Exercise in Adults With Mild Memory Problems

Not Applicable

Completed

Conditions: Memory Impairment
Mild Cognitive Impairment
Cognitive Decline

Interventions: Behavioral: Aerobic exercise
Behavioral: Stretching/balance/range of motion exercise

Registration Number: NCT02814526

Lead Sponsor: Alzheimer's Disease Cooperative Study (ADCS)

Brief Summary: This study evaluates the effects of physical exercise on cognition, functional status, brain atrophy and blood flow, and cerebrospinal fluid biomarkers of Alzheimer's disease in adults with a mild memory impairment.

Half of participants will participate in a stretching-balance-range of motion exercise program, while the other half will participate in a moderate/high aerobic training program.

Detailed Description: Overall Study Design:

The EXERT trial was a multicenter phase 3 randomized, single-blind study that examined the effects of aerobic exercise on cognition, functional status, whole and regional cerebral blood flow, and cerebrospinal fluid biomarkers of Alzheimer's disease in approximately 300 adults with amnestic MCI. EXERT included an 18-month behavioral intervention trial, with a 12-month supervised exercise intervention phase with its primary endpoints, followed by a 6-month unsupervised exercised phase.

Subject Populations and Group Assignments:

The study population included male and female subjects aged 65 to 89 diagnosed with test scores and clinical ratings consistent with amnestic Mild Cognitive Impairment (MCI).

Assignment to study groups:

involved randomization to either treatment or active control, and study staff performing assessments were blinded to intervention assignment to maintain the single-blind structure of the trial.

Participants were to complete EXERT interventions at participating YMCAs located near the selected clinic sites across the U.S. The YMCA provided 18-month memberships at no cost to participants. In the first 12 months, a study-certified YMCA Trainer supervised all participants for the first 8 exercise sessions completed (weeks 1 and 2), and for 2 of 4 weekly sessions thereafter through Month 12. At Month 12, participants transitioned to independent exercise and were instructed to continue their assigned exercise programs for the final 6 months of the study without supervision. To encourage adherence and optimize cost efficiency, Trainers provided supervision to small groups of participants (2-4 individuals) randomized to the same intervention whenever possible. Compliance was evaluated using multiple mechanisms including heart rate monitoring, participant ratings of perceived exertion, entries in participants' Physical Activity Logs, Trainer assessment of effort, and weekly data review by the YMCA-Project Manager (Y-PM) and the Intervention Oversight Team (includes the Project Directors, Wake Forest team of exercise trial specialists, and Y-USA). These mechanisms provided multiple and regular opportunities to discuss participant progress, identify and resolve barriers, and encourage high levels of adherence to study protocols. The Intervention Oversight Team had the necessary expertise to successfully accomplish this objective in EXERT.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 296

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aerobic	Aerobic exercise	Moderate/high intensity aerobic exercise will involve training at 70-80% heart rate reserve for 30 min, with an additional 10 minutes for warm-up and 5 minutes for cool-down, 4 times per week, for 12 months while supervised twice per week by a study-certified trainer at a participating YMCA .
Stretching/balance/range of motion	Stretching/balance/range of motion exercise	The stretching/balance/range of motion program will involve exercise at or below 35% heart rate reserve for 30 min, with an additional 10 minutes for warm up and 5 minutes for cool-down, 4 times per week, for 12 months while supervised twice per week by a study-certified trainer at a participating YMCA.

Primary Outcome Measures

Name	Time	Method
ADAS-Cog-Exec Global Composite	Baseline to mean (Mo 6, Mo 12)	The ADAS-Cog-Exec Composite is a weighted sum of standardized (Z-score) change on subtests from the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog13; Immediate and Delayed Word Recall, Orientation, and Number Cancellation); box scores for the cognitive components of the Clinical Dementia Rating Scale (Memory, Orientation, Judgement \& Problem Solving); and additional tests requiring executive function (Trail Making Test A \& B, Digit Symbol Substitution, Category Fluency). See https://doi.org/10.1002/trc2.12059 for a detailed description regarding the development and validation of the ADAS-Cog-Exec. Change for the analysis of this primary outcome was calculated comparing the average of scores from month 6 and month 12 to baseline. The theoretical range for the ADAS-Cog-Exec is -3.00 to +3.00 in EXERT, with higher scores indicating improvement in cognitive function from baseline.

