Exercise, Age-Related Memory Decline, And Hippocampal Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01329653
Recruitment Status : Active, not recruiting
First Posted : April 6, 2011
Last Update Posted : March 29, 2017
Information provided by (Responsible Party):
New York State Psychiatric Institute

Brief Summary:
The purpose of this study is to test the hypothesis that aerobic exercise leads increased cerebral blood volume in the dentate gyrus of the hippocampus in a sample of young and older adults.

Condition or disease Intervention/treatment Phase
Cognitive Deterioration Disorder of Aging Behavioral: aerobic training Behavioral: Wait list Not Applicable

Detailed Description:
In the US, increased length of life and reduced morbidity and mortality have resulted in a growing number of older adults, the demographic "time bomb" often referred to in discussions of public policy. According to the Census Bureau, the population aged 65 and over will double in size within the next 25 years. Moreover, these older adults will live healthier lives than their predecessors. While this increased length of a healthy life is an undeniable societal benefit, it brings with it a major societal problem: an epidemic of aging-related cognitive decline. The need to develop interventions to address this growing problem is urgent. Aging-related cognitive dysfunction is not diffuse; rather it targets selected brain areas, in particular the frontal lobes and the hippocampal formation. The separate but interconnected subregions of the hippocampus are differentially vulnerable to pathogenic mechanisms, including the normal aging process. A range of in vivo and post-mortem studies have converged on the dentate gyrus (DG) as the hippocampal subregion differentially targeted by the aging process. As with pathogenic processes, any intervention that improves brain function does so with regional selectivity. One such intervention is physical exercise, which has been shown to improve both frontal lobe and hippocampal function. Using a high-resolution variant of functional magnetic resonance imaging (fMRI), the investigators have demonstrated that aerobic training selectively benefitted DG function both humans and mice. In addition, improvement in DG function was associated with improved performance on a word list learning task but not in tasks conventionally thought to be frontal lobe dependent. The human part of the study had significant shortcomings, however: it was small (N = 11), lacked a control group, enrolled only young subjects (age 20-45 years), and employed only a limited neuropsychological testing battery. The overall goal of this proposal is to use the high-resolution variant of fMRI to test the hypothesis that aerobic training will induce improvements in DG function in a sample of younger (age 20-35) and older (50-65) adults, assigned randomly to an active training condition or wait list control group. The investigators will use more comprehensive neuropsychological testing to examine the relationship between changes in DG function and selected cognitive capacities. Taken together with the observation that normal aging differentially targets the DG, this research program will establish that physical exercise is an effective approach for ameliorating the insidious cognitive slide that occurs in aging. Thus, the potential significance of this application is substantial.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Exercise, Age-Related Memory Decline, And Hippocampal Function
Study Start Date : June 2011
Estimated Primary Completion Date : December 31, 2017
Estimated Study Completion Date : December 31, 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: aerobic training
12 weeks of aerobic training, 4X/week
Behavioral: aerobic training
12 weeks of aerobic training, 4X/week
Placebo Comparator: wait list control
wait list control condition, 12 weeks to parallel the active intervention group
Behavioral: Wait list
wait list control condition
Other Name: Wait list control

Primary Outcome Measures :
  1. dentate gyrus cerebral blood volume [ Time Frame: change from before (pre) to after (post) 12 weeks of training ]

Secondary Outcome Measures :
  1. cognitive function [ Time Frame: change from before (pre) to after (post) 12 weeks of training ]
    measures of memory, executive function, attention/processing speed, language, and general intelligence

  2. aerobic capacity [ Time Frame: change from before (pre) to after (post) 12 weeks of training ]
  3. cerebral blood flow [ Time Frame: change from before (pre) to after (post) 12 weeks of training ]
    arterial spin labeling fMRI

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Age 20-75 years
  2. English-speaking
  3. Ambulatory
  4. "Average" fitness as determined by ACSM's Guidelines for Exercise Testing and Prescription (for men, VO2max < 43 for age 20-39 years, < 38 for age 40-49 years, < 35 for age 50-59, < 31 for age 60-75; for women, < 36 for age < 30 years, < 34 for age 30-39 years, < 32 for age 40-49 years, <25 for age 50-59 years, < 24 for age 60-75 years
  5. BMI <35

Exclusion Criteria:

  1. Ischemic changes or abnormal resting cardiogram, abnormal blood pressure responses, or an significant ectopy during aerobic capacity testing
  2. Cardiovascular disease
  3. BMI > 35
  4. Uncontrolled high blood pressure (systolic blood pressure ≥ 140 mmHg; or diastolic blood pressure ≥ 90mmHg on two measures)
  5. Any condition for which aerobic training is counter-indicated, including persons with evidence or history of medical or orthopedic conditions which might make participation problematic.
  6. Current or recent (evidence of disease x 5 years) non-skin neoplastic disease or melanoma. Prostatic carcinoma will not be grounds for exclusion.
  7. Active hepatic disease (not a history of hepatitis) or primary renal disease requiring dialysis, primary untreated endocrine diseases, e.g., Cushing's disease or primary hypothalamic failure or insulin dependent diabetes (Type I or II). Welltreated hypothyroidism will not be excluded.
  8. History of chemotherapy
  9. HIV infection
  10. Pregnant or lactating (participation allowed 3 months after ceasing lactation).
  11. Medications that alter inflammation or autonomic nervous system activity
  12. Any history of psychosis or ECT
  13. Current or recent (past one year) Major Depressive Disorder, Bipolar Disorder
  14. Current or recent (within past 12 months) alcohol or substance abuse or dependence. Recent use (past month) of recreational drugs.
  15. Dementia Rating Scale (DRS) score less than 135. Medical History Interview
  16. Neurological Disorders Dementia Rating Scale
  17. Stroke Telephone screen
  18. Alzheimer's Disease Telephone screen
  19. Smoking Telephone screen
  20. Prior participation in another Dr. Sloan Exercise Study
  21. MRI Exclusion Criteria: Cardiac Pacemaker; Internal Pump; Insulin Pump; Tattoo; eyeliner; Wire Sutures; Internal Metal Objects; Metal Slivers in Eye; Prosthesis; Hearing Aid Implants; Neurostimulator; Metal Fragments; Brain Aneurysm Clips; Vascular Clips; Breast Expander; Vena Cava Filter; Heart Valve; Metal Stents; Asthma; Hay-Fever; Sickle Cell Disease; Kidney Disease; Machinist or ever worked with heavy metals Interview; Contraindication to gadolinium, including prior adverse reaction to gadolinium, past or current history of severe breathing difficulty that has been treated by a physician (e.g., asthma, COPD, etc.), and sickle cell disease. History of renal impairment or estimated glomerular filtration rate <30 L/min/1.73m2 is also exclusionary; Machinist or ever worked with heavy metals Interview; Have had more than one MRI scans with Gadolinium

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01329653

United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Principal Investigator: Richard P Sloan, PhD Columbia University

Publications of Results:
Responsible Party: New York State Psychiatric Institute Identifier: NCT01329653     History of Changes
Other Study ID Numbers: #6219/#7161R
AG035015 ( Other Identifier: CU )
First Posted: April 6, 2011    Key Record Dates
Last Update Posted: March 29, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We will share our data with other investigators upon request.

Keywords provided by New York State Psychiatric Institute:
cerebral blood volume

Additional relevant MeSH terms:
Cognition Disorders
Neurocognitive Disorders
Mental Disorders