Aging Brain Structure and Memory in Response to Exercise

Mechanical Integrity of Memory Systems in Mild Cognitive Impairment

This study will measure brain structure through its mechanical properties, assessed with magnetic resonance elastography, and determine whether it improves with aerobic exercise in older adults with low memory abilities. Additionally, this study will determine if memory abilities improve with exercise and if they are related to brain structure. Overall, this project has the potential to identify how brain health is impacted by exercise in older adults.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Behavioral: Aerobic exercise; Behavioral: Stretching

Detailed Description

Mechanical properties of the human brain, measured with magnetic resonance elastography (MRE), reflect the health of brain tissue. Our previous research has shown that these mechanical properties of the hippocampus are highly sensitive to memory function in young adults. Based on these findings, we believe that these mechanical properties may be strong indicators of memory health in older adults and populations experiencing decline in memory function (i.e. mild cognitive impairment, MCI). Further, our results indicate these properties and associated functions are positively impacted by fitness and exercise training, thus making them potentially ideal markers for brain health in assessing rehabilitation.

The objective of this research is to examine these properties in older adults with and without MCI. We will do the following: (1) determine if there are differences in mechanical properties of memory systems in older adults with and without MCI; (2) establish structure-function relationships between mechanical properties and memory performance in the older adult population; and (3) determine if both mechanical properties and memory performance are impacted by cardiovascular health, both through cross-sectional assessment of aerobic fitness and longitudinal response to exercise training.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • University of Delaware

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Cognitive function scores consistent with amnestic mild cognitive impairment based on pre-screening evaluation
• age 60-90 years
• MMSE score >24 at time of initial consent

Exclusion Criteria:

• major psychiatric disorder (e.g. schizophrenia, bipolar disorder, major depression within past two years)
• neurological or autoimmune conditions affecting cognition (e.g. Parkinson's disease, epilepsy, multiple sclerosis, head trauma with loss of consciousness greater than 30 min, large vessel infarct)
• other systemic medical illnesses (e.g. cardiovascular disease, cancer, renal failure, diabetes, chronic obstructive pulmonary disease, liver diseases, hypertension)
• current medication use likely to affect CNS functions (e.g. long active benzodiazepines)
• failed outcome on the baseline graded exercise test
• hypertension (systolic 130+ mmHg OR diastolic 80+ mmHg) from baseline blood pressure measurement
• claustrophobia, metal implants, pacemaker or other factors affecting feasibility and/or safety of MRI scanning
• concussion within last 2 years and more than 3 lifetime concussions
• current smoking (including marijuana) within the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic exercise; Exercise training	Behavioral: Aerobic exercise; Participants will complete 12 weeks of supervised aerobic exercise, 3 times per week, on a treadmill or stationary bicycle
Active Comparator: Stretching; Control	Behavioral: Stretching; Participants will complete 12 weeks of supervised stretching, 3 times per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain mechanical properties	Investigators are assessing change in brain structure through mechanical properties in response to exercise from baseline to the end of the 12 week program. An MRI scan with magnetic resonance elastography (MRE) will be used to measure properties of brain regions important to memory (e.g. hippocampus).	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in relational memory performance	Behavioral memory test will be used to assess relational memory through accuracy on a spatial reconstruction task.	Baseline, 12 weeks
Change in cardiorespiratory fitness	Graded exercise test will measure cardiorespiratory fitness through volume of oxygen uptake