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Regional brain amyloid-? accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

ABSTRACT: Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-? accumulation to these problems is unclear. We hypothesized that amyloid-? PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-? plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ?4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-? amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

SUBMITTER: Akhtar RS

PROVIDER: S-EPMC5444629 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

Akhtar Rizwan S RS Xie Sharon X SX Chen Yin J YJ Rick Jacqueline J Gross Rachel G RG Nasrallah Ilya M IM Van Deerlin Vivianna M VM Trojanowski John Q JQ Chen-Plotkin Alice S AS Hurtig Howard I HI Siderowf Andrew D AD Dubroff Jacob G JG Weintraub Daniel D

PloS one 20170525 5

Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in indi ...[more]

PMID: 28542444

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Project description:Importance:Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. Objective:To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia. Design, Setting, and Participants:This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017. Main Outcomes and Measures:Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype. Results:Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years. Conclusions and Relevance:Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.

Project description:Importance:Aging is associated with excessive daytime sleepiness (EDS), which has been linked to cognitive decline in the elderly. However, whether EDS is associated with the pathologic processes of Alzheimer disease remains unclear. Objective:To investigate whether EDS at baseline is associated with a longitudinal increase in regional β-amyloid (Aβ) accumulation in a cohort of elderly individuals without dementia. Design, Setting, and Participants:This prospective analysis included participants enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study in Olmsted County, Minnesota. Of 2900 participants, 2172 (74.9%) agreed to undergo carbon 11-labeled Pittsburgh compound B positron emission tomography (PiB-PET). We included 283 participants 70 years or older without dementia who completed surveys assessing sleepiness at baseline and had at least 2 consecutive PiB-PET scans from January 1, 2009, through July 31, 2016, after excluding 45 (13.7%) who had a comorbid neurologic disorder. Main Outcomes and Measures:Excessive daytime sleepiness was defined as an Epworth Sleepiness Scale score of at least 10. The difference in Aβ levels between the 2 consecutive scans (ΔPiB) in Aβ-susceptible regions (prefrontal, anterior cingulate, posterior cingulate-precuneus, and parietal) was determined. Multiple linear regression models were fit to explore associations between baseline EDS and ΔPiB while adjusting for baseline age, sex, presence of the apolipoprotein E ε4 allele, educational level, baseline PiB uptake, global PiB positivity (standardized uptake value ratio ≥1.4), physical activity, cardiovascular comorbidities (obesity, hypertension, hyperlipidemia, and diabetes), reduced sleep duration, respiratory symptoms during sleep, depression, and interval between scans. Results:Of the initial 283 participants, mean (SD) age was 77.1 (4.8) years; 204 (72.1%) were men and 79 (27.9%) were women. Sixty-three participants (22.3%) had EDS. Baseline EDS was significantly associated with increased regional Aβ accumulation in the anterior cingulate (B coefficient = 0.031; 95% CI, 0.001-0.061; P = .04), posterior cingulate-precuneus (B coefficient = 0.038; 95% CI, 0.006-0.069; P = .02), and parietal (B coefficient = 0.033; 95% CI, 0.001-0.065; P = .04) regions. Association of EDS with longitudinal Aβ accumulation was stronger in participants with baseline global PiB positivity in the anterior cingulate (B coefficient = 0.065; 95% CI, 0.010-0.118; P = .02) and cingulate-precuneus (B coefficient = 0.068; 95% CI, 0.009-0.126; P = .02) regions. Conclusions and Relevance:Baseline EDS was associated with increased longitudinal Aβ accumulation in elderly persons without dementia, suggesting that those with EDS may be more vulnerable to pathologic changes associated with Alzheimer disease. Further work is needed to elucidate whether EDS is a clinical marker of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers. Early identification of patients with EDS and treatment of underlying sleep disorders could reduce Aβ accumulation in this vulnerable group.

Dataset Information

Regional brain amyloid-? accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

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Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

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