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

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

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

Loss of mobility and cognitive ability are serious conditions that threaten the independence of older adults. The objective of this study is to initiate a line of research to develop a novel therapeutic intervention to enhance both mobility and cognition via neuroplasticity of frontal/executive circuits.

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.

Participants will take part in a 6-week, 18-session neurorehabilitation led by qualified and trained study personnel. 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). Training logs will be maintained to gauge the content and intensity of training.

To control for intensity, participants will maintain a rating of perceived exertion of 4 (moderate to strong) on the Borg Category/Ratio Scale during walking. Exertion will be adjusted by modifying walking speed and/or by modifying the rest time between walking bouts.

Neurorehabilitation is a behavioral therapeutic approach for enhancing the neural control of task performance by: Restoration of function, specificity of training, Sensory input to the nervous system, Intensity, Repetition and Progression of training. Neurorehabilitation of standard walking will focus on the use of typical steady state walking.

Neurorehabilitation is a behavioral therapeutic approach for enhancing the neural control of task performance by: Restoration of function, specificity of training, Sensory input to the nervous system, Intensity, Repetition and Progression of training. Neurorehabilitation of complex walking will focus on the use of walking tasks that require increased attention and executive functions. The following walking tasks will be used: over obstacles, navigating around obstacles, changing speeds, on soft surfaces (exercise mat), in dim lighting, while conversing with the therapist, up/down ramps and climbing/descending stairs.

tDCS will be used to induce positive neuromodulation of frontal/executive circuits to make them more amenable to the "activity-dependent neuroplasticity" that is known to occur with behavioral neurorehabilitation. Specifically, tDCS may facilitate the efficacy of our walking neurorehabilitation intervention by strengthening the synaptic connections within the recruited circuits.

tDCS will be used to induce positive neuromodulation of frontal/executive circuits to make them more amenable to the "activity-dependent neuroplasticity" that is known to occur with behavioral neurorehabilitation. Specifically, tDCS may facilitate the efficacy of our walking neurorehabilitation intervention by strengthening the synaptic connections within the recruited circuits.

Time to complete a walking course at usual pace. The course is 15 feet in length and arranged as a Figure-8 pattern.

A battery of assessments that tests 7 domains of executive function separately and as a composite score.

Changes in prefrontal/executive activity during performance EXAMINER test to probe mechanisms of response

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

Chatterjee SA, Seidler RD, Skinner JW, Lysne PE, Sumonthee C, Wu SS, Cohen RA, Rose DK, Woods AJ, Clark DJ. Effects of Prefrontal Transcranial Direct Current Stimulation on Retention of Performance Gains on an Obstacle Negotiation Task in Older Adults. Neuromodulation. 2023 Jun;26(4):829-839. doi: 10.1016/j.neurom.2022.02.231. Epub 2022 Apr 8.