It is well documented that older African Americans, on average, tend to perform more poorly on cognitive performance tests compared to age-matched Whites. Most research to date has been cross-sectional studies that focus on identifying factors that can account for their poorer performance. Because of the difficulty in accounting for cultural and educational biases associated with test measurement at a single point in time, these studies need to be complemented by examination of change in cognitive function. However, few studies have used a longitudinal design to examine risk factors for change in cognitive function over time in African Americans. One important risk factor that has gained increased attention is psychosocial stress and its relation to cognition and cognitive decline. A growing number of studies suggest that level of psychological distress, social isolation, and perceived stress are related to an increased rate of cognitive decline and dementia but the majority of the studies have only been conducted with older Whites. Older African Americans tend to be highly exposed to sources of chronic stress due to their disadvantaged position in US society, and report higher levels of some types of psychosocial stress, such as perceived discrimination and social isolation. The goal of the proposed project is to conduct an epidemiologic longitudinal study to examine the biological mechanisms that may account for the relation of psychosocial risk factors to cognitive decline that have been shown to be important in studies of older Whites, but have yet to be examined in older African Americans. The proposed study will capitalize on the risk factor data, longitudinal uniform structured clinical data, and detailed measures of cognitive abilities over time available on more than 350 older African Americans who are free of dementia at baseline and have agreed to annual clinical evaluations. In addition we will measure inflammatory markers in serum to test the hypothesis that psychosocial stress is related to cognitive decline in older African Americans, and this relation is mediated by inflammatory markers. The public health importance of identifying the mechanisms whereby psychosocial stress may be related to change in cognitive function is of critical importance and may increase the likelihood of early intervention strategies to prevent or slow cognitive decline in a rapidly growing minority population. The public health importance of understanding the ways in which chronic stress affects cognition in old age, as well as the underlying biologic mechanisms, is critical, particularly during a time of increased emphasis on early detection and intervention strategies to modify and ultimately prevent cognitive decline. [unreadable] [unreadable] [unreadable] [unreadable]