George S Alexopoulos   Professor of Psychiatry

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Biology of Late Life Depression

George Alexopoulos, M.D. is the founder and Director of the Weill-Cornell Institute of Geriatric Psychiatry a Professor of Psychiatry and the Director of the NIMH-supported (P30) Advanced Center for Interventions and Services Research (ACISR) in Late-Life Depression. His research has been guided by the hypothesis that geriatric depression is a heterogeneous entity that includes patients in whom aging-related processes and neurological brain diseases modify the course of illness and the effects of treatment. Through a series of cross-sectional studies, Dr. Alexopoulos and his colleagues observed that late-onset depressives have a higher prevalence of dementia than elderly depressed patients with onset onset of first episode in early life. When not demented, late-onset depressives appear to have stigmata of neurological dementing disorders, including cognitive dysfunction and structural brain abnormalities. His lab has previously characterized the heterogeneity of geriatric depression, tested its response to acute pharmacological treatment, and described its course under naturalistic conditions. In recent studies he has sought to identify the timetable and predictors of recovery in elderly patients with major depression and to investigate the relationship of disability to clinical parameters that are part of a comprehensive psychiatric examination. Dr. Alexopoulos and his coworkers identified and defined distinct stages of geriatric depression, e.g., period from onset to recovery, period preceding recovery, or period preceding relapse, etc. Using survival analysis, growth curve analysis, and other analytic methods, Dr. Alexopoulos is now studying clinical and neuropsychological features as well as microstructural and processing brain abnormalities predicting poor short-term and long-term outcomes of late life depression. This approach allowed further dissection of the geriatric depression syndrome based on the course of illness and its relationship to meaningful clinical and biological characteristics. He identified syndromes such as the "depression-executive dysfunction of late life" and "vascular depression". These syndromes have rather distinct clinical presentation, and a poor response to conventional antidepressant treatments. However, they may respond or be prevented by novel pharmacological and non-pharmacological approaches. These findings are expected to guide geriatric antidepressant treatment practice and provide the background for sharply focused investigations of the mechanisms of specific geriatric depressive syndromes. Dr. Alexopoulos' current work focuses on the "effectiveness" of conventional and novel therapies when offered in community settings and on the dissemination of evidence-based practices.


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  • Weill Cornell Medical College, Cornell University