Mentoring to Develop Aging-Informed Patient-Oriented Research in Neuropsychiatry

The rising public health burden attributable to brain-based conditions of aging such as cognitive decline/dementia and depression requires more clinicians to provide care and more patient oriented researchers to develop novel therapeutics. Moreover, effectively treating the rising numbers of older adults with diverse mental disorders not traditionally associated with aging (e.g., Posttraumatic Stress Disorder, Schizophrenia, etc.) requires an understanding of how these disorders interact with later life development and common geriatric syndromes. Yet, in the face of this daunting challenge, ACGME-accredited geriatric psychiatry programs nationwide declined by 18% over the past 20 years, and the number of filled positions declined by 46.6%. There continue to be too few clinical and basic researchers focused on neuropsychiatric disorders in later life and insufficient numbers of investigators possessing specific training in the complexities unique to late-life disorders. To help address these gaps, the goal of this K24 Midcareer Award application is to provide mentoring that will increase the pipeline of junior investigators possessing the motivation and expertise to conduct patient-oriented research on neuropsychiatric disorders in older adults. The proposed mentoring plan integrates complementary strategies to (1) facilitate the development (both at Columbia and beyond) of clinician-scientists committed to a career in later life neuropsychiatric research and (2) provide a broader population of (non-geriatric identified) investigators pursuing research across a range of mental disorders with an increased knowledge of aging and geroscience. Additionally, a coordinated plan of training activities will increase the Candidate?s expertise in the cognitive neuroscience of dopaminergic brain circuits, the assessment and determinants of mobility, and the design of research studies including exercise. The innovative new research proposed exemplifies the transdisciplinary, aging-informed research to be fostered during this Award and will provide diverse additional opportunities for mentees. N=80 adults aged > 60 years with a significant depressive disorder and slowed processing and/or gait speed will be randomized to receive levodopa (L-DOPA; which the Candidate has previously shown to increase psychomotor speed and decrease depressive symptoms in older adults), aerobic exercise (itself an effective antidepressant treatment as monotherapy), or their combination in a 2x2 design incorporating placebo and a stretching/toning control. Participants will be evaluated before and after this 12-week duration study across cognitive domains, psychiatric symptoms, gait kinematics and mobility, and task-based magnetic resonance imaging (MRI) focused on effort-based decision making and reward processing. Thus, the training, mentoring, and research activities proposed in this K24 Award will contribute toward the development of improved treatment and prevention strategies to maximize the functioning and active healthspan of older adults with neuropsychiatric disorders.