Long-term home-based transcranial electrical stimulation for cognitive and motor function in older adults with an increased risk of dementia: a randomized controlled trial - motoric cognitive risk…

Long-term home-based transcranial electrical stimulation for cognitive and motor function in older adults with an increased risk of dementia: a randomized controlled trial - motoric cognitive risk (MCR) is a transition state between "normal" aging and alzheimer's disease and related dementias (ad/ADRD). Older adults with MCR have an increased risk of developing ad/ADRD. They suffer from brain atrophy in the dorsolateral prefrontal cortex (DLPFC)-a brain region subserving executive function-and have abnormal DLPFC activation when walking and performing a cognitive task (i.e., dual-tasking, DT), an executive function that predicts incident ad/ADRD. MCR thus identifies an opportunity to intervene (UPSTREAM) to alter the trajectory of cognitive decline and the risk of ad/ADRD in later life. In a series of pilot studies, we have shown that transcranial direct current stimulation (TDCS) improves dual-tasking gait, executive function, and related outcomes. These short-term studies are encouraging. Yet, the extent to which TDCS can induce longer-term benefits is unclear. We have also shown that TDCS can be administered safely in the home and that a smartphone APP can be used for home-based testing of DT gait. We will enroll 128 older adults into a sham-controlled, double-blinded, delayed-start, multi-site clinical trial of home-based TDCS, with stimulation parameters tailored to target the anatomically defined left DLPFC of each participant. After an initial open-label 2-week TDCS intervention, participants will be randomized into a TDCS arm (5 weekly TDCS sessions for 6 months), or a delayed-start sham arm (5 weekly sham sessions for 3 months before switching to 5 weekly sessions of TDCS for 3 months). In-lab assessments will be conducted at baseline, after the initial 2-week intervention, after 3 and 6 months of stimulation, and 3 months later. Structural and functional mris will be acquired at baseline and 3 months. The primary endpoint will be DT cost (DTC) to gait speed, a cognitive-motor marker of prefrontal function and predictor of future cognitive decline. Our primary hypothesis is that compared to sham, the TDCS arm will exhibit lower (BETTER) DTC to gait speed after 3 months of continued stimulation. We also expect that TDCS, compared to sham, will lead to BETTER performance on other tests of executive and cognitive function, reduced (more efficient) DLPFC activation when walking, and measurable changes in prefrontal structure and functional connectivity as measured by MRI. The delayed-start trial design will further enable US to test the hypotheses that the benefits of TDCS accumulate over time, and that the rate of decline of benefits is slower after six months, as compared to only three months of use. Finally, we will utilize weekly, home-based gait assessments using our APP throughout the RCT-and for 3 months after-to establish individual and group trajectories of change in the DTC to gait speed over time, allowing US to address many critical unknowns (e.g., if and when do the benefits of 2-weeks, 3-months, and 6-months of TDCS wear off, and if so, at what rate?). We anticipate showing that home-based TDCS is an effective, long-term therapeutic option capable of inducing sustained improvements in cognitive and motor function, as well as left DLPFC structure and function, in older adults at risk of developing ad/ADRD.