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Exercise in Adults with Mild Memory Problems (EXERT)

Active, not recruiting

This study evaluates the effects of physical exercise on cognition, functional status, brain atrophy, 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- to high-intensity aerobic training program.

Minimum Age Maximum Age Gender Healthy Volunteers
65 Years 89 Years All No
September 13, 2016
November 2021

  • Mini-Mental State Exam score at least 24 for participants with 13 or more years of education or at least 22 for participants with 12 or fewer years of education
  • Clinical Dementia Rating of 0.5; impaired delayed verbal recall
  • Speaks English fluently
  • Seeing and hearing ability adequate for cognitive testing
  • At least 6 years of formal education or work history sufficient to exclude mental retardation
  • Study partner who knows participant well, has at least weekly contact, and is available to accompany participant to clinic visits
  • Sedentary or underactive, determined by responses to staff-administered survey
  • Willing and able to travel to YMCA four times per week for 18 months
  • Ability to safely participate in either intervention and complete the 400-meter Walk Test within 15 minutes without sitting or assistance
  • Plans to reside in the area for at least 18 months; willing to continue assigned exercise program if travelling out of the area for more than 1 week
  • Overall good general health, with no disease or planned surgery that could interfere with study participation
  • Modified Hachinski score of 4 or lower
  • Stable use of cholinesterase inhibitors, memantine (Namenda), vitamin E (up to 400 IU daily), estrogens, aspirin (81-300 mg daily), beta-blockers, or cholesterol-lowering agents for 12 weeks prior to screening is allowed
  • Stable use of antidepressants lacking significant anticholinergic side effects for 4 weeks prior to screening is allowed, as long as participant does not meet criteria for major depression currently or in the last 12 months
  • When applicable, willing to complete 4-week washout of psychoactive medications, including disallowed antidepressants, neuroleptics, chronic anxiolytics, or sedative hypnotics; willing to avoid these medications for the duration of the trial 

  • Significant neurological disease, other than MCI, including any form of dementia, Parkinson's 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 completion of the study
  • Contraindications for MRI studies, including claustrophobia, metal (ferromagnetic) implants, or cardiac pacemaker
  • Evidence of infection, infarction, or other clinically significant focal lesions, shown by MRI of brain at screening
  • History of major depression or bipolar disorder, psychotic features, agitation, or behavioral problems within the last 12 months; history of schizophrenia
  • History of alcohol or substance abuse or dependence within the past 2 years; currently consume more than three 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
  • 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 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 post treatment
  • Hemoglobin A1c greater than 7 
  • Clinically significant abnormalities in laboratory test results at screening
  • Current or past use of insulin to treat type 2 diabetes (other diabetes medications are acceptable if hemoglobin A1c is 7 or lower)
  • Current use of psychoactive medications, including tricyclic antidepressants, antipsychotics, mood-stabilizing psychotropic agents (such as 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 that benzodiazepines for treatment on an as-needed basis for insomnia or daily dosing of anxiolytics is permitted
  • Previous or current treatment involving active immunization against amyloid; previous treatment with investigational agents with anti-amyloid properties; passive immunization against amyloid within 12 months prior to screening and during trial
  • Treatment with other investigational agents within 3 months prior to screening and during trial
  • For lumbar puncture: current use of anticoagulants such as Coumadin or Plavix; current blood-clotting or bleeding disorder; significantly abnormal prothrombin time or partial thromboplastin time at screening; presence of physical distortions due to spinal surgery, severe degenerative joint disease or deformity; obesity that could interfere with cerebrospinal fluid collection

Participants will be randomly assigned to either the stretching-balance-range of motion exercise group or the aerobic exercise group. The first group will exercise at or below 35 percent of maximum heart rate for 30 minutes, with an additional 10 minutes for warmup and 5 minutes for cool-down, four times per week, for 12 months. The second group will exercise at 70 percent to 80 percent of maximum heart rate for 30 minutes, with an additional 10 minutes for warmup and 5 minutes for cool-down, four times per week, for 12 months. All participants will be supervised twice per week by a study-certified trainer at a participating YMCA.

For more information about the EXERT study, contact the Alzheimer's Disease Cooperative Study at or visit

Name City State Zip Status Primary Contact
University of California, Irvine
Irvine California 92697

VAPAHCS / Stanford University School of Medicine
Palo Alto California 94304

Yale University School of Medicine
New Haven Connecticut 06510

Emory University
Atlanta Georgia 30329

Great Lakes Clinical Trials (Andersonville)
Chicago Illinois 60640

University of Kansas Medical Center
Kansas City Kansas 66205

University of Kentucky
Lexington Kentucky 40536

Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas Nevada 89106

New York University Medical Center
New York New York 10016

Mount Sinai School of Medicine
New York New York 10029

Duke University
Durham North Carolina 27705

Wake Forest University Health Sciences
Winston-Salem North Carolina 27157

University of North Texas Health Science Center
Fort Worth Texas 76107

University of Wisconsin
Madison Wisconsin 53792

Alzheimer's Disease Cooperative Study (ADCS)

  • National Institute on Aging (NIA)
  • Wake Forest University

Name Phone Email
Genny Matthews 858-246-1318


Therapeutic Effects of Exercise in Adults With Amnestic Mild Cognitive Impairment