Neuropathology of Dementia in Centenarians

Many questions about the relationship between late-life aging and cognitive impairment are unanswered. It is not known which cognitive changes occur with age alone, and which are due to the presence of undiagnosed brain diseases, such as Alzheimer's disease (AD) and cerebral infarcts (CVAs). Among persons with the same degree of neuropathological burden, what factors will influence the clinical expression of dementia? This project will explore these questions by gathering clinical, cognitive and neuropathological data from a sample of centenarians (individuals 100 years old or older). The overall Program Project will identify and characterize a population-based, stratified sample of 242 centenarians from 31 northern Georgia counties. These subjects and their families will be asked to agree to brain donation after death. If they agree, they will be recruited into this project and will undergo standardized physical and cognitive examinations every 6 months thereafter until death. Then, following death, brain tissue will be removed and examined. Procedures for clinical, cognitive and neuropathological evaluations will conform to those currently being used in NIH funded research on other aging populations: the Nun Study and the Honolulu Asian Aging Study, adding to the diversity of subjects being studied with these methods. In particular, based upon the racial and ethnic characteristics of the north Georgia centenarian population, the Program Project (and consequently this project) is expected to enroll a high proportion of African-American subjects. Successful recruitment of African-Americans into this clinicopathological project would be especially valuable, as this ethnic group has been underrepresented in previous clinicopathological studies. The overall aim of this project is to explore relationships between senile plaque/neurofibrillary tangle counts, brain infarcts, functional abilities, cognitive measures, the presence of dementia and markers of neurocognitive reserves in a racially and educationally diverse sample of centenarians. Clinicopathological data will permit refinements of NIA-Reagan neuropathological criteria for AD in very elderly individuals.