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

High levels of beta-amyloid (A beta) in the brain and carriage of the APOE epsilon 4 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 A beta level, APOE epsilon 4 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 A beta who were also APOE epsilon 4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE epsilon 4 non-carriers, high A beta was unrelated to cognitive decline in learning and working memory. Carriage of APOE epsilon 4 in CN older adults with low A beta 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 A beta and APOE epsilon 4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of A beta and APOE epsilon 4 as biomarkers of early Alzheimer's disease.