This proposal uses the K23 mechanism, Mentored Patient-Oriented Research Career Development Award. The applicant is a geriatric neurologist and Assistant Research Professor of Psychiatry at Duke University who proposes to develop the skills necessary to bridge clinical research in geriatric psychiatry with cognitive neuroscience. Career development activities will focus on clinical research of geriatric psychiatry and functional MRI. The emphasis of the training will be on neuropsychological assessment and on the challenges of conducting longitudinal fMRI studies with psychiatrically ill elderly and interpreting their findings. Skills will be applied to research in late-life depression (LLD), which will be conducted under the sponsorship of the Department of Psychiatry, Duke Conte Center and Duke-UNC Brain Imaging and Analysis Center (BIAC). LLD increases risk for development of persistent cognitive impairment (Cl). Early identification of patients with cognitive decline is critical for clinical intervention to slow down the disease progression. The applicant will conduct an fMRI follow-up study to investigate the feasibility of using fMRI to predict the development of Cl in LLD. Initial efforts will focus on identifying functional abnormalities in the dorsal attention-executive system (e.g., dorsolateral prefrontal cortex and dorsal anterior cingulate cortex) and ventral emotional system (e.g., ventromedial prefrontal cortex, lateral orbital frontal cortex, and amygdala) in LLD patients with Cl. The first phase will test the hypotheses about cognitive and emotional dysfunction in these regions in LLD patients with Cl relative to healthy controls. The second phase will focus on the re-imaging of controls and patients one year later to identify individuals with cognitive decline. The association of brain activation and neuropsychological performance in the first entry will be used to predict cognitive decline in one year later. The sensitivity and specificity of fMRI in predicting cognitive decline will be examined. The impact of the one-year longitudinal outcomes of depression measured by Montgomery- Asberg Depression Rating Scale (MADRS) on the function of working memory and emotional processing measured in by fMRI will also be examined. The proposal will not only help early diagnosis and clinical intervention of Cl, but also will deepen our knowledge of the neural substrates associated with executive and emotional function in the elderly.
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