Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months.

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE e4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE e4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE e4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE e4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE e4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE e4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE e4 as biomarkers of early Alzheimer’s disease.