Mild Cognitive ImpairmentEXERTNCT02814526

Exercise in Adults With Mild Memory Problems

A study testing Aerobic exercise and Stretching/balance/range of motion exercise in people with Mild Cognitive Impairment and Cognitive Decline, run by Alzheimer's Disease Cooperative Study (ADCS) at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 65 to 89 years
Conditions the study is for: Mild Cognitive Impairment, Cognitive Decline, Memory Impairment
What is being tested?: Aerobic exercise and Stretching/balance/range of motion exercise
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 296 participants
Where: 14 sitesUnited States
Study dates: 13 Sep 2016to 19 Dec 2021
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 65 to 89 years
All sexes
No healthy volunteers
Older adult

Who may be able to join

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

Show all 20Show fewer

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
Modified Hachinski ≤4
Stable use of cholinesterase inhibitors, memantine, vitamin E, estrogens, aspirin (81 300 mg daily), beta-blockers, or cholesterol-lowering agents for 12 weeks prior to screening (important for biomarker analyses)
Stable use of antidepressants lacking significant anticholinergic side effects for 4 weeks prior to screening as long as the participant does not meet DSM V criteria for major depression currently or in the last 12 months; GDS scores are to be used to inform clinical decisions but there is no specified cut-off score for inclusion
When applicable, willing to complete 4-week washout of psychoactive medications, including disallowed antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, and willing to avoid these medications for the duration of the trial
Able to complete all baseline assessments

Who cannot join

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

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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
Clinically significant or unstable medical condition, including uncontrolled hypertension or significant cardiac, pulmonary, hematologic, renal, hepatic, gastrointestinal, endocrine, metabolic or other systemic disease in the opinion of clinic medical personnel that may put the participant at increased risk, influence the results or compromise the participants ability to participate in the study (treated atrial fibrillation for more than 1 year or occasional premature ventricular contractions on ECG are not exclusions)
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
Clinically significant abnormalities in screening laboratory blood tests: low B12 is exclusionary, unless follow-up labs (homocysteine [HCY] and methylmalonic acid [MMA]) indicate that it is not physiologically significant
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
Chronic use of anxiolytics or sedative hypnotics except as follows: use of benzodiazepines for treatment on an as-needed basis for insomnia or daily dosing of anxiolytics is permitted; medications must be avoided for 8 hours before clinic assessments
Previous or current treatment involving active immunization against amyloid
Previous treatment with approved or investigational agents with anti-amyloid properties or passive immunization against amyloid are prohibited 12 months prior to screening and for the duration of the trial; treatment with other investigational agents are prohibited 3 months prior to screening and for the duration of the trial
For LP, current use of anticoagulants such as Coumadin, Plavix, or high dose Vitamin E
For LP, current blood clotting or bleeding disorder, or significantly abnormal prothrombin time (PT) or partial thromboplastin time (PTT) at screening
For LP, presence of physical distortions due to spinal surgery, severe degenerative joint disease or deformity, or obesity that could interfere with CSF collection (as per investigator judgment)
Participants whom the PI deems otherwise ineligible

Trial locations and contacts

14 sites in 1 country.

City, postcode or hospital

14 sites in 1 country

United States14 sites

Emory University
Atlanta, Georgia, 30329
Great Lakes Clinical Trials (Andersonville)
Chicago, Illinois, 60640
Duke University
Durham, North Carolina, 27705
University of North Texas Health Science Center
Fort Worth, Texas, 76107
University of California, Irvine
Irvine, California, 92697
University of Kansas Medical Center
Kansas City, Kansas, 66205
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, 89106
University of Kentucky
Lexington, Kentucky, 40536
University of Wisconsin
Madison, Wisconsin, 53792
Yale University School of Medicine
New Haven, Connecticut, 06510
New York University Medical Center
New York, New York, 10016
Mount Sinai School of Medicine
New York, New York, 10029
VAPAHCS / Stanford University School of Medicine
Palo Alto, California, 94304
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Therapeutic Effects of Exercise in Adults With Amnestic Mild Cognitive Impairment (MCI)

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.

Read the 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.

