ß-Amyloid burden in healthy aging: regional distribution and cognitive consequences.

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 ß-amyloid (Aß) 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 Aß PET imaging with radiotracer (18)F-florbetapir. Aß 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: Aß 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%). Aß 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, Aß 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.

Differential aging of the medial temporal lobe: a study of a five-year change.

OBJECTIVE: To test the hypothesis that entorhinal cortex (EC) volume decreases at a slower rate than the hippocampal (HC) volume in healthy adults, and to examine whether the rate of shrinkage increases with age. METHODS: Volumes of the HC and EC were measured twice on MRI scans of 54 healthy adults (aged 26 to 82 years), with an average interval of 5 years. RESULTS: Markedly different age trends were noted in the examined regions. The EC showed no age-related differences on both occasions and only minimal age-related change (0.33%/y). By contrast, the HC exhibited significant age-related differences at baseline and at follow-up evaluation and decreased at a faster pace of 0.86%/y. Older participants (aged > or = 50 years) showed increased annual shrinkage of the HC (1.18%) and EC shrinkage (0.53%/y). The rate of HC volume loss significantly exceeded that of the EC. No EC shrinkage and modest HC volume reduction were observed in people aged <50 years. CONCLUSIONS: Age-related shrinkage occurs in the medial temporal lobes of healthy adults, with significant hippocampal decline and minimal entorhinal changes. In both regions, the rate of decline accelerates with age, although the role of pathologic factors in age-related increase of volume loss merits further investigation.