Background: Increasing evidence indicates that lifestyle factors such as high levels of education and lifetime cognitive activity predict lower levels of amyloid deposition in healthy older adults, suggesting these experiences may confer protection against accumulation. Little is known, however about amyloid in young and middle age. We assessed whether there were reliable increases in amyloid deposition in 266 healthy adults from 30 to 89, and primarily focused on identifying variables that predicted amyloid accumulation in those aged 30 to 59.
      Methods: Data were analyzed from a sample of 266 healthy adults, aged 30-89 from the Dallas Lifespan Brain Study who received PET with 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 Ɛ4 carrier status were used to predict mean cortical SUVR in separate samples of non-elevated middle aged adults 30-59 (n=81), non-elevated older adults aged 60-89 (n=157) and all older adults including those with elevated amyloid (n = 176).
      Results: We found that age, APOE Ɛ4 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 Ɛ4 carriers (p=.001) predicted higher SUVR in the middle-aged group. In older adults without elevated SUVR, only trend significant effects of lifetime cognition (p=.06) and a lifetime cognition x Education interaction (p=.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.