Rodrigue KM, Kennedy KM, Devous Sr MD, Park DC.
Beta-amyloid in healthy aging: regional distribution and cognitive consequences.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Beta-amyloid deposition has been detected in vivo in a significant portion of non-demented older adults, but
the time course, regional distribution and cognitive consequences of this deposition is unclear. To address these
questions, we prospectively examined beta-amyloid across a lifespan sample of healthy adults and assessed
its impact on cognition. Participants (N = 137, aged 30-89) were scanned by PET using 18Florbetapir and were
administered a range of cognitive tests. Cognitive construct composites with two or more measures each were
calculated for speed of processing, working memory, reasoning, and crystallized intelligence. Standardized
uptake value ratios (SUVRs) were obtained from a priori masked regions of interest including anterior and posterior
cingulate, precuneus, lateral temporal, dorsolateral and orbital frontal, parietal, and occipital cortices. Our results
revealed a differential pattern of amyloid distribution across region and age. Some regions showed small, but
significant increases with aging, such as prefrontal and parietal cortices, whereas other regions displayed steeper
increases with age and greater variability in amyloid deposition in adults age 60 and over (e.g., anterior and posterior
cingulate, precuneus). These age-associated increases in amyloid burden were correlated with differences in
behavior. Specifically, across the entire sample increases in mean cortical amyloid burden were associated with
decreases in processing speed. Subanalysis of the group of older participants with the highest amyloid burden
showed stronger amyloid-cognitive associations. In the high-amyloid individuals, a dose-response effect was
observed where higher amyloid burden predicted poorer processing speed, working memory and fluid abilities.
Thus, beta-amyloid burden appears to first exert an effect on the most basic of cognitive measures (processing
speed), whereas higher-order cognitive operations such as working memory and fluid reasoning are only affected
in those with markedly elevated amyloid. Cognitive abilities which rely upon expertise, such as verbal abilities or
crystallized intelligence, are impervious to the effects of As deposition, at least in healthy adults.
Supported in part by NIH grants 5R37AG-006265-25, 3R37AG-006265-25S1, and Alzheimer's Association grant
IIRG-09-135087. Radiotracer was generously provided to the study by Avid Radiopharmaceuticals.