGan software, also allowing partial volume effect correction. Because of the multicollinearity among neuropsychological tests and among SPECT variables, factor analysis was applied to 16 neuropsychological scores; moreover, the four SPECT variables were merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS factors: a dys-executive (NPS-EX), a visuospatial (NPS-VS), a verbal memory (NPS-VM), and a "mixed" (NPD-MIX) factor. In PD group, there were inverse correlations between UPDRS-III score and both NPS-VS (P < 0.01) and mSPECT (P < 0.05), and a direct correlation between mSPECT and NPS-EX (P < 0.05). Post hoc analysis showed a direct correlation between NPS-EX and caudate uptake in both hemispheres (P < 0.05). Moreover, inverse correlations were found between UPDRS-III and, respectively, putamen uptake in the less affected hemisphere (P < 0.01), and putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no correlation was found between mSPECT and either NPS or GDS values. Nigro-caudate function affects executive capabilities in PD but not in CTR, which appears to be unrelated to the disease motor severity at its onset. Instead, PD motor severity is related to nigro-putaminal impairment and visuospatial dysfunction. The role of these data as predictive features of cognitive decline and eventually dementia remains to be established in longitudinal studies.

Topics: Aged; Cognition Disorders; Corpus Striatum; Factor Analysis, Statistical; Female; Humans; Male; Middle Aged; Neural Pathways; Neuropsychological Tests; Parkinson Disease; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

The efficacy of dopamine (DA) agonists in the treatment of motor symptoms of Parkinson's disease (PD) has been clearly demonstrated. It has also been documented that DA agonists may have both a positive and a negative impact on neuropsychiatric symptoms in PD patients. This paper will focus on the effects of DA agonists on depressive and cognitive symptoms of PD.

Topics: Aged; Clinical Trials as Topic; Cognition Disorders; Depression; Dopamine Agonists; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Psychiatric Status Rating Scales; Radionuclide Imaging; Tropanes

Idiopathic rapid-eye-movement (REM) sleep behavior disorder (iRBD) has been suggested to be a risk factor for subsequent development of neurodegenerative disorders, especially Parkinson's disease (PD) and other alpha-synucleinopathies. At present, it is not possible to predict whether or not an iRBD patient will eventually develop PD. Here, we report 5 iRBD patients who underwent a test battery comprising a neurological examination (including UPDRS rating), mini mental state examination testing, transcranial sonography, olfactory function testing, and presynaptic dopamine transporter imaging with FP-CIT-SPECT. Our preliminary data show the diverse pattern of individual combinations of pathological findings when a multimodal assessment approach is applied in this patient group. Large-size longitudinal studies in iRBD patients are required to evaluate the usefulness of diagnostic tests to identify the subgroup of iRBD patients that is prone to develop PD.

Topics: Aged; Cognition Disorders; Humans; Male; Middle Aged; Neuropsychological Tests; Olfaction Disorders; Radiopharmaceuticals; REM Sleep Behavior Disorder; Severity of Illness Index; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes; Ultrasonography, Doppler, Transcranial