BRAIN STRUCTURAL COVARIANCE IN MIDLIFE: THE FRAMINGHAM OFFSPRING STUDY

from a sample of 266 healthy adults, aged 30-89 from the Dallas Lifespan Brain Study who received PETwith florbetapir. Eight bilateral ROIs were normalized to cerebellar hemispheres to estimate the mean cortical standardized uptake value ratio (SUVR). Twenty eight subjects with elevated amyloid were isolated using an iterative outlier method. Using GLM, age, education, lifetime cognition, and APOE 4 carrier status were used to predict mean cortical SUVR in separate samples of non-elevated middle aged adults 30-59 (n1⁄481), non-elevated older adults aged 60-89 (n1⁄4157) and all older adults including those with elevated amyloid (n1⁄4 176). Results:We found that age, APOE 4 status and lifestyle variables had the strongest effects on non-elevated amyloid in middle age. Most notably, higher age (p<.001) and low lifetime cognition in 4 carriers (p1⁄4.001) predicted higher SUVR in the middle-aged group. In older adults without elevated SUVR, only trend significant effects of lifetime cognition (p1⁄4.06) and a lifetime cognition x Education interaction (p1⁄4.056) were detected. If elevated SUVR subjects were included, age, APOE, education and lifetime cognition all interactively predicted SUVR, most notably with increasing amyloid across age for older adults with low but not high lifetime cognition (p<.001). Conclusions: Meaningful amounts of amyloid begin to accrue in middle-aged adults and accumulation is modified by both genetics and experiences, despite no evidence for accumulation at preclinical amyloid levels. These results suggest that amyloid systematically increases in vulnerable individuals beginning in young adulthood and that early experiences could modify accumulation and play a key role in delaying dementia onset.