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

The apolipoprotein E (APOE) e{open}4 allele and high levels of beta-amyloid (Aβ) are associated with episodic memory decline and risk for Alzheimer's disease. However, there is debate about independent or interactive effects of e{open}4 on Aβ-related memory decline in healthy older adults. Healthy older adults with high Aβ 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 Aβ+ e{open}4 noncarriers (n= 36), Aβ+ e{open}4 carriers (n= 48) showed significantly faster decline on memory tasks, which was by convention, moderate in magnitude (d= 0.40-0.47). Aβ positivity coupled with APOE e{open}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 Aβ is exacerbated by the presence of APOE e{open}4.