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Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings.

ABSTRACT: The Parkinson Associated Risk Syndrome Study identified a cohort of healthy adults with hyposmia and dopamine transporter binding reduction to characterize individuals at risk for Parkinson's disease (PD). We describe the cognitive profile of this cohort.Individuals older than 50 y without PD were recruited. Two hundred twenty-five completed cognitive testing and were included in the final analysis. A neuropsychological test battery was administered and normative scores created for global cognition, memory, executive function/working memory, processing speed/attention, visuospatial abilities, and language domains. Other non-motor symptoms (constipation, depression, anxiety, and rapid eye movement sleep behavior disorder) were assessed through questionnaires.Individuals with both hyposmia and reduced dopamine transporter binding (n?=?38) had lower mean scores for global cognition, executive function/working memory, and memory compared with all other participants (n?=?187). In separate multivariate logistic regression models, lower global cognition (odds ratio, 1.97, P?=?0.004), and specifically executive function/working memory (odds ratio, 1.84, P?=?0.004) scores were associated with membership in the hyposmia with dopamine transporter reduction group. Combining hyposmia with relative impairment on specific cognitive domains increased the odds of dopamine transporter binding reduction compared with hyposmia alone, with the greatest increase in odds for hyposmia plus executive function/working memory relative impairment (68% increase in odds from 4.14 to 6.96).Changes in global cognitive abilities, and specifically executive function/working memory, are present in individuals at risk for PD. Combining non-motor features, including cognition, improves prediction of dopamine transporter binding reduction.

SUBMITTER: Chahine LM

PROVIDER: S-EPMC4827252 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings.

Chahine Lama M LM Weintraub Daniel D Hawkins Keith A KA Siderowf Andrew A Eberly Shirley S Oakes David D Seibyl John J Stern Matthew B MB Marek Kenneth K Jennings Danna D

Movement disorders : official journal of the Movement Disorder Society 20150821 1

<h4>Objectives</h4>The Parkinson Associated Risk Syndrome Study identified a cohort of healthy adults with hyposmia and dopamine transporter binding reduction to characterize individuals at risk for Parkinson's disease (PD). We describe the cognitive profile of this cohort.<h4>Methods</h4>Individuals older than 50 y without PD were recruited. Two hundred twenty-five completed cognitive testing and were included in the final analysis. A neuropsychological test battery was administered and normati ...[more]

PMID: 26293177

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Project description:ObjectiveSerotoninergic neurotransmission may modulate β-amyloid peptide (Aβ) metabolism through upregulation of α-secretase. Early Parkinson disease (PD) shows variable serotoninergic denervation, which may impact Aβ deposition.MethodsWe conducted 3 analyses to explore associations between serotoninergic neurotransmission and cerebral Aβ burden in PD. The first was a cross-sectional imaging study of PD subjects (n = 23) using the serotoninergic transporter positron emission tomography (PET) ligand [11 C]3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile (DASB) and amyloid PET Pittsburgh compound B ([11 C]PiB). The second was a baseline study of Parkinson's Progression Markers Initiative (PPMI) subjects exploring the influence of serotoninergic medications on cerebrospinal fluid (CSF) Aβ-42 levels (n = 389), controlling for age, sex, Geriatric Depression Scale, disease duration, and education. Third, we fit an interval censored proportional hazard model with longitudinal PPMI data (n = 367) to test whether serotoninergic medication use associates with reduced risk of PD cognitive decline, defined as time to reach a Montreal Cognitive Assessment score ≤ 20, adjusting for baseline caudate dopamine transporter [123 I]ioflupane single photon emission computed tomography and CSF Aβ-42 levels.ResultsSerotoninergic DASB distribution volume ratio (DVR) inversely associated with PiB DVR in the cerebral cortex (Pearson r = -0.478, p = 0.021) but not the striatum (r = -0.264, p = 0.224). In the baseline PPMI analysis, serotoninergic medication use for ≥6 months associated with a lower level of CSF Aβ-42 (t = -2.20, p = 0.029). In the longitudinal PPMI model, baseline serotoninergic medication use associated with a reduced risk of cognitive decline (t = -2.03, p = 0.043) after controlling for covariates.InterpretationCortical Aβ burden in PD associates inversely with serotoninergic innervation. Serotoninergic medications may alter Aβ metabolism and reduce the risk of PD cognitive decline. Ann Neurol 2018;83:994-1002.

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Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings.

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Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings.

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