Cognitive Enhancement in Depression (The COG-D Study)

Non-invasive Neuromodulation to Enhance Targeted Cognitive Remediation in Older Adults With Depression

This study will investigate whether transcranial direct current stimulation (tDCS) enhances the effects of computerized cognitive training in older adults with recurrent depression (2 or more lifetime episodes; either current or within past 3 years).

Study Overview

• Status: Completed
• Conditions: Depression; Aging; Cognitive Symptom
• Intervention / Treatment: Behavioral: Cognitive Training; Device: tDCS (active stimulation); Device: tDCS (sham stimulation)

Detailed Description

The purpose of this study is to determine whether the addition of active tDCS to computerized cognitive remediation (nCCR) enhances brain activity and cognitive functions in older adults with recurrent depression to a greater degree than nCCR with sham stimulation. The investigators will randomize 20 elderly depressed outpatients to either double-blinded active or sham bifrontal tDCS plus daily nCCR over 4-weeks. Multimodal MRI (focused on the cognitive control network; CCN) and psychiatric and neuropsychological evaluations will be obtained at baseline and following intervention completion. Long-term CCN cognitive effects will be explored 3-months post-intervention via cognitive assessments.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 60+ years
• Diagnosis of a current or past (within last 3 years) depressive episode (e.g., Major Depressive Disorder (MDD), Persistent Depressive Disorder (PDD)) using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria
• In total, participants must have 2 or more lifetime depressive episodes to be considered "recurrent"
• Either stable antidepressant regimen for at least 6 weeks or no current antidepressant treatment
• Evidence of subjective cognitive complaints on the Everyday Cognition Scale (ECog)
• English fluency

Exclusion criteria:

• Other Axis I psychiatric conditions via the DSM-5, except for anxiety symptoms occurring in a depressive episode
• Acute suicidality on clinical evaluation
• Acute grief
• History of alcohol use disorder or substance use disorder in last 12 months
• Currently taking medications that would significantly interact with tDCS effects (such as sodium channel blockers or anticonvulsants)
• Neurological disorders (e.g., dementia, stroke, seizures, traumatic brain injury, Parkinson's disease)
• Montreal Cognitive Assessment (MoCA) score < 23
• Primary amnestic cognitive profile (>1.5 standard deviations (SDs) below demographically-adjusted mean on National Alzheimer's Coordinating Center (NACC) memory measures in context of otherwise normal cognitive profile)
• Any physical or intellectual disability affecting ability to complete assessments
• Unstable medical illness needing urgent treatment
• MRI contraindications
• Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) in last 2 months
• Current involvement in psychotherapy
• Current involvement in other research studies (including but not limited to: neuromodulation [TMS or tDCS] or investigational drug studies)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive Training + Active Stimulation; This arm receives cognitive training combined with active tDCS.	Behavioral: Cognitive Training; Computerized cognitive training targeting the underlying cerebral networks associated with depression.; Device: tDCS (active stimulation); A Soterix Clinical Trials Direct Current Stimulator will apply 20 minutes of 2.0 milliamps (mA) direct current through two bicarbon rubber electrodes encased in saline soaked 5 cm x 7 cm sponges (8 cc of 0.9% saline solution per sponge) placed over the frontal cortices at F3 and F4 (via 10-20 system).
Experimental: Cognitive Training + Sham Stimulation; This arm receives cognitive training combined with sham tDCS.	Behavioral: Cognitive Training; Computerized cognitive training targeting the underlying cerebral networks associated with depression.; Device: tDCS (sham stimulation); Sham stimulation will be performed with the same device and all procedures will be identical except for the duration of stimulation. Participants will receive 30 seconds of 2 mA of direct current stimulation at the beginning of the session. Participants habituate to the sensation of tDCS within 30-60 seconds of stimulation. This procedure provides the same sensation of tDCS without the full duration of stimulation, making it a highly effective sham procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NIH Examiner scores	This cognitive test battery assesses a range of executive functions (working memory, inhibition, set shifting, fluency, insight, and planning). The investigators will examine its Executive Composite Score, with higher scores indicate better performance.	From baseline to post-intervention (4-6 weeks)
Change in task-based fMRI activation within the Cognitive Control Network during the n-back task	MRI scans will be performed at baseline and after completion of the intervention. MRI will measure Cognitive Control Network function, operationalized as change in n-back functional MRI response in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and the posterior parietal cortex (PPC) regions of interest. The n-back functional MRI response is calculated as the activation difference (beta values) between 2-back and 0-back conditions of the n-back over time (post treatment - baseline). Higher scores indicate more activation. We will then examine correlations between the fMRI activity and n-back behavioral performance measures (accuracy, response time).	From baseline to post-intervention (4-6 weeks)
Change in n-back behavioral performance (accuracy and response time)	Target accuracy and response time data on the n-back will be extracted for each n-back condition (2-back and 0-back) and over time (baseline, post-intervention). Higher scores for the metrics indicate better accuracy but slower response time.	From baseline to post-intervention (4-6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in California Verbal Learning Test, 2nd edition (CVLT-2) scores	The CVLT-2 is a standardized measure of verbal learning and memory, with higher scores indicative of better learning and memory performances.	From baseline to post-intervention (4-6 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery Asberg Depression Rating Scale (MADRS) scores)	Clinician-rated measure of depression severity, with higher scores indicative of greater depression severity.	Baseline and weekly thereafter until post-intervention (4-6 weeks)

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: American Academy of Neurology
• Investigators: Principal Investigator: Sarah M. Szymkowicz, PhD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Actual): August 18, 2025
• Study Completion (Actual): August 18, 2025

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: May 27, 2022
• First Posted (Actual): June 1, 2022

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: memory; tDCS; depression; cognition; elderly; aging; cognitive remediation; geriatrics; cognitive training
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Behavioral Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Depression; Neurobehavioral Manifestations; Therapeutics; Patient Care; Health Services; Health Care Facilities Workforce and Services; Behavioral Disciplines and Activities; Rehabilitation; Aftercare; Continuity of Patient Care; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Neurological Rehabilitation; Transcranial Direct Current Stimulation; Cognitive Training
• Other Study ID Numbers: 220283

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes