Cognitively engaging walking exercise and neuromodulation to enhance brain function in older adults - declines in cognitive function and walking function are highly intertwined in older adults

For instance, lower executive function exacerbates conversion to alzheimer's disease and is also associated with slow walking speed, instability, and falling. In turn, low levels of walking activity are a risk factor for age-related cognitive decline including alzheimer's disease. Combinatorial interventions that target both cognition and walking function may break this vicious cycle. Prefrontal networks are a crucial intervention target due to their role in executive function, which underlies performance of both complex cognitive tasks and complex walking tasks. Our research targets prefrontal neuroplasticity using a potent behavioral intervention of complex (cognitively engaging) aerobic walking exercise combined with frontal lobe transcranial direct current stimulation (tdcs). Tdcs is a mild form of electrical brain stimulation which may be an effective adjuvant for enhancing the effects of behavioral interventions on cognitive and motor function. The overarching hypothesis of our research is that tdcs delivered over prefrontal regions during complex walking exercise can improve both executive function and walking function. We have previously conducted a successful phase 1 study that demonstrated feasibility, safety, and positive behavioral outcomes from this intervention in older adults. Now we are proposing a phase 2 study that is designed to establish initial efficacy, investigate mechanisms of intervention response, and to develop a multi-site research infrastructure. We will enroll 104 older adult participants who have age-related cognitive decline. All participants will undergo the same 18-session high intensity aerobic walking program, which will emphasize the use of complex walking tasks that engage prefrontal cortex, such as obstacle negotiation and walking on compliant surfaces. Participants will be randomly assigned to a tdcs treatment group or sham control group. The treatment group will receive 20 minutes of 2MA tdcs over prefrontal regions F3/F4. The sham control group will receive just 30 seconds of 2MA tdcs at F3/F4 at the beginning of the session, which is known to be an effective sham procedure. A wearable stimulator will be used, so participants can receive stimulation while simultaneously performing the complex walking exercise. Specific aim 1 will establish efficacy of prefrontal tdcs as an adjuvant to complex walking exercise for enhancing executive function and walking function. Specific aim 2 will investigate mechanisms of response, including task-based prefrontal activity (with functional near infrared spectroscopy), MRI modeling of person-specific tdcs dosage, and their association with behavioral outcomes. The deliverable for this line of research will be a clinically- feasible multi-modal intervention for preserving function and independence in older adults.