Accelerated Age-related Cognitive Decline: Impact of Exercise on Executive Function and Neuroplasticity

Study Overview
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Brief Summary
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The purpose of this study is to see if 6 months of home-based walking will improve memory, and brain structure and function, compared to health education in older adults that have chronic kidney disease and mild cognitive impairment.

Detailed Description
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Following informed consent, participants will undergo tests for heart health, physical function, memory testing, and brain structure and function using imaging (taking pictures of the brain with an MRI). Following these tests participants are randomized to a home-based walking program or health education for 6 months. Participants are given a fitness tracker and gets ongoing telephone coaching during the 6 months. After 6 months the tests are repeated.

Official Title
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Accelerated Age-related Cognitive Decline: Impact of Exercise on Executive Function and Neuroplasticity

Conditions
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Mild Cognitive Impairment, Chronic Kidney Diseases

Intervention / Treatment
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* Behavioral: Home-based walking exercise
* Other: Attention control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Diagnosed stage 3-4 chronic kidney disease (CKD, estimated glomerular filtration rate (eGFR) <60 to 20 ml/min); >55 yrs of age Mild cognitive impairment (18-26 on the MOCA) ability to undergo an MR no history of major head trauma (No head trauma/concussion with loss of consciousness) Speaks, reads, writes English Exclusion Criteria: • Diagnosed Dementia or a Clinical Dementia Rating Scale score of <2, or a MOCA of <18 Participating in a supervised exercise program with intent to increase fitness levels 3 days/week, Requires assistive ambulation Limited exercise capacity due to claudication; unstable angina, severe arthritis, extreme dyspnea on exertion, unstable coronary artery disease Class III-IV heart failure History of uncontrolled sustained arrhythmias, severe/symptomatic aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy, severe pulmonary hypertension, active myocarditis/pericarditis, thrombophlebitis, and recent systemic/pulmonary embolus Resting systolic BP >200 mmHg or resting diastolic BP >110 mmHg Any unforeseen illness or disability that would preclude cognitive testing or exercise training One or more contraindication for MRI; cardiac pacemaker, aneurysm clip, cochlear implants, shrapnel, history of metal fragments in eyes, neurostimulators, diagnosed claustrophobia (MRI only) Any self-reported major psychiatric disorders requiring medical therapy (e.g. schizophrenia, bipolar disorder). Self-reported new diagnosis of clinical depression within 3 months of enrollment or unstable clinical depression requiring medication adjustment within 3 months of enrollment

