Individuals over 50 years of age comprise 11% of AIDS cases reported to the Centers for Disease Control and Prevention. A higher prevalence of AIDS in older individuals has been reported in certain states including Hawaii (20%) and Florida (13%). Although life expectancy in individuals with AIDS has increased with advances in antiretroviral therapy, it is likely that there are health consequences both of long-term infection and chronic antiretroviral therapy. Given the general increase in neurological disorders with age and the relatively high prevalence of cognitive dysfunction associated with HIV itself, the risk of HIV-associated dementia (HAD) in this aging HIV-seropositive subgroup is of particular concern. Existing data suggest, but have not conclusively demonstrated, increased rates of HAD in older compared with younger seropositive individuals. Preliminary data from the Hawaii Aging with HIV Cohort, a prospective cohort study designed to address this issue definitively, are presented. Factors underlying this hypothesized susceptibility in older individuals are discussed, including a synergy among HAD and other dementias, the role of vascular co-pathology, HIV and age-related immunological changes, and detrimental neuroglial changes that limit the compensatory ability of the aging brain.