The Effects of Noninvasive Brain Stimulation on Physical and Mental Functioning in Older Adults

The objective of this study is to determine whether augmentation of prefrontal brain excitability using noninvasive transcranial direct current stimulation (tDCS) lessens the severity of the symptom triad associated with cerebral microvascular disease (CMD); that is, slow gait, cognitive dysfunction and depressive symptoms. Investigators will complete this objective by conducting a pilot, double-blinded randomized controlled trial of a 10-day intervention of real versus sham tDCS in 40 subjects.

Biological aging, especially when coupled with cardiovascular risk factors, leads to chronic endothelial dysfunction within cerebral micro-vessels that impairs the brain's ability to meet the metabolic demands placed upon it by everyday life. This chronic mismatch between blood supply and metabolic demand often leads to cerebral microvascular disease (CMD), or the accumulation of ischemic damage within a network of frontal and subcortical regions. CMD is recognized as white matter hyperintensities on MRI scans and manifests clinically as mobility impairment, executive dysfunction and depressed affect. As 11-17% of elderly individuals present with this constellation of symptoms, and each of these symptoms is independently linked to increased morbidity and mortality, CMD is a critical yet understudied healthcare issue with rapidly-growing personal and economic costs.

There is currently no cure for CMD and trials aimed at pharmacological improvement of nonselective systemic vasodilation report no therapeutic value (Sorrond \& Lipsitz, 2011). Our team, however, has demonstrated that the severity of clinical symptoms suffered by those with CMD is critically dependent upon the brain's remaining capacity to activate the appropriate cortical networks when metabolic demand is increased by the performance of various cognitive-motor tasks (Purkayastha et al., 2014; Sorond et al., 2010; Sorond et al., 2011). Therefore, investigators predict that improvement in the capacity to activate the appropriate cortical networks in response to increased metabolic demand would ameliorate the symptoms and improve the quality of life of patients with CMD.

Transcranial direct current stimulation (tDCS) enables noninvasive, selective and sustained modulation of cortical activation. tDCS works by sending low-level currents between two or more scalp electrodes, which alters brain polarity and thus, perfusion and cortical excitability. One 20-minute session of tDCS targeting the left prefrontal cortex acutely increases cortical activation during both cognitive and motor task performance in healthy adults. Investigators have demonstrated that this same stimulation improves mobility and cognitive performance in community-dwelling older adults. Moreover, repeated tDCS sessions over a one month period reduce symptoms of depression and may improve executive function in healthy individuals. This preliminary evidence suggests that tDCS may be an effective intervention for CMD; however, the impact of tDCS on this disease has not been investigated.

The study investigators ultimately aim to investigate the therapeutic efficacy of tDCS in patients with CMD by conducting a double-blind, proof-of-principle, sham-controlled trail along with extensive functional and neurophysiological assessments. In order to finalize the design and plan the implementation of this definitive trial, investigators currently aim to:

1. Conduct a pilot study to establish the feasibility of deployment of tDCS in large populations of individuals with CMD, and to obtain preliminary evidence for a causal effect of the intervention on mobility, executive function and depressive symptoms in this population.
2. Within the pilot study, investigate the effects of the tDCS intervention on cortical activation in response to cognitive-motor tasks.

This study will provide first-of-its-kind, proof-of-principle evidence on whether tDCS provides meaningful symptomatic relief to patients with CMD. Moreover, it will inform a more definitive, larger-scale randomized controlled trial (RCT) by providing information on recruitment and retention, compliance, estimates of effect size, and the neurophysiological underpinnings of expected functional improvements. If successful, knowledge gained is also expected to spur the investigation of tDCS as treatment for many other diseases-from dementia to diabetes-that negatively impact the brain's capacity to activate appropriate cortical networks.

Eligibility Criteria:
Inclusion Criteria:

* Slow gait, defined by an over-ground preferred walking speed of less than or equal to 1.0 m/s.
* Executive dysfunction, defined by a Trail Making Test B z-score of greater than one standard deviation below age- and gender-based norms.

Exclusion Criteria:

* Non-ambulatory
* Clinical history or brain imaging evidence of a previous stroke
* Parkinson's Disease
* Normal pressure hydrocephalus
* Other neurodegenerative condition
* Severe depression
* Lower-extremity arthritis or pain causing slow gait
* Inability or unwillingness to understand or participate in the study protocol
* Contraindications to MRI or tDCS, including (but not limited to) personal or family history of epilepsy, use of neuro-active drugs, claustrophobia or risk of metal objects in the body.