Secondary Outcome Measures

Name	Time	Method
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of Prefrontal Composite Region	Baseline to 12 Months	Assessment of change in blood flow activity in the prefrontal composite regions of the brain, measured using Arterial Spin Labeling (ASL) magnetic resonance imaging (MRI) scans. The prefrontal composite includes: superior frontal, caudal-middle frontal, rostral-middle frontal, pars opercularis, and pars triangularis regions. Scans taken at baseline and month 12 are compared and analyzed to assess change in blood flow. The unit of cerebral blood flow from ASL is ml/100g/min, which means the amount of blood flow into 100g of tissue during one minute.
AD Biomarkers in CSF (ab42/Tau)	12 Months	Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 12 months. A lower ab42/tau ratio is associated with a higher risk of dementia.
ADAS-Cog-Exec Global Composite in Subset Population	Baseline to mean (Mo 6, Mo 12)	The ADAS-Cog-Exec Composite is a weighted sum of standardized (Z-score) change on subtests from the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog13; Immediate and Delayed Word Recall, Orientation, and Number Cancellation); box scores for the cognitive components of the Clinical Dementia Rating Scale (Memory, Orientation, Judgement \& Problem Solving); and additional tests requiring executive function (Trail Making Test A \& B, Digit Symbol Substitution, Category Fluency). See https://doi.org/10.1002/trc2.12059 for a detailed description regarding the development and validation of the ADAS-Cog-Exec. Change for the analysis of this primary outcome was calculated comparing the average of scores from month 6 and month 12 to baseline. The theoretical range for the ADAS-Cog-Exec is -3.00 to +3.00 in EXERT, with higher scores indicating improvement in cognitive function from baseline.
Episodic Memory Composite Score	Baseline to mean (Mo 6, Mo 12)	The Episodic Memory Composite is the average standardized (Z-score) change on five measures of memory: Immediate and Delayed Word Recall from the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog13); Cogstate Face-Name Associative Memory; Cogstate Behavioral Pattern Separation of Objects; and Cogstate One Card Learning. Change for analysis of this secondary outcome was calculated comparing the average of scores from month 6 and month 12 to baseline. The theoretical range for the Episodic Memory Composite is -3.00 to +3.00, with higher scores indicating improvement in episodic memory from baseline.
Volumetric Magnetic Resonance Imaging (MRI) of Hippocampus	12 Months	Assessment of volumetric change in the hippocampus region of the brain, measured by structural Magnetic Resonance Imaging (MRI), comparing MRI scans taken at baseline and month 12. Scans are compared and analyzed to give a percent deformation between timepoints.
Volumetric Magnetic Resonance Imaging (MRI) of Prefrontal Composite Region	12 Months	Assessment of volumetric change in prefrontal composite regions of the brain, measured by structural Magnetic Resonance Imaging (MRI), comparing MRI scans taken at baseline and month 12. The prefrontal composite includes: superior frontal, caudal-middle frontal, rostral-middle frontal, pars opercularis, and pars triangularis regions. Scans are compared and analyzed to give a percent deformation between timepoints.
Executive Function Composite Score	Baseline to mean (Mo 6, Mo 12)	The Executive Function Composite is the average standardized (Z-score) change on eight measures requiring attention and executive control: Trail Making, Part B; Digit Symbol Substitution; Category Fluency; Letter Fluency; Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog13) Number Cancellation; NIH Toolbox Flanker; NIH Toolbox Dimension Change Card Sort, and Cogstate One Back. Change for analysis of this secondary outcome was calculated comparing the average of scores from month 6 and month 12 to baseline. The theoretical range for the Executive Function Composite is -3.00 to +3.00, with higher scores indicating improvement in executive function from baseline.
Ratio of AD Biomarkers in Blood	12 Months	Change in ratio of plasma amyloid beta peptides in blood plasma from baseline to12 months. A lower ab42/ab40 ratio in plasma is associated with a higher risk of dementia.
AD Biomarkers in CSF (ab42/ab40)	12 Months	Change in ratio of amyloid beta peptides in cerebrospinal fluid (CSF) from baseline to 12 months. A lower ab42/ab40 ratio is associated with a higher risk of dementia.
Volumetric Magnetic Resonance Imaging (MRI) of AD Signature Composite Region	12 Months	Assessment of volumetric change in Alzheimer's Disease (AD) signature regions of the brain, measured by structural Magnetic Resonance Imaging (MRI), comparing MRI scans taken at baseline and month 12. The AD signature composite includes: parahippocampus, fusiform, inferior temporal, middle temporal, and inferior-parietal regions. Scans are compared and analyzed to give a percent deformation between timepoints.
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of Hippocampus	Baseline to 12 Months	Assessment of change in blood flow activity in the hippocampus region of the brain, measured using Arterial Spin Labeling (ASL) magnetic resonance imaging (MRI) scans. Scans taken at baseline and month 12 are compared and analyzed to assess change in blood flow between the timepoints. The unit of cerebral blood flow from ASL is ml/100g/min, which means the amount of blood flow into 100g of tissue during one minute.
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of AD Signature Composite Region	Baseline to 12 Months	Assessment of change in blood flow activity in the Alzheimer's Disease (AD) signature regions of the brain, measured using Arterial Spin Labeling (ASL) magnetic resonance imaging (MRI) scans. The AD signature composite includes: parahippocampus, fusiform, inferior temporal, middle temporal, and inferior-parietal regions. Scans taken at baseline and month 12 are compared and analyzed to assess change in blood flow. The unit of cerebral blood flow from ASL is ml/100g/min, which means the amount of blood flow into 100g of tissue during one minute.
AD Biomarkers in CSF (ab42/P-tau)	12 Months	Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 12 months. A lower ab42/p-tau ratio is associated with a higher risk of dementia.

Trial Locations

Locations (14): Emory University
🇺🇸
Atlanta, Georgia, United States
University of California, Irvine
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Irvine, California, United States
Great Lakes Clinical Trials (Andersonville)
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Chicago, Illinois, United States
VAPAHCS / Stanford University School of Medicine
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Palo Alto, California, United States
New York University Medical Center
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New York, New York, United States
Mount Sinai School of Medicine
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New York, New York, United States
University of Kentucky
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Lexington, Kentucky, United States
University of Wisconsin
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Madison, Wisconsin, United States
University of North Texas Health Science Center
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Fort Worth, Texas, United States
Yale University School of Medicine
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New Haven, Connecticut, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
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Las Vegas, Nevada, United States
Duke University
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Durham, North Carolina, United States
Wake Forest University Health Sciences
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Winston-Salem, North Carolina, United States
University of Kansas Medical Center
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Kansas City, Kansas, United States