Amyloid and APOE epsilon 4 interact to influence short-term decline in preclinical Alzheimer disease

Objective:To examine whether -amyloid (A) and APOE epsilon 4 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN).Methods:Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the contributions of APOE epsilon 4 and A on longitudinal change over a median of 1.49 years were examined. Cognitive decline was assessed with the Mini-Mental State Examination (MMSE) and Logical Memory (immediate and delayed recall scores).Results:High A participants were more likely to be APOE epsilon 4+ than low A participants. CNs who were both high A and APOE epsilon 4+ showed greater decline in Logical Memory immediate recall (p <0.087), Logical Memory delayed recall (p <0.024), and MMSE (p <0.034) compared to all other groups (low A/APOE epsilon 4-, low A/APOE epsilon 4+, and high A/APOE epsilon 4-). No other pairwise contrast was significant for any cognitive measure.Conclusions:Clinically normal individuals who are APOE epsilon 4+ and have high A showed the highest cognitive decline. These results suggest that A and APOE epsilon 4 are not redundant contributors of decline in aging but rather interact to promote decline during the short follow-up period examined in this study. Longer follow-up periods will be essential to fully elucidate the influence of Alzheimer disease risk factors on cognitive decline in aging.