Cognitive Enhancement in Recurrent Depression (The COG-D-R Study)

The purpose of this study is to determine whether stepwise engagement of the frontal lobe across randomized groups (active tDCS+depression cognitive training > sham tDCS+depression cognitive training > sham tDCS+non-specific cognitive training) will result in progressively greater improvements in executive functions and memory, as well as intrinsic functional connectivity of the Executive Control Network (ECN), in older adults with recurrent depression. The investigators will randomize 69 elderly depressed outpatients into one of three conditions daily over 4-weeks. Psychiatric and neuropsychological evaluations, as well as multimodal neuroimaging (focused on the ECN) will be obtained at baseline and following intervention completion to look at acute and long-term effects.

• Depression Cognitive Training (Behavioral): Computerized cognitive training targeting the underlying cerebral networks associated with depression.
• Non-Specific Cognitive Training (Behavioral): Computerized cognitive training that provides extra stimulation for the brain that is non-specific.
• tDCS (active stimulation) (Device): 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).
• tDCS (sham stimulation) (Device): 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.

Primary outcomes

• NIH Examiner [Baseline, Following completion of the 4-week intervention, 3-month Post-Intervention]: This objective cognitive test battery assesses a range of executive functions (working memory, inhibition, set shifting, fluency, and planning). The investigators will examine intervention-related change its Executive Composite Score (primary outcome), and subcomposite (Cognitive Control, Working Memory, and Fluency; secondary outcomes) scores, where higher scores indicate better performance.
• Resting state fMRI functional connectivity [Baseline, Following completion of the 4-week intervention]: Functional connectivity from resting state fMRI will be processed using the CONN toolbox for connectivity, incorporating the Shaeffer network atlases to improve peer-research supported network usage in addition to the standard CONN atlases. A priori ROI-to-ROI analyses will be used to determine whether average connectivity changes in the Executive Control Network differs by treatment group. Analyses will control for multiple comparisons at false discovery rate (FDR) < 0.05.

Secondary outcomes

• Montgomery Asberg Depression Rating Scale [Baseline and weekly thereafter, Following completion of the 4-week intervention, 3-Month Post-Intervention]: The MADRS is a 10-item clinician-rated measure of depression severity, with higher scores indicating greater symptom severity. We will look at change in depression severity over the course of the intervention by treatment arm in Exploratory Analyses.

Sex: All, ages: 60 Years to any

Inclusion Criteria:

* Age > 60 years
* Evidence of executive dysfunction via SUBJECTIVE COMPLAINTS (At least one subdomain of the Behavior Rating Inventory of Executive Function in Adults (BRIEF-A) at T > 65, or At least one average score of > 1.5 on Planning, Organization, or Attention subdomains of the Everyday Cognition Scale (ECog)) or OBJECTIVE PERFORMANCE (At least one demographically adjusted z-score > -1.0 SD below the mean on a measure of executive functioning (Digits backward, Trails B, or total Verbal Fluency) on the National Alzheimer's Coordinating Center (NACC) Uniform Data Set 3.0).
* DSM-5 diagnosis of a current or past (within last 3 years) depressive episode (e.g., Major Depressive Disorder (MDD), Persistent Depressive Disorder (PDD)) via the using the Structured Clinical Interview for DSM-5 Disorders (SCID-5).
* Presence of 2 or more lifetime depressive episodes to be considered "recurrent."
* Either stable antidepressant regimen for at least 6 weeks or no current antidepressant treatment (no plans to change treatment over course of study).
* Fluent in English

Exclusion Criteria:

* Other psychiatric conditions via the SCID-5 (including history of bipolar disorder and psychosis, excluding comorbid anxiety disorders)
* Severe depression (MADRS score > 29)
* Acute suicidality on clinical evaluation by study clinician and via response on MADRS item 10 (score of 4 or more would require further assessment)
* Acute grief (occurring within past month)
* History of alcohol use disorder or substance use disorder of moderate or greater severity in the last 12 months
* Medications that would significantly interfere with tDCS effects (i.e., sodium channel blockers, GABA-ergic or glutamatergic drugs; see Appendix B for exclusionary list)40
* Primary neurological disorder (e.g., epilepsy, brain tumor, Parkinson's disease, Alzheimer's disease, dementia diagnosis)
* Montreal Cognitive Assessment (MoCA) < 23
* Primary amnestic cognitive profile (>1.5 SD below demographically-adjusted mean on NACC memory measures in context otherwise normal cognitive profile, or per clinician judgement)
* 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). Observational studies \[without intervention\] are acceptable.

• Informed Consent Form (PDF, 2026-03-11)