APOE ε4 moderates amyloid-related memory decline in preclinical Alzheimer's disease

The apolipoprotein E (APOE) epsilon 4 allele and high levels of beta-amyloid (A beta) are associated with episodic memory decline and risk for Alzheimer's disease. However, there is debate about independent or interactive effects of epsilon 4 on A beta-related memory decline in healthy older adults. Healthy older adults with high A beta burden (n = 84) enrolled in Australian Imaging, Biomarkers, and Lifestyle Study were included in this study. Cognition was measured using the computerized Cogstate Brief Battery at baseline, 18-, 36-, and 54-month follow-ups. Mini Mental State Examination and Clinical Dementia Rating scales were also administered at baseline and each follow-up timepoint. Relative to A beta + epsilon 4 noncarriers (n - 36), A beta + epsilon 4 carriers (n = 48) showed significantly faster decline on memory tasks, which was by convention, moderate in magnitude (d = 0.40-0.47). A beta positivity coupled with APOE epsilon 4 was associated with moderately increased decline in memory over a 54-month assessment period, suggesting that, in the preclinical stages of Alzheimer's disease, the manifestation of memory decline in older adults with high A beta is exacerbated by the presence of APOE epsilon 4. (C) 2015 Elsevier Inc. All rights reserved.