Preclinical detection of an illness, such as Alzheimer's disease (AD), by the presence of specific risk factors and biomarkers and a typical trajectory of cognitive decline, may allow a much earlier diagnosis, thus permitting therapeutic intervention before symptoms are firmly established. In this proposal, we will study declines in specific cognitive domains in 400 older individuals with normal cognitive function and 300 patients newly diagnosed with MCI. About 40% of subjects will be Hispanic, and we will evaluate whether specific demographic, psychological and medical risk factors associated with this ethnicity have an impact on the trajectory of cognitive decline. Our objectives are: (1) to determine how specific biomarkers and risk factors for degenerative diseasess, such as AD and cerebrovascular disease, are associated with baseline levels and slopes of trajectories of cognitive declines in cognitively normal individuals and those diagnosed with MCI; (2) to determine the association of measures of reserve, including attained education and intracranial volume, with the same decline measures; and (3) to compare the rates of progression to a diagnosis of probable AD among subjects diagnosed to have prodromal AD (MCI-AD) versus prodromal non-AD dementia (MCl-non-AD). Growth mixture model analysis and Cox proportional hazard regression will be used. We hypothesize that the baseline level (intercept) and rate of cognitive decline (slope) in normal elderly and MCI patients will be related to biomarkers for Alzheimer and vascular neuropathology, and that brain (cognitive) reserve will be associated with the intercept, but not the slope of these trajectories. We also hypothesize that subjects with a diagnosis of either MCI-AD or amnestic or multi-domain MCI will have more rapid rates of progression to a diagnosis of probable AD than those with other diagnoses. Subjects will be recruited and followed annually by the Clinical Core, using uniform diagnostic and assessment procedures at the two clinical research centers in Miami and Tampa.
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