Conditions: Mild Cognitive Impairment, Cognitive Decline, Memory Impairment
Being tested: Aerobic exercise, Stretching/balance/range of motion exercise
Keywords: exercise
Medical subject headings: Cognitive Dysfunction, Memory Disorders, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Aerobic exerciseBehavioural
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 exerciseBehavioural
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.

Study groups in NCT02814526
Study group	Role	What they receive
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 . Receives: 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. Receives: Behavioral: Stretching/balance/range of motion exercise

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to mean (Mo 6, Mo 12)

Secondary outcomes (13)

ADAS-Cog-Exec Global Composite in Subset Population
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.
Measured: Baseline to mean (Mo 6, Mo 12)
Executive Function Composite Score
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.
Measured: Baseline to mean (Mo 6, Mo 12)
Episodic Memory Composite Score
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.
Measured: Baseline to mean (Mo 6, Mo 12)
Volumetric Magnetic Resonance Imaging (MRI) of Hippocampus
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.
Measured: 12 Months
Volumetric Magnetic Resonance Imaging (MRI) of Prefrontal Composite Region
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.
Measured: 12 Months
Volumetric Magnetic Resonance Imaging (MRI) of AD Signature Composite Region
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.
Measured: 12 Months
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of Hippocampus
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.
Measured: Baseline to 12 Months
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of Prefrontal Composite Region
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.
Measured: Baseline to 12 Months
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of AD Signature Composite Region
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.
Measured: Baseline to 12 Months
Ratio of AD Biomarkers in Blood
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.
Measured: 12 Months
AD Biomarkers in CSF (ab42/ab40)
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.
Measured: 12 Months
AD Biomarkers in CSF (ab42/Tau)
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.
Measured: 12 Months
AD Biomarkers in CSF (ab42/P-tau)
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.
Measured: 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Sep 201619 Dec 2021

First posted27 Jun 2016 (estimated)
Study start13 Sep 2016
Primary completion17 Nov 2021
Study completion19 Dec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 296 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02814526
Sponsor's protocol ID: ADC-041-EX
Other IDs: U19AG010483-22
Acronym: EXERT
Status last verified: Feb 2023
First submitted: 2 Jun 2016
Last updated: 15 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: Data sharing is integral to the ADCS's mission to develop and execute innovative clinical trials focused on interventions that may prevent, delay, or treat the expression of Alzheimer's disease and related dementias. The ADCS is committed to sharing resources and tools, including data, biospecimens, trial designs, outcome and analysis measures following NIH guidelines. DATA SHARING: The ADCS Data and Sample Sharing Committee (DSSC) grants access to de-identified data to individuals who complete the request process and agree to the conditions in an ADCS/UCSD Data Use Agreement (DUA). After approval and receipt of the fully executed DUA, applicants are authorized to acquire data. Non-compliance with the DUA, including the requirement to provide requested updates will jeopardize further access to data.

Publications

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.
PubMed 20065132
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.
PubMed 18768414
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.
PubMed 17167157
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.
PubMed 20890449
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.
PubMed 12586857
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.
PubMed 18625967
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.
PubMed 18400101
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.
PubMed 40271887

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Mild Cognitive Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Therapeutic Effects of Exercise in Adults With Amnestic Mild Cognitive Impairment (MCI)
ClinicalTrials.gov ID: NCT02814526
Acronym / sponsor ID: EXERT / ADC-041-EX
Conditions: Mild Cognitive Impairment, Cognitive Decline, Memory Impairment
Keywords: exercise
Study type: Interventional
Recruitment status: Completed
Enrolment: 296 participants (actual)
Lead sponsor: Alzheimer's Disease Cooperative Study (ADCS)University, hospital or other
Collaborators: National Institute on Aging (NIA), Wake Forest University Health Sciences
Study start: 13 Sep 2016 (actual)
Primary completion: 17 Nov 2021 (actual)
Study completion: 19 Dec 2021 (actual)
First posted: 27 Jun 2016 (estimated)
Results: Posted 15 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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:

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Aerobic	Experimental	Behavioral: Aerobic exerciseModerate/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	Active comparator	Behavioral: Stretching/balance/range of motion exerciseThe 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.

