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Abstract
Objective: Several lines of evidence suggest that pathologic changes underlying Alzheimer disease (AD) begin years prior to the clinical expression of the disease, underscoring the need for studies of cognitively healthy adults to capture these early changes. The overall goal of the current study was to map the cortical distribution of β-amyloid (Aβ) in a healthy adult lifespan sample (aged 30–89), and to assess the relationship between elevated amyloid and cognitive performance across multiple domains.
Methods: A total of 137 well-screened and cognitively normal adults underwent Aβ PET imaging with radiotracer 18F-florbetapir. Aβ load was estimated from 8 cortical regions. Participants were genotyped for APOE and tested for processing speed, working memory, fluid reasoning, episodic memory, and verbal ability.
Results: Aβ deposition is distributed differentially across the cortex and progresses at varying rates with age across cortical brain regions. A subset of cognitively normal adults aged 60 and over show markedly elevated deposition, and also had a higher rate of APOE ϵ4 (38%) than nonelevated adults (19%). Aβ burden was linked to poorer cognitive performance on measures of processing speed, working memory, and reasoning.
Conclusions: Even in a highly selected lifespan sample of adults, Aβ deposition is apparent in some adults and is influenced by APOE status. Greater amyloid burden was related to deleterious effects on cognition, suggesting that subtle cognitive changes accrue as amyloid progresses.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- DLBS=
- Dallas Lifespan Brain Study;
- DLPFC=
- dorsolateral prefrontal cortex;
- ETS=
- Educational Testing Service;
- FWHM=
- full width at half maximum;
- GLM=
- general linear model;
- MCI=
- mild cognitive impairment;
- OFC=
- orbital-frontal cortex;
- ROI=
- region of interest;
- SUVR=
- standardized uptake value ratio;
- WAIS=
- Wechsler Adult Intelligence Scale
Footnotes
Study funding: Supported by NIH grants 5R37AG-006265-25, 3R37AG-006265-25S1, and IIRG-09-135087 from the Alzheimer's Association. The ligand was provided to the study at no charge by Avid Radiopharmaceuticals, Inc.
Supplemental data at www.neurology.org
- Received May 23, 2011.
- Accepted September 29, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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