THE ASSOCIATION BETWEEN APOE ε4 AND AGE-RELATED RESTING STATE FUNCTIONAL CONNECTIVITY IN A COMMUNITY-BASED SAMPLE OF RACIALLY/ETHNICALLY DIVERSE OLDER ADULTS

Abstract

Several studies have reported age-related alterations in resting-state functional connectivity of the default mode network (DMN), but we lack an understanding of the mechanisms underlying these functional changes. Further, epidemiological and genome-wide association studies suggest that Alzheimer's disease (AD) may manifest differently according to race and susceptibility genes. For example, Apolipoprotein E (APOE) ε4 is a known risk factor of AD, but notably, the relationship between APOE e4 and AD differs across race and ethnicity. No study to date has examined whether race/ethnicity and APOE status moderate the relationship between age and DMN connectivity. We determined whether APOE status moderates the relationship between age and DMN connectivity in a community-based sample of racially/ethnically diverse older adults from the Washington Heights-Inwood Community Aging Project (WHICAP) study. Participants were 383 non-demented (35% White, 34% Black, 31% Hispanic; M age=74yrs SD=6; 56% women) older adults in a longitudinal aging study, who underwent a neuropsychological evaluation and 3T MRI scanning. We used linear regression models with intra-network connectivity between midline (hippocampus) and posterior (posterior cingulate) nodes of the DMN as dependent variables. Age, APOE status (ε4 present or absent), race/ethnicity, and the interaction between APOE status and age were independent variables; the models adjusted for sex/gender and recruitment cohort. Increased age was associated with reduced functional connectivity (main effect of age, β=−.001, [−.006, .003]). APOE ε4+ participants showed greater age-related decline in DMN connectivity (APOE and age interaction, β=−.010,[−.017,−.002]) . Stratified by race/ethnicity this effect was largest in Hispanics (β=−.018,[−.036,0]), compared with Blacks (β=−.011,[−.025,.003]), and Whites (β=−.010,[−.024,.004]). APOE status moderated age-related differences in resting state functional connectivity. Nevertheless, this relationship was similar across race/ethnicity. Future analyses will examine age-related changes in other modalities of brain health (e.g., white matter integrity, grey matter volume, cortical thickness) to investigate the role of APOE in racially/ethnically diverse older adults.