Ages Eligible for Study
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Minimum Age: 55 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: Randomized controlled trial. Participants are randomized following baseline testing using block randomization of 2 and 4 to either an exercise intervention group or a health education group
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Home-based walking exercise<br>A 6-month partially supervised walking exercise training using a tapered approach. Participants begin with exercising (walking) in person, on-site one time per week and 3 times per week at home for a minimum exercise dosage of 30 minutes of accumulated exercise per session during month 1. During month 2, participants will exercise on-site once every other week and 3-4 times per week at home a minimum exercise dosage of 30 minutes of accumulated exercise per session. During months 2-6, participants will exercise at home 4 times per week for a minimum exercise dosage of 30 minutes of accumulated exercise per session and they will receive a phone call every two weeks to help coach and address any problems. Participants will receive a Fitbit fitness tracker that will be used to deliver their personalized exercise program, exercise monitoring, feedback, and motivational messages. | Behavioral: Home-based walking exercise<br>* A 6-month partially supervised walking exercise program using a tapered approach.Participants will begin exercise (walking) at a relatively low intensity and progress to moderate intensity. Intensity will start at 40% and progress as tolerated up to 60-70%. Rating of perceived exertion of 12-14 (fairly light to moderate) will be used to aid intensity (Rating of perceived exertion 6-20 scale). This is an accepted method for achieving desired exercise intensity. Participants will progress over time to exercise 3-4/week for 30-45 minutes. The exercise program may need to be adjusted for (e.g. 10 minutes of exercise 3 times), to achieve the minimum exercise dose of 30 minutes. This will be determined for each individual participants as needed.<br>|
| Placebo Comparator: Health education<br>The health education group will receive the same amount of contact hours as the intervention group. The attention control group will receive health education and stretching exercises. Participants will be in person, on-site one time per week during month 1 for about 30 minutes. During month 2, participants will attend the health education on-site once every other week for about 30 minutes. During months 2-6 participants will receive a phone call every two weeks to help remind about the health education. Participants will receive a Fitbit fitness tracker that will be used for exercise monitoring. | Other: Attention control<br>* Health education and stretching<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Executive Function from baseline | Composite score from Phonemic and Semantic Fluency total correct words; Trail Making Test Part B (TMT-B) time to completion; Digit Span subtest backwards total score. The composite executive functioning score will be created by converting these four individual executive cognitive scores (phonemic and Semantic fluency score), digit span backward subtest, and trail making test part B (following directionality conversion)) to standardized z scores and then averaging the standardized z scores. Z-score range from -3 to +3. Higher score is better. | Change from baseline at 6 months | 
| Change in processing speed from baseline | Trail making test part A (TMT-A) time to completion in seconds. Faster completion is better. | Change from baseline at 6 months | 
| Change in attention/information processing from baseline | Digit symbol substitution test total number correct. Higher number is better. | Change from baseline at 6 months | 
| Change in Learning and Memory short recall | California verbal learning test-II, short recall total number of words correct. Higher number is better. | Change from baseline at 6 months | 
| Change in Learning and Memory long recall | California verbal learning test-II long recall total number of words correct. Higher number is better. | Change from baseline at 6 months | 
| Change in Learning and Memory learning slope | California verbal learning test-II leaning slope (average number of new words recalled during five consecutive learning trials). Higher number is better. | Change from baseline at 6 months | 
| Change in Learning and Memory recognition memory discrimination | California verbal learning test-II recognition memory discrimination total number of words correct. Higher number is better. | Change from baseline at 6 months | 
| Change in global cognitive function | Composite score from Phonemic and Semantic Fluency total correct words; Trail Making Test Part B time to completion; Digit Span subtest backwards total score; Digit symbol substitution test total correct and trail making test part A time to completion; California verbal learning test-II, short and long recall, leaning slope, recognition memory discrimination total correct. The composite global cognitive score will be created by converting these 10 individual cognitive scores (following directionality change of TMT-A and TMT-B) to standardized z scores and then averaging the standardized z scores. Z score range from -3 to +3. Higher score is better. | Change from Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to 6-months in white matter fractional anisotropy. | Quantify change from baseline to 6-months in white matter integrity fractional anisotropy using diffusion tensor MRI imaging. Range 0-1. Higher number is better. | Change from baseline to 6 months | 
| Change from baseline to 6-months in white matter mean diffusivity. | Quantify change from baseline to 6-months in white matter integrity mean diffusivity using diffusion tensor MRI imaging. Range 0-1. Lower number is better. | Change from baseline to 6 months | 
| Changes from baseline to 6-months in functional connectivity | Quantify change from baseline to 6-months in functional connectivity using functional MRI (fMRI). Range 0-1. Higher score is better. | Change from Baseline to 6 months | 
| Change from baseline to 6-months in cerebral blood flow. | Quantify changes from baseline to 6-months in cerebral blood flow using perfusion MRI arterial spin labeling in mL/100g/min. Higher is better. | Change from baseline to 6 months | 
| Change from baseline to 6-months in hippocampal volume | Quantify change from baseline to 6-months in hippocampal volume using morphometry using 3D T1-weighted MRI in milliliters cubed. Higher number is better. | Change from baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild cognitive impairment, chronic kidney disease, exercise, Lifestyle behavior, home-based exercise