Pathways Linking Late-Life Depression to MCI & Dementia

The goal of this research study is to investigate the relationships among late-life depression (LLD), cognitive impairment and progressive neurodegeneration. The guiding hypothesis is that LLD patients have evolving cognitive impairments as a consequence of distinct underlying neuropathological changes, which frequently are expressed as Mild Cognitive Impairment (MCI). These neuropathological and cognitive changes are risk modifiers, lowering brain reserve capacity, and in turn, increasing risk of developing Alzheimer's Disease (AD). In order to pursue this goal we will enroll LLD, MCI, and normal control subjects to enrich our existing cohort to include a total of 150 elderly, non-demented, non-depressed subjects, 60 non-depressed MCI subjects and 270 LLD subjects. Using the joint infrastructure of the University of Pittsburgh's Advanced Center for Intervention and Services Research for Late-Life Mood Disorders and the Alzheimer's Disease Research Center, we will complete a detailed neurobehavioral evaluation, including clinical, neuropsychological, neuroimaging and biological markers, using these data to evaluate the factors associated with the development of MCI or dementia. Subjects will be studied annually for at least three years, allowing us to use longitudinal data to evaluate a series of linked hypotheses that postulate the pathways by which elderly, depressed patients develop cognitive impairment, and which may lead some to develop dementia.