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

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.

Inclusion Criteria:

- Slow gait, defined by an over-ground preferred walking speed of less than or equal to
0.90 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.

- Mild-to-moderate depressive affect, defined by a score of 5-11 on the Geriatric
Depression Scale.

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.