Using Exercise and Electrical Brain Stimulation to Improve Memory in Dementia

Study Overview
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Brief Summary
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Mild cognitive impairment and Alzheimer's disease are conditions that involve memory difficulties. Transcranial direct current stimulation is a type of brain stimulation. It may help improve these memory difficulties. However, it works better on active brain areas. This study looks at if combining exercise and applying current to important parts of the brain can help improve memory in people with Mild Cognitive Impairment or Alzheimer's disease.

Detailed Description
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Objectives: To assess the efficacy of a combined exercise and tDCS treatment for improving cognitive outcomes in mild cognitive impairment and mild Alzheimer's disease. Study Design: Eligible participants will be randomized to one of three interventions: Exercise and tDCS, Treatment as usual (TAU/exercise education) and tDCS, or Exercise and sham tDCS. Participants randomized to an exercise group will undergo exercise, followed by either sham or active tDCS. Participants randomized to TAU will receive written information in accordance with the Canadian Physical Activity Guidelines for older adults and tDCS for the same duration. Cognition, neuropsychiatric symptoms and blood samples for biomarker analysis will be collected.

Official Title
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Exercise Augmenting Cognition tDCS (EXACT): A Pilot Study of a Combined Exercise and Transcranial Direct Current Stimulation Intervention for Cognition

Conditions
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Mild Cognitive Impairment, Alzheimer Disease

Intervention / Treatment
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* Other: tDCS
* Other: Exercise
* Other: Exercise Education
* Other: Sham tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥50 years of age DSM-5 criteria for major or mild neurocognitive disorder due to AD or mixed AD/vascular disease Mild severity of impairment (standardized Mini-Mental State Examination (MMSE) score ≥19) Read and communicate in English Exclusion Criteria: Change in cognitive enhancing medications (ChEIs and/or memantine) less than 3 months prior to study screen Change in anticonvulsants or psychotropic medications less than 1 month prior to study screen Currently taking benzodiazepines Presence of metal implants that would preclude safe use of tDCS (e.g. pace-maker) Significant neurological condition (e.g. epilepsy, Parkinson's disease, multiple sclerosis) Current psychiatric disorders (e.g. schizophrenia, bipolar disorder, depression, psychosis) or current substance use disorder Medical contraindications to increasing activity level according to the Canadian Society of Exercise Physiology Questionnaire

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, blinded, repeated-session, parallel-design study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise and tDCS<br>Patients randomized to this group will attend Toronto Rehabilitation Institute - University Health Network (TRI-UHN) for an individualized exercise program and active tDCS intervention. | Other: tDCS<br>* All study participants randomized to tDCS will receive active tDCS.<br>Other: Exercise<br>* Participants will exercise at TRI according to an individualized exercise prescription.<br>|
| Other: Exercise Education and tDCS<br>Patients randomized to this group will undergo treatment as usual, receiving routine advice about physical activity and active tDCS intervention. | Other: tDCS<br>* All study participants randomized to tDCS will receive active tDCS.<br>Other: Exercise Education<br>* Exercise education/ treatment as usual will include routine advice about physical activity for older adults.<br>* Other names: Treatment as usual;|
| Other: Exercise and Sham tDCS<br>Patients randomized to this group will attend TRI-UHN for an individualized exercise program and sham tDCS intervention. | Other: Exercise<br>* Participants will exercise at TRI according to an individualized exercise prescription.<br>Other: Sham tDCS<br>* The same procedure for tDCS will be used for the sham condition, except without active current.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognition: The Word Recognition Task from the Alzheimer's Disease Assessment Scale Cog (ADAS-Cog) | Assess recognition memory. Words incorrectly recognized will be tallied. Word Recognition scores range from 0 to 12. Higher scores represent a worse outcome. | Change over 2 weeks (Baseline to Endpoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognition: n-back reaction time | A measure of working memory. Reaction times in milliseconds will be recorded. Higher values represent a worse outcome. | Change over 2 weeks (Baseline to Endpoint) | 
| Change in cognition: The Word Recall Task from the Alzheimer's Disease Assessment Scale-Cog (ADAS-Cog) | Assesses recall memory. Number of words not recalled will be tallied. Word recall scores range from 0 to 10. Higher scores represent a worse outcome. | Change over 2 weeks (Baseline to Endpoint) | 
| Change in global cognitive function: The Montreal Cognitive Assessment (MoCA) Total Scores | A brief measure of global cognition that includes assessments of orientation, short-term total memory, executive function, language abilities, attention and visuospatial ability. MoCA scores range from 0 to 30. Higher scores represent a better outcome. | Change over 2 weeks Baseline to Endpoint | 
| Change in neuropsychiatric symptoms: The Neuropsychiatric Inventory (NPI) | A widely used assessment of behavior disturbances in dementia including: apathy, agitation, delusions, hallucinations, depression, euphoria, aberrant motor behavior, irritability, disinhibition, anxiety, sleeping, and eating. Frequency and severity of each symptom is measured using subscales. Frequency and severity are judged using a 4-point scale (ranging from 1-4) and 3-point scale (ranging from 1-3) respectively. A 6-point scale for each symptom is used to evaluate caregiver distress (ranging from 0-5). Higher values represent a worse outcome. | Change over 2 weeks (Baseline to Endpoint) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer disease, cognition, transcranial direct current stimulation, exercise, mild cognitive impairment