Exercise in Adults With Mild Memory Problems

NCT02814526 | Completed Results DMC

• 2 other identifiers: ADC-041-EXU19AG010483-22
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 14

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.

Conditions

Mild Cognitive Impairment; Cognitive Decline; Memory Impairment

Keywords

exercise

Outcome Measures

Primary Outcomes (1)

• ADAS-Cog-Exec Global Composite

  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.

  Baseline to mean (Mo 6, Mo 12)

Secondary Outcomes (13)

• ADAS-Cog-Exec Global Composite in Subset Population

  Baseline to mean (Mo 6, Mo 12)

• Executive Function Composite Score

  Baseline to mean (Mo 6, Mo 12)

• Episodic Memory Composite Score

  Baseline to mean (Mo 6, Mo 12)

• Volumetric Magnetic Resonance Imaging (MRI) of Hippocampus

  12 Months

• Volumetric Magnetic Resonance Imaging (MRI) of Prefrontal Composite Region

  12 Months

Other Outcomes (6)

• Intervention Effects on Secondary Outcomes in a Subset of Participants Who Completed 12 Months of the Study Prior to the COVID-19 Pandemic.

  12 months

• Exploratory Magnetic Resonance Imaging (MRI) Volumes and Perfusion and Individual AD Biomarkers in CSF and Blood Measures

  12 Months

• Clinical Dementia Rating Scale-Sum of Boxes (CDR) and Alzheimers Disease Assessment Scale-Cognitive 13-item (ADAS-Cog13)

  12 Months

Study Arms (2)

Aerobic

EXPERIMENTAL

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 .

Behavioral: Aerobic exercise

Stretching/balance/range of motion

ACTIVE COMPARATOR

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.

Behavioral: Stretching/balance/range of motion exercise

Interventions

Aerobic exercise BEHAVIORAL

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 .

Aerobic

Stretching/balance/range of motion exercise BEHAVIORAL

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.

Stretching/balance/range of motion

Eligibility Criteria

• Age: 65 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age between 65 and 89 years old, inclusive
• MMSE: ≥24 for participants with 13 or more years of education; ≥22 for participants with 12 or fewer years of education
• Global CDR score of 0.5 with a memory score of at least 0.5
• Profile of test scores and clinical ratings is consistent with amnestic mild cognitive impairment
• Speaks English fluently
• Visual and auditory acuity adequate for cognitive testing
• Completed at least 6 years of formal education or work history sufficient to exclude mental retardation
• Has an informant who knows the participant well, has regular contact, and is available to accompany the participant to clinic visits or complete study partner assessments remotely.
• Sedentary or underactive, determined by responses to the staff-administered EXERT Telephone Assessment of Physical Activity (TAPA) survey
• Willing to be randomized to either intervention group and to complete the assigned activities as specified for 18 months
• Willing and able to reliably travel to the identified YMCA, 4 times per week for 18 months
• Ability to safely participate in either intervention and complete the 400 m Walk Test within 15 min without sitting or use of any assistance
• Plans to reside in the area for at least 18 months
• For planned travel, total time away must be no more than 2 months over the course of the study, and no more than 1 month at any one time; participants must be willing to continue the assigned exercise program if travelling out of the area for more than 1 week
• In overall good general health with no disease or planned surgery that could interfere with study participation

You may not qualify if:

• Any significant neurologic disease, other than MCI, including any form of dementia, Parkinsons disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities
• Sensory or musculoskeletal impairment sufficient to preclude successful and safe completion of the intervention or assessment protocols; must be able to walk safely and unassisted on a treadmill
• Contraindications for MRI studies, including claustrophobia, metal (ferromagnetic) implants, or cardiac pacemaker
• Brain MRI at screening shows evidence of infection, infarction, or other clinically significant focal lesions, including multiple lacunes in prefrontal or critical memory regions; inconclusive findings may be subject to review by the ADCS Imaging Core
• History of major depression or bipolar disorder (DSM V criteria), psychotic features, agitation or behavioral problems within the last 12 months
• History of schizophrenia, as per DSM V criteria
• History of alcohol or substance abuse or dependence within the past 2 years, as per DSM V criteria
• Currently consumes more than 3 alcoholic drinks per day
• History in the last 6 months of myocardial infarction, coronary artery angioplasty, bypass grafting, or STENT placement
• History in the last 3 months of transient ischemic attack or small vessel stroke (if more than 3 months, small vessel stroke with no residual effects are permitted)
• Expected joint replacement surgery within the next 18 months
• History within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen posttreatment
• Hemoglobin A1c \>7.0
• Current or past use of insulin to treat type 2 diabetes (other diabetes medications are acceptable if hemoglobin A1c ≤7)
• Current use (within 60 days of screening) of psychoactive medications including tricyclic antidepressants, antipsychotics, mood-stabilizing psychotropic agents (e.g. lithium salts), psychostimulants, opiate analgesics, antiparkinsonian medications, anticonvulsant medications (except gabapentin and pregabalin for non-seizure indications), systemic corticosteroids, or medications with significant central anticholinergic activity. Limited use of antipsychotics (quetiapine ≤ 50mg/day or risperidone ≤ 0.5mg/day), and non-chronic use of opiate analgesics on an as needed basis is permitted; such medications must be avoided for 8 hours before clinic assessments

