Impact of Amyloid Deposition on Neural and Cognitive Function in a Large Lifespan Sample of Healthy Adults

Beta-amyloid (Aß) is a key component of Alzheimer's disease pathology, and previous reports suggest that ∼25% of cognitively healthy older adults have increased levels of amyloid. Relatively little is known about the cognitive consequences of amyloid deposition in healthy adults, or the magnitude of its effects on cognition. In the present study, we examined the relationship of amyloid burden to cognitive function in a large lifespan sample of healthy adults, beginning at age 30 up to age 89. We hypothesized that amyloid would exert a negative effect on cognition, but expected that a substantial amount of age-related decline would remain, even after effects due to amyloid deposition were controlled. 137 highly educated (mean 16.40 years), healthy adults (age 30-89, mean MMSE 29.28) screened against history of cardiovascular, neurological or psychiatric conditions were scanned on a Siemens ECAT HR scanner 50 min after injection of 370 MBq bolus of 18F-AV-45(Florbetapir) to image beta-amyloid deposition. PET data were spatially normalized to an AV-45 template and SUVRs extracted from 8 ROIs (normalized to cerebellum). Two cognitive tests measured each of four domains: processing speed, working memory, fluid reasoning and crystallized intelligence. In the full sample (controlling forage), as amyloid burden increased, decreases were observed in processing speed, working memory, and fluid reasoning but not crystallized intelligence. A subgroup of 25 individuals aged 60+ with marked amyloid elevation (exceeded the 95% CI) showed strong associations between level of amyloid and cognitive function: in these subjects, higher amyloid burden was associated with decreased speed (r = -.59), working memory (r = -.63), and reasoning (r = -.54), but not crystallized ability. Despite these effects, when we removed these subjects from the sample, strong age-related decline was still observed in low amyloid participants.