Combining tDCS and Neurorehabilitation to Treat Age-related Deficits of Mobility and Cognition: UPfront Walking Study

Frontal lobe dysfunction has been implicated as a factor contributing to gait deficits in
some individuals with Alzheimer's disease, frontotemporal dementia and vascular dementia.
There is a critical gap in knowledge about what therapeutic strategies are effective for
maintaining or reinstating function in this critical brain region in order to preserve
physical and cognitive health in older adults. The goal of our research is to develop a novel
therapeutic intervention to enhance both mobility and cognition via neuroplasticity of
frontal/executive control circuits. The Investigator will engage neuroplasticity of frontal
circuits in two ways. The first is through neurorehabilitation with "complex walking tasks"
(CWTs), such as obstacle crossing, obstacle avoidance and walking on non-uniform surfaces.
CWTs are a potent behavioral approach for engaging prefrontal circuits. Furthermore, CWTs are
crucial to successful ambulation in the home and community settings and therefore provide an
ecologically valid therapeutic approach. The second approach that the Investigator will use
to engage neuroplasticity of frontal circuits is anodal transcranial direct current
stimulation (tDCS). Anodal tDCS is a safe, non-invasive neuromodulation technique. It has
previously been shown to induce excitatory effects on brain tissue and, in single-session
assessments, to improve performance during complex walking tasks. tDCS has also been shown to
be an effective adjuvant for enhancing the effects of cognitive training. The objective of
this study is to calculate effect size, establish variance of response and demonstrate
feasibility of the experimental interventions in order to plan for a full scale clinical
trial. Participants will include thirty older adults who demonstrate evidence of
frontal/executive impairment. Participants will be randomized to one of three groups: 1)
standard walking neurorehabilitation with sham tDCS ('standard/sham' group), 2) complex
walking neurorehabilitation with sham tDCS ('complex/sham' group), or 3) complex walking
neurorehabilitation with active anodal tDCS ('complex/active' group). Functional near
infrared spectroscopy (fNIRS) will be used to explore intervention-induced changes in
prefrontal cortical activity. Assessments will be conducted at baseline, post-treatment and
3-month follow up. The Investigator propose the following specific aims:

Specific Aim 1: Determine preliminary efficacy for recovery of mobility and cognitive
function.

Specific Aim 2: Demonstrate feasibility/safety of tDCS as an adjuvant to rehabilitation.

Specific Aim 3: Explore the relationship between prefrontal activity and behavioral outcomes
The data collected here will provide the information needed to justify and plan a future full
scale clinical trial to assess the relative efficacy and underlying mechanisms of each
intervention approach.

Inclusion criteria

- preferred 10m walking speed < 1.0 m/s

- 40th-80th percentile rank (age and education corrected score) on NIH toolbox executive
assessments: Card Sort Test and Flanker test

- willingness to be randomized to either intervention and to participate in all aspects
of study assessment and intervention

Exclusion criteria

- contraindications to non-invasive brain stimulation and/or MRI including metal in the
head, pacemaker, known abnormal cranial fissures/holes.

- difficulty communicating with study personnel

- uncontrolled hypertension at rest (systolic > 180 mmHg and/or diastolic > 100 mmHg)

- low vision that cannot be corrected by wearing glasses. Low visual will be
operationally defined as visual acuity less than 20/70 on a standard eye chart, or
difficulty performing complex walking tasks due to visual conditions affecting
accurate navigation around and over obstacles (self-reported or observed by examiner).

- illiterate, due to the likelihood of difficulties performing some of the cognitive
tasks

- non-English speaking, due to the likelihood of difficulties following instructions
during therapy and during assessments

- use of medications that are know to modify tDCS effectiveness including those with
anticholinergic, GABAergic, or glutamatergic properties, or sodium channel blockers

- clinical judgment of investigative team