Aging, Depression, Cognitive Symptom
Conditions
Keywords
geriatrics, aging, elderly, cognition, memory, depression, tDCS, cognitive training, cognitive remediation
Brief summary
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).
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.
Interventions
BEHAVIORALCognitive Training
Computerized cognitive training targeting the underlying cerebral networks associated with depression.
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).
DEVICEtDCS (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.
Sponsors
Vanderbilt University Medical Center
American Academy of Neurology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Task-based fMRI Activation Within the Cognitive Control Network During the N-back Task | From baseline (T1) to post-intervention (4-6 weeks; T2) | MRI scans were performed at baseline (T1) and after completion of the intervention (4 to 6 weeks later; T2). MRI measured 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 was calculated as the activation difference (beta values) between 2-back and 0-back conditions of the n-back. Higher scores indicate more activation during the 2-back condition compared to the 0-back condition. |
| N-back Behavioral Performance (Accuracy) | From baseline (T1) to post-intervention (4-6 weeks; T2) | Target accuracy data on the n-back were extracted for each n-back condition (2-back and 0-back). Higher scores for the metrics indicated better accuracy. |
| N-back Behavioral Performance (Response Time) | From baseline (T1) to post-intervention (4-6 weeks; T2) | Target response time data on the n-back were extracted for each n-back condition (2-back and 0-back). Lower scores indicate faster response times. |
| NIH Examiner Scores | From baseline (T1) to post-intervention (4-6 weeks; T2) | Computerized neuropsychological battery to assess range of executive functions. The Executive Composite represents overall executive function performance across multiple neuropsychological measures. Item Response Theory (IRT) Empirical Bayes scoring based on the saved parameters from the 3 factors (Working Memory, Cognitive Control, Fluency) are used to generate scores, which are not a norm-referenced measure and are not adjusted for age. The composite is presented in the original metric used in the IRT algorithm. Scores range from -1.50 to 1.52. Higher scores mean better executive function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| California Verbal Learning Test, 2nd Edition (CVLT-2) Scores | From baseline (T1) to post-intervention (4-6 weeks; T2) | The California Verbal Learning Test, 2nd edition (CVLT-2) is a standardized measure of verbal learning and memory. Raw scores are obtained and converted to age and sex-adjusted z-scores, with 0 indicating population average. Positive values indicate of better than average learning and memory performances. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSarah M. Szymkowicz, PhD
Vanderbilt University Medical Center
Participant flow
Recruitment details
Participants were recruited from 2023-2025 via several mechanisms: clinical referrals at VUMC, advertisements (newspapers, internet, and flyers / brochures), and ResearchMatch.org.
Pre-assignment details
Participants underwent a comprehensive cognitive battery to ensure they did not have significant cognitive impairment that would affect their ability to participate (or would be meet exclusionary criteria). Medications were also reviewed, as certain medications would exclude them from the study. Medical conditions also had to be stable prior to assignment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 69.88 years STANDARD_DEVIATION 4.88 |
| Depression severity (via MADRS) at Baseline | 21.38 scores on a scale STANDARD_DEVIATION 7.67 |
| Depression severity (via MADRS) at Screening | 21.00 scores on a scale STANDARD_DEVIATION 8.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Executive functions (via NIH EXAMINER) at Baseline | 0.70 scores on a scale STANDARD_DEVIATION 0.41 |
| Montreal Cognitive Assessment (MoCA) | 26.75 scores on a scale STANDARD_DEVIATION 1.81 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 0 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
None listed