EXPRESS: Using Exercise and Electrical Brain Stimulation to Improve Memory in Dementia

Sponsor

Sunnybrook Health Sciences Centre (Other)

Overall Status

Recruiting

CT.gov ID

NCT03670615

Collaborator

(none)

Enrollment

Location

Arms

50.1

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment Alzheimer Disease	Other: tDCS Other: Exercise Other: Exercise Education Other: Sham tDCS	N/A

Detailed Description

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 primer with tDCS, Treatment as usual (TAU/exercise education) with tDCS, or Exercise primer with 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 fasting blood samples for biomarker analysis will be collected.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomized, blinded, repeated-session, parallel-design study.This is a randomized, blinded, repeated-session, parallel-design study.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

The research personnel that will be administering the cognitive assessments will be blinded to treatment allocation. The patients will be blinded to stimulation type.

Primary Purpose:

Treatment

Official Title:

Exercise as a Primer for Excitatory Stimulation Study (EXPRESS): A Combined Exercise and Transcranial Direct Current Stimulation Intervention for Cognition

Actual Study Start Date :

Nov 28, 2018

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exercise and tDCS 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 All study participants randomized to tDCS will receive active tDCS. Other: Exercise Participants will exercise at TRI according to an individualized exercise prescription.
Other: Exercise Education and tDCS Patients randomized to this group will undergo treatment as usual, receiving routine advice about physical activity and active tDCS intervention.	Other: tDCS All study participants randomized to tDCS will receive active tDCS. Other: Exercise Education Exercise education/ treatment as usual will include routine advice about physical activity for older adults. Other Names: Treatment as usual
Other: Exercise and Sham tDCS Patients randomized to this group will attend TRI-UHN for an individualized exercise program and sham tDCS intervention.	Other: Exercise Participants will exercise at TRI according to an individualized exercise prescription. Other: Sham tDCS The same procedure for tDCS will be used for the sham condition, except without active current.

Arm

Intervention/Treatment

Experimental: Exercise and tDCS

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

All study participants randomized to tDCS will receive active tDCS.

Other: Exercise

Participants will exercise at TRI according to an individualized exercise prescription.

Other: Exercise Education and tDCS

Patients randomized to this group will undergo treatment as usual, receiving routine advice about physical activity and active tDCS intervention.

Other: tDCS

All study participants randomized to tDCS will receive active tDCS.

Other: Exercise Education

Exercise education/ treatment as usual will include routine advice about physical activity for older adults.

Other Names:

Treatment as usual

Other: Exercise and Sham tDCS

Patients randomized to this group will attend TRI-UHN for an individualized exercise program and sham tDCS intervention.

Other: Exercise

Participants will exercise at TRI according to an individualized exercise prescription.

Other: Sham tDCS

The same procedure for tDCS will be used for the sham condition, except without active current.

Outcome Measures

Primary Outcome Measures

Change in global cognitive function: The Montreal Cognitive Assessment (MoCA) Total Scores [Change over 2 weeks (Midpoint to Endpoint)]
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.

Secondary Outcome Measures

Changes in concentration of blood biomarkers of brain plasticity [Change over 2 weeks (Midpoint to Endpoint)]
Biomarkers associated with exercise, tDCS outcomes, angiogenesis and neurogenesis will be obtained from blood work and analyzed using enzyme linked immunosorbent assays.

Other Outcome Measures

Change in neuropsychiatric symptoms: The Neuropsychiatric Inventory (NPI) [Change over 2 weeks (Midpoint to Endpoint)]
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 in cognition: n-back reaction time [Change over 2 weeks (Midpoint to Endpoint)]
A measure of working memory. Reaction times in milliseconds will be recorded. Higher values represent a worse outcome.
Change in cognition: n-back accuracy [Change over 2 weeks (Midpoint to Endpoint)]
A measure of working memory. Number of errors will be recorded. Higher values represent a worse outcome.
Change in cognition: The Word Recall Task from the Alzheimer's Disease Assessment Scale-Cog (ADAS-Cog) [Change over 2 weeks (Midpoint to Endpoint)]
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 in cognition: The Word Recognition Task from the Alzheimer's Disease Assessment Scale Cog (ADAS-Cog) [Change over 2 weeks (Midpoint to Endpoint)]
Assess recognition memory. Words incorrectly recognized will be tallied. Word Recognition scores range from 0 to 12. Higher scores represent a worse outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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