Vascular factors, amyloid beta, and Alzheimer's disease

DESCRIPTION (provided by applicant): The applicant is a general internist with training in epidemiology that has worked in research of diabetes and Alzheimer's disease (AD) since 1999. The current proposal intends to expand the past experience of the applicant to the study of clinical cardiovascular risk factors and AD using novel approaches, including the use of plasma amyloid beta levels. The current proposal also intends to serve as a bridge to an independent investigator career in AD research through a period of mentored activities and the development of new skills necessary to become and independent investigator. The framework for this proposal is WHICAP, an ongoing cohort study of risk factors for dementia in a triethnic community of New York City funded by the NIA. The timetable for WHICAP coincides with the timetable of the K-08 award. This proposal will explore the associations between cardiovascular risk factors and AD through the examination of 5 hypotheses: 1) Clinical cardiovascular risk factors increase the likelihood of developing cognitive impairment without dementia and AD in susceptible individuals, defined by the presence of the APOE-g4 allele and high plasma concentrations of amyloid beta; 2)The presence of cerebrovascular disease and stroke precipitates the development of cognitive impairment without dementia and Alzheimer's disease in susceptible individuals defined by APOE-epsilon4 status and baseline concentrations of plasma amyloid beta. The presence of cerebrovascular disease and stroke increases the rate of change of amyloid beta plasma concentrations that is related to AD; 3) Differences in clinical cardiovascular risk factors, or of clusters of such factors, contribute to differences in the incidence of cognitive impairment without dementia and dementia among different ethnic groups; 4) if ethnic group differences in cardiovascular risk factors are associated with onset of Alzheimer's disease among ethnic groups, then cardiovascular risk factors should be associated with impairment in domains of the neuropsychological evaluation that are specific to Alzheimer's disease, such as delayed recall; 5) The differences observed in the incidence of cognitive deficit without dementia and Alzheimer's disease among ethnic groups and their association with cardiovascular risk factors are not explained by misclassification of cases of vascular dementia as cases of AD, and are associated with cases of dementia with high levels of plasma amyloid beta at baseline.