Late-Life Depression (LLD), or depression in older adults, often presents with motivational
deficits, deficits in performance in cognitive domains including processing speed and
executive dysfunction, and mobility impairments. This triad of findings implicate
dopaminergic dysfunction as a core pathophysiologic feature in depression, and may contribute
to cognitive decline and motor disability. Normal aging results in brain-wide dopamine
declines, decreased D1/D2 receptor density, and loss of dopamine transporters. Although brain
changes associated with depression and aging converge on dopamine circuits, the specific
disturbances in LLD and how responsive the system is to modulation remain unclear. In this
collaborative study between Columbia University /New York State Psychiatric Institute and
Vanderbilt University Medical Center, investigators are testing integrative model that aging,
in concert with pro-inflammatory shifts, decreases dopamine signaling. These signally changes
affects behaviors supported by these circuits, in the context of age-associated cortical
atrophy and ischemic microvascular changes, resulting in variable LLD phenotypes.
Investigators propose a primary pathway where dopaminergic dysfunction in depressed elders
contributes to slowed processing speed and mobility impairments that increase the effort cost
associated with voluntary behavior. The central hypothesis of this study is that late-life
depression is characterized by dysfunction in the dopamine system and, by enhancing dopamine
functioning in the brain. By improving cognitive and motor slowing, administration of
carbidopa/levodopa (L-DOPA) will improve depressive symptoms.
Phase:
Phase 2
Details
Lead Sponsor:
Vanderbilt University Medical Center
Collaborators:
Columbia University Emory University
Treatments:
Carbidopa Carbidopa, levodopa drug combination Levodopa