Cardiovascular risk factors and APOE‐ε4 status affect memory functioning in aging via changes to temporal stem diffusion

Abstract

Prior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age-related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE-ε4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion-weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE-ε4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.