The Separate and Interactive Effects of HIV and APOE Genotype on Cognition among Women

Women with HIV are vulnerable to cognitive dysfunction compared to male counterparts. Genetic factors have not been widely examined as a contributor to cognitive dysfunction in HIV+ women. The goal of this study was to examine cognitive function in relation to Apolipoprotein E (APOE) genotype in HIV+ and HIV- women. A total of 714 women from the Women’s Interagency HIV Study (WIHS) (68.9% HIV+, 32.9% ε4+) had both longitudinal cognitive data over three visits and APOE genotyping available for analysis. We found there was no main effect of APOE genotype on any cognitive domain. We found a significant interactive effect of HIV, APOE and time on global cognition, driven by small negative effects of the APOE ε4 allele in the HIV- control group. Finally, we found that in HIV+ women, there was a significant interactive effect between APOE and age on executive functioning, global cognition, motor skills, and processing speed, such that older HIV+ ε4+ women performed worse than older HIV+ ε4- women. In contrast, there was no main effect of APOE ε4 carrier status on any cognitive domain in younger HIV+ women or either age group of HIV- controls. Overall, the current findings suggest that APOE genotype may be an age-related risk factor for cognitive dysfunction in HIV+ women.