The cross‐sectional association between APOE ε4 and cognition in midlife: Baseline data analysis of the Physical Activity and Alzheimer’s Disease study ‐ II

Abstract

AbstractBackgroundCarrying at least one ε4 allele of Apolipoprotein E (APOE ε4) is a strong genetic risk factor for cognitive decline in late life. However, how APOE ε4 is associated with cognition in midlife (to what extent and in which domains) remains unspecified. We investigated the association between APOE ε4 carrier status and various domains of memory and executive function in healthy, sedentary adults in midlife.MethodA subset of 91 participants (M age = 57±6 years; 86.8% females; 33 carriers and 58 non‐carriers of APOE ε4) from a larger study (PAAD‐II, NCT03876314) were included for analyses. At baseline, participants provided a passive drool saliva sample to determine APOE ε4 carrier status and completed a comprehensive cognitive assessment. Composite scores for auditory verbal learning, visuospatial memory, associative memory, story memory, mnemonic discrimination, working memory, inhibitory control, and fluid intelligence were computed. Analyses of covariance tested the effects of APOE ε4 on the composite scores with demographic factors as covariates.ResultSignificant effects of APOE ε4 on auditory verbal learning [F(1, 82) = 4.8, p<0.05] and fluid intelligence [F(1, 73) = 5.155, p<0.05] were found after controlling for the effects of age, race, education, and gender. APOE ε4 carriers’ z‐scores for auditory verbal learning (‐0.202±0.208) were lower than non‐carriers (0.164±0.104), and the same was found for fluid intelligence (carriers: ‐0.218±0.183; non‐carriers: 0.145±0.139). APOE ε4 was unrelated to other composite scores of memory and executive function (p’s>0.5).ConclusionEvidence from longitudinal studies suggests that negative effects of APOE ε4 on cognition are evident at 65–75 years old. We conducted a comprehensive assessment of multiple cognitive domains and demonstrated that APOE ε4 is negatively associated with some cognitive domains in midlife. These findings imply that, although APOE ε4 is a strong risk factor for cognitive decline in late life, its effects on cognitive aging could gradually start in midlife. The small but notable effects of APOE ε4 on comparably intact cognitive function in midlife suggests the potential importance of early preventive interventions (e.g., physical activity, healthy diet) for cognitive preservation in late life, especially in people with higher genetic risk for cognitive decline.