SMART Stimulation: Precision Neuromodulation of Cognition in Older Adults

• tDCS (Device): During tDCS, a weak electrical current is applied to the scalp that penetrates skin, bone, CSF and the meninges to stimulate underlying cortical and subcortical tissue
• cognitive training (Behavioral): Cognitive Training (CT) will involve up to 10 hours of training over 2-weeks (10 days). CT employs a PositScience BrainHQ suite via its researcher portal. These tasks are web-based and multi-platform (i.e., Windows, Mac). Participants will be randomly assigned to training on 4 tasks focusing on working memory or 4 tasks focusing on attention/speed of processing.

Primary outcomes

• N-Back Working Memory [Baseline to post test. Post test will occur approximately two weeks following baseline.]: Change in working memory performance on the N back working memory MRI task from baseline to post test will be assessed. Post test will occur approximately two weeks following baseline. The N-back working memory task will be completed during the MRI scan at both baseline and post test assessments. Working memory performance will be defined as a composite of reaction time and accuracy for two back trials. Specifically Target Accuracy percent correct and average correct target reaction time in milliseconds. Percent changes were calculated for Target Accuracy and Reaction Time in the form of (post test-pre test)/pre test. Since the direction of improvement is opposite for the two variables (i.e. higher Accuracy is better and lower Reaction Time is better), the reaction time percent change was multiplied by -1 to ensure a larger number indicated improved performance. To create a composite these two percent changes (Target Accuracy and Reaction Time) were averaged into a single value.

Sex: All, ages: 65 Years to 89 Years, accepts healthy volunteers

Inclusion Criteria:

* Men and women
* Age: 65 to 89 years
* English speaking
* Physically mobile
* Working memory function between 0-75th percentile determined by screening results on the POSIT Baseline Cognitive Training computerized tasks.

Exclusion Criteria:

* Neurological disorders (e.g., dementia, stroke, seizures, traumatic brain injury).
* Evidence of dementia (NACC UDS scores of 1.5 standard deviations below the mean for age, sex and education adjusted norms in a single cognitive domain on the task).
* Past opportunistic brain infection
* Major psychiatric illness (schizophrenia, intractable affective disorder, current substance dependence diagnosis or severe major depression and/or suicidality.
* Unstable (e.g., cancer other than basal cell skin) and chronic (e.g, severe diabetes) medical conditions.
* MRI contraindications (e.g., pregnancy, claustrophobia, metal implants that are contraindicated for MRI).
* Physical impairment precluding motor response or lying still for 1 hr and inability to walk two blocks without stopping.
* Certain prescription medications may possibly reduce effects otherwise induced by the tDCS stimulation protocol.
* Hearing or vision deficits that will not allow for standardized cognitive training stimulation; ie colorblindness, inability to hear through headphones (with or without hearing aids), macular degeneration or other significant diseases that cause severe loss of vision. If vision is corrected with lenses to appropriate levels, then participant will be eligible.
* Left handedness, as those with left-handedness have a higher percentage rate of atypical functional lateralization for brain functions, which would significantly interfere with interpretability of brain data.
* Participants with precision tDCS dosage of >4.0mA required will be excluded due to limitations of tDCS device (maximum output of 4.0 mA). The maximum output of 4.0 mA reflects a technical limitation of the device design rather than a safety threshold.

Participant flow

Outcome results

• N-Back Working Memory (Primary), Mean, percent change: Optimized tDCS + Cognitive Training .2030 +/- .3164; Sham tDCS + Cognitive Training .0731 +/- .1404

Adverse events

Time frame: 2 weeks. Adverse events were collected from study enrollment (week 0) until post-test (week 2).

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2023-09-19)