Dopaminergic Dysfunction in Late-Life Depression

Summary

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 study, 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.

Conditions

• Late Life Depression
• Cognitive Decline
• Depressive Disorder, Treatment-Resistant
• Levodopa
• Gait Impairment

Interventions

DRUG

L-Dopa

Generic 25/100mg carbidopa/levodopa (Sinemet)capsules will be administered in this study. Participants will begin randomized double blinded 3- week trial of Levodopa. Dose titration starting at 150 mg /daily to maximum of 450 mg daily three times a day for three weeks. After one week of taper participants will enter step 2 phase of study where carbidopa/levodopa matched placebo will be administered for 3 weeks afterwards dose will be slowly tapered over next 7 days.

DRUG

Placebo

Step 1 (3 weeks) Carbidopa/levodopa-matched placebo capsules 3 times. Followed by 1 week of taper. Step2(3 weeks):150-450mg carbidopa/levodopa 3 times daily for three weeks .Followed by 1 week of taper.

Sponsors & Collaborators

• Emory University

  collaborator OTHER

• University of Pittsburgh

  collaborator OTHER

• University of Pittsburgh Medical Center

  collaborator OTHER

• Rutgers University

  collaborator OTHER

• University of North Carolina, Chapel Hill

  collaborator OTHER

• Vanderbilt University Medical Center

  lead OTHER

Principal Investigators

• Warren Taylor, MD,MHSc · Vanderbilt University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-02-15

Primary Completion

2026-04-30

Completion

2026-07-30

FDA Drug

Yes

Countries

• United States

Study Locations