Who may qualify

Ages: 65 to 89 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (20 listed)

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

Key exclusion criteria (24 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Aerobic exerciseModerate/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 .	Behavioural	Aerobic
Stretching/balance/range of motion exerciseThe 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.	Behavioural	Stretching/balance/range of motion

Primary outcome

ADAS-Cog-Exec Global Composite
Time frame: 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.

13 secondary outcomes

ADAS-Cog-Exec Global Composite in Subset Population
Time frame: Baseline to mean (Mo 6, Mo 12)
Executive Function Composite Score
Time frame: Baseline to mean (Mo 6, Mo 12)
Episodic Memory Composite Score
Time frame: Baseline to mean (Mo 6, Mo 12)
Volumetric Magnetic Resonance Imaging (MRI) of Hippocampus
Time frame: 12 Months
Volumetric Magnetic Resonance Imaging (MRI) of Prefrontal Composite Region
Time frame: 12 Months
Volumetric Magnetic Resonance Imaging (MRI) of AD Signature Composite Region
Time frame: 12 Months
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of Hippocampus
Time frame: Baseline to 12 Months
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of Prefrontal Composite Region
Time frame: Baseline to 12 Months
Arterial Spin Labeling (ASL) Magnetic Resonance Imaging (MRI) of AD Signature Composite Region
Time frame: Baseline to 12 Months
Ratio of AD Biomarkers in Blood
Time frame: 12 Months
AD Biomarkers in CSF (ab42/ab40)
Time frame: 12 Months
AD Biomarkers in CSF (ab42/Tau)
Time frame: 12 Months
AD Biomarkers in CSF (ab42/P-tau)
Time frame: 12 Months

Results and safety

Results posted to the registry on 15 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aerobic	148	115
Stretching/Balance/Range of Motion	148	118

Primary outcome: ADAS-Cog-Exec Global Composite

Time frame: Baseline to mean (Mo 6, Mo 12). Least squares mean (Standard Error). Unit: Change score

Measure	Aerobic n = 124	Stretching/Balance/Range of Motion n = 126
Value	-0.146 (0.063)	-0.068 (0.063)

Aerobic vs Stretching/Balance/Range of Motion: Mean Difference (Net): 0.078, p = 0.29, Regression, Linear

Population analysed: Modified Intent-to-Treat (mITT) Population: Includes all eligible participants who (1) began the exercise intervention (Intervention Session 1) and (2) completed at least one post-baseline assessment for the primary analysis at Month 6 or Month 12. All consented randomized participants are grouped according to the treatment assigned at randomization, regardless of any protocol violations.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data is collected from the time of consent through the 12 month supervised exercise period and through the following 6 month unsupervised exercise period.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aerobic	23 of 148 (15.5%)	148 of 148 (100%)	1 of 148
Stretching/Balance/Range of Motion	23 of 148 (15.5%)	148 of 148 (100%)	2 of 148

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20065132Baker 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.
Background: PubMed 18768414Lautenschlager 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.
Background: PubMed 17167157Colcombe 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.
Background: PubMed 20890449Voss 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.
Background: PubMed 12586857Colcombe 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.
Background: PubMed 18625967Burns 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.
Results publication: PubMed 18400101Nichol 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.
Derived from this study: PubMed 40271887Shadyab 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.
Individual participant dataSharing planned: Yes. Data sharing is integral to the ADCS's mission to develop and execute innovative clinical trials focused on interventions that may prevent, delay, or treat the expression of Alzheimer's disease and related dementias. The ADCS is committed to sharing resources and tools, including data, biospecimens, trial designs, outcome and analysis measures following NIH guidelines. DATA SHARING: The ADCS Data and Sample Sharing Committee (DSSC) grants access to de-identified data to individuals who complete the request process and agree to the conditions in an ADCS/UCSD Data Use Agreement (DUA). After approval and receipt of the fully executed DUA, applicants are authorized to acquire data. Non-compliance with the DUA, including the requirement to provide requested updates will jeopardize further access to data.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Howard Feldman, MDCM FRCP(C) principal investigator

Alzheimer's Disease Cooperative Study (ADCS)

14 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ADAS-Cog-Exec Global Composite (time frame: Baseline to mean (Mo 6, Mo 12)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02814526, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2023.