This is an application for a Mentored Patient-Oriented Research Career Development Award. From epidemiological studies we know that depressive and cognitive disorders frequently co-exist in elderly patients. Recent data suggest that the presence of depression (DEP) increases the risk of dementia in patients with mild cognitive impairment (MCI). This MPRCDA application requests support for a career development and research plan to study the interface between depression and cognitive impairment. The research plan grew from an open treatment, pilot study, using the antidepressant sertraline in elderly patients with concurrent DEP-MCI (without dementia). The intent-to-treat response rate was 50% (16/32), completers response rate 73% (16/22), and responders showed mixed improvement in cognition. In the research plan, the candidate will: i) Obtain a baseline psychiatric and neuropsychological test profile, and a baseline MRI in 100 DEP-MCI patients, looking at severity of encephalomalacia and cortical atrophy; ii) conduct a double-blind, placebo-controlled clinical trial, examining the antidepressant response rate and side effect profile of an SSRI (sertraline); iii) Determine if cognitive change on neuropsychological tests improves after successful antidepressant treatment; iv) Assess the quality of life after antidepressant treatment; v) In a naturalistic, 3-year follow-up, evaluate the risk of developing dementia. This application provides an excellent training structure for the candidate while addressing clinically relevant questions. Critically, the career development activities build on the candidate's background in psychiatry and research and capitalize on the resources of Columbia University to permit him to achieve the long term goal to become an independent investigator addressing the interface of depression and cognitive impairment in the elderly from both a treatment and pathophysiological perspective. In the linked training plan, the candidate will A) Participate in a comprehensive didactic program, including course work in: i) research design and quantitative methods, ii) structural neuroimaging (MRI), iii) neuropsychological testing methodology and interpretation, and iv) clinical trials and the ethical conduct of research. B) Obtain expert guidance and mentorship in key areas, including: i) subtleties of clinical assessment and diagnosis, ii) application of feasible research designs and appropriate quantitative methods, iii) MRI methodology and interpretation, iv) neuropsychological test performance patterns in elderly normals, MCI and dementia, examining the role of postulated confounds like depression, and v) subtleties of clinical trials and ethical conduct of research.
