A Study of L-DOPA for Depression and Slowing in Older Adults

This study will elucidate the neurobiology of slowing and LLD, identify a novel therapeutic target for depression, and contribute to the development of personalized treatment regimens for LLD. The multimodal neuroimaging methods detailed in this application will provide information about the neurobiology of aging-associated slowing and LLD at molecular, structural, and functional levels of analysis. These data will fill a crucial gap in our knowledge regarding what are the physiologic and functional consequences of dopamine depletion occurring across the lifespan in individuals without PD. Results from this project also will allow us to evaluate a novel therapeutic approach to LLD, which could have large public health ramifications given the prevalence, frequent treatment resistance, and chronicity characteristic of LLD. Even apart from patients with LLD, cognitive and motor slowing exact a large public health burden in terms of impaired functioning and increased morbidity and mortality, and this burden will only grow as the population ages. It is critical to develop treatments capable of altering the negative health trajectories associated with slowing in order to help older adults maintain independent functioning and live longer with an increased quality of life. Finally, while PET and MRI may prove critical to understand the neurobiology of slowing and LLD, their invasiveness and expense limit their roles in informing treatment decisions in clinical practice settings. For this reason the investigators are also assessing the influence of genetic moderators such as interleukin-6 (IL-6) and catechol-O-methyl-transferase (COMT) genotype on baseline dopamine functioning and response to L-DOPA. This may facilitate the identification of both high-risk individuals and those most likely to benefit from treatment interventions.