Dataset Information

Brain Amyloid Deposition and Longitudinal Cognitive Decline in Nondemented Older Subjects: Results from a Multi-Ethnic Population.

ABSTRACT:

Objective

We aimed to whether the abnormally high amyloid-? (A?) level in the brain among apparently healthy elders is related with subtle cognitive deficits and/or accelerated cognitive decline.

Methods

A total of 116 dementia-free participants (mean age 84.5 years) of the Washington Heights Inwood Columbia Aging Project completed 18F-Florbetaben PET imaging. Positive or negative cerebral A? deposition was assessed visually. Quantitative cerebral A? burden was calculated as the standardized uptake value ratio in pre-established regions of interest using cerebellar cortex as the reference region. Cognition was determined using a neuropsychological battery and selected tests scores were combined into four composite scores (memory, language, executive/speed, and visuospatial) using exploratory factor analysis. We examined the relationship between cerebral A? level and longitudinal cognition change up to 20 years before the PET scan using latent growth curve models, controlling for age, education, ethnicity, and Apolipoprotein E (APOE) genotype.

Results

Positive reading of A? was found in 41 of 116 (35%) individuals. Cognitive scores at scan time was not related with A?. All cognitive scores declined over time. A? positive reading (B = -0.034, p = 0.02) and higher A? burden in temporal region (B = -0.080, p = 0.02) were associated with faster decline in executive/speed. Stratified analyses showed that higher A? deposition was associated with faster longitudinal declines in mean cognition, language, and executive/speed in African-Americans or in APOE ?4 carriers, and with faster memory decline in APOE ?4 carriers. The associations remained significant after excluding mild cognitive impairment participants.

Conclusions

High A? deposition in healthy elders was associated with decline in executive/speed in the decade before neuroimaging, and the association was observed primarily in African-Americans and APOE ?4 carriers. Our results suggest that measuring cerebral A? may give us important insights into the cognitive profile in the years prior to the scan in cognitively normal elders.

SUBMITTER: Gu Y

PROVIDER: S-EPMC4519341 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Brain Amyloid Deposition and Longitudinal Cognitive Decline in Nondemented Older Subjects: Results from a Multi-Ethnic Population.

Gu Yian Y Razlighi Qolamreza R QR Zahodne Laura B LB Janicki Sarah C SC Ichise Masanori M Manly Jennifer J JJ Devanand D P DP Brickman Adam M AM Schupf Nicole N Mayeux Richard R Stern Yaakov Y

PloS one 20150729 7

<h4>Objective</h4>We aimed to whether the abnormally high amyloid-β (Aβ) level in the brain among apparently healthy elders is related with subtle cognitive deficits and/or accelerated cognitive decline.<h4>Methods</h4>A total of 116 dementia-free participants (mean age 84.5 years) of the Washington Heights Inwood Columbia Aging Project completed 18F-Florbetaben PET imaging. Positive or negative cerebral Aβ deposition was assessed visually. Quantitative cerebral Aβ burden was calculated as the s ...[more]

PMID: 26221954

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Project description:ImportancePresently, the clinical standard for reporting the results of an amyloid positron emission tomography scan is to assign a dichotomous rating of positive or negative for the presence of amyloid. In a 4-year longitudinal study, we investigated whether using a continuous measure of the magnitude of baseline amyloid burden would provide valuable information about the rate of future cognitive decline over the subsequent 4 years compared with a dichotomous measure in middle-aged and older adults.ObjectiveTo examine whether a continuous, dose-response relationship between amyloid burden and cognitive decline was present among middle-aged and older adults.Design, setting, and participantsThis cohort study included 174 participants from the Dallas Lifespan Brain Study who were 40 to 89 years old at the beginning of the study, were cognitively normal at baseline (a Mini-Mental State Examination score of 26 or higher) with no history of neurological or psychiatric disorders, and had completed amyloid imaging ([18F]-florbetapir) at baseline and cognitive assessments at baseline and a 4-year follow-up. Continuous amyloid burden was measured as the mean cortical standardized uptake value ratio (SUVR) at baseline.Main outcomes and measuresLinear mixed models assessed the effect of increasing baseline amyloid over time (SUVR × time interaction) on episodic memory, reasoning, processing speed, vocabulary, and Mini-Mental State Examination performance. Age, sex, education, apolipoprotein ε4, and the random effect of intercepts were included as covariates.ResultsThe mean (SD) age for all participants (n = 174) was 66.44 (11.74) years, and 65 participants (37%) were men. The primary analyses yielded significant SUVR × time interactions in episodic memory, processing speed, vocabulary, and Mini-Mental State Examination performance, but not in reasoning performance. Higher baseline SUVR projected greater cognitive decline over 4 years. When controlling for variance related to a dichotomized positive/negative classification, most effects on cognition remained. Dichotomized amyloid status alone yielded fewer significant effects of amyloid on cognitive decline than continuous SUVR. Among amyloid-positive participants, increasing baseline SUVR predicted an increasing decline in episodic memory, but other effects on cognition were more limited. Finally, higher baseline amyloid burden among middle-aged adults was related to changes in vocabulary, with the effect driven by 3 apolipoprotein ε4 homozygotes.Conclusions and relevanceThese results suggest that the magnitude of amyloid burden at baseline is associated with the rate of cognitive decline over 4 years and potentially provides important information about the rate of future cognitive decline that is not available from a dichotomous positive/negative categorization.

Project description:The accumulation of beta amyloid in the brain has a complex and poorly understood impact on the progression of Parkinson's disease pathology and much controversy remains regarding its role, specifically in cognitive decline symptoms. Some studies have found increased beta amyloid burden is associated with worsening cognitive impairment in Parkinson's disease, especially in cases where dementia occurs, while other studies failed to replicate this finding. To better understand this relationship, we examined a cohort of 25 idiopathic Parkinson's disease patients and 30 healthy controls from the Parkinson's Progression Marker Initiative database. These participants underwent [18F]Florbetaben positron emission tomography scans to quantify beta amyloid deposition in 20 cortical regions. We then analyzed this beta amyloid data alongside the longitudinal Montreal Cognitive Assessment scores across 3 years to see how participant's baseline beta amyloid levels affected their cognitive scores prospectively. The first analysis we performed with these data was a hierarchical cluster analysis to help identify brain regions that shared similarity. We found that beta amyloid clusters differently in Parkinson's disease patients compared to healthy controls. In the Parkinson's disease group, increased beta amyloid burden in cluster 2 was associated with worse cognitive ability, compared to deposition in clusters 1 or 3. We also performed a stepwise linear regression where we found an adjusted R2 of 0.495 (49.5%) in a model explaining the Parkinson's disease group's Montreal Cognitive Assessment score 1-year post-scan, encompassing the left gyrus rectus, the left anterior cingulate cortex, and the right parietal cortex. Taken together, these results suggest regional beta amyloid deposition alone has a moderate effect on predicting future cognitive decline in Parkinson's disease patients. The patchwork effect of beta amyloid deposition on cognitive ability may be part of what separates cognitive impairment from cognitive sparing in Parkinson's disease. Thus, we suggest it would be more useful to measure beta amyloid burden in specific brain regions rather than using a whole-brain global beta amyloid composite score and use this information as a tool for determining which Parkinson's disease patients are most at risk for future cognitive decline.

Dataset Information

Brain Amyloid Deposition and Longitudinal Cognitive Decline in Nondemented Older Subjects: Results from a Multi-Ethnic Population.

Objective

Methods

Results

Conclusions

Publications

Brain Amyloid Deposition and Longitudinal Cognitive Decline in Nondemented Older Subjects: Results from a Multi-Ethnic Population.

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