Sponsors & Collaborators

• Alzheimer's Disease Cooperative Study (ADCS): lead
• National Institute on Aging (NIA): collaborator
• Wake Forest University Health Sciences: collaborator

Study Sites (14)

University of California, Irvine

Irvine, California, 92697, United States

Location

VAPAHCS / Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Great Lakes Clinical Trials (Andersonville)

Chicago, Illinois, 60640, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66205, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of North Texas Health Science Center

Fort Worth, Texas, 76107, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (8)

• Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Plymate SR, Fishel MA, Watson GS, Cholerton BA, Duncan GE, Mehta PD, Craft S. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010 Jan;67(1):71-9. doi: 10.1001/archneurol.2009.307.

  PMID: 20065132 BACKGROUND

• Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, Greenop KR, Almeida OP. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA. 2008 Sep 3;300(9):1027-37. doi: 10.1001/jama.300.9.1027.

  PMID: 18768414 BACKGROUND

• Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, Elavsky S, Marquez DX, Hu L, Kramer AF. Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci. 2006 Nov;61(11):1166-70. doi: 10.1093/gerona/61.11.1166.

  PMID: 17167157 BACKGROUND

• Voss MW, Prakash RS, Erickson KI, Basak C, Chaddock L, Kim JS, Alves H, Heo S, Szabo AN, White SM, Wojcicki TR, Mailey EL, Gothe N, Olson EA, McAuley E, Kramer AF. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci. 2010 Aug 26;2:32. doi: 10.3389/fnagi.2010.00032. eCollection 2010.

  PMID: 20890449 BACKGROUND

• Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E, Kramer AF. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci. 2003 Feb;58(2):176-80. doi: 10.1093/gerona/58.2.m176.

  PMID: 12586857 BACKGROUND

• Burns JM, Cronk BB, Anderson HS, Donnelly JE, Thomas GP, Harsha A, Brooks WM, Swerdlow RH. Cardiorespiratory fitness and brain atrophy in early Alzheimer disease. Neurology. 2008 Jul 15;71(3):210-6. doi: 10.1212/01.wnl.0000317094.86209.cb.

  PMID: 18625967 BACKGROUND

• Nichol KE, Poon WW, Parachikova AI, Cribbs DH, Glabe CG, Cotman CW. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid. J Neuroinflammation. 2008 Apr 9;5:13. doi: 10.1186/1742-2094-5-13.

  PMID: 18400101 RESULT

• Shadyab AH, Aslanyan V, Jacobs DM, Salmon DP, Morrison R, Katula JA, Jin S, Thomas RG, LaCroix AZ, Pa J, Cotman CW, Feldman HH, Baker LD; ADCS EXERT Study Group. Effects of exercise versus usual care on older adults with amnestic mild cognitive impairment: EXERT versus ADNI. Alzheimers Dement. 2025 Apr;21(4):e70118. doi: 10.1002/alz.70118.

  PMID: 40271887 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Memory Disorders; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Results Point of Contact

• Title: Clinical Operations
• Organization: Alzheimer's Disease Cooperative Study (ADCS)

alzinfo@ucsd.edu

858-246-1333

Study Officials

• Howard Feldman, MDCM FRCP(C)

  Alzheimer's Disease Cooperative Study (ADCS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 27, 2016
• Study Start: September 13, 2016
• Primary Completion: November 17, 2021
• Study Completion: December 19, 2021
• Last Updated: February 15, 2023
• Results First Posted: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 01 March 2023
• Access Criteria: Data requestors must complete an ADCS data and sample sharing request form. Upon approval, requestors must complete a data use agreement prior to accessing the data.

Locations

US (14)