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

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 (18)F-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.

Figure 1. Age effects on β-amyloid (Aβ) deposition

(A) The effect of age on mean cortical uptake across the lifespan. Mean Aβ burden increases linearly from age 30 to 89 in healthy adults. The subgroup of individuals displayed in red showed elevated Aβ outside the 95% confidence interval of the sample. (B) Mean standardized uptake value ratio (SUVR) image of the elevated Aβ subgroup (n = 18, denoted in red in A). For comparison, (C) illustrates mean SUVR image in a group of 18 age- and sex-matched individuals with lower levels of amyloid.

Figure 2. Regional increases in β-amyloid deposition across the lifespan

The anterior cingulate, posterior cingulate, precuneus, and temporal cortices evidence the steepest increases in amyloid with age. Occipital, parietal, and prefrontal cortices evidence a shallower increase in amyloid deposition across the age range. SUVR = standardized uptake value ratio.

Figure 3. Effect of elevated β-amyloid (Aβ) deposition on 5 domains of cognition

Processing speed, working memory, and fluid reasoning are significantly reduced with increasing Aβ burden, whereas crystallized ability and episodic memory were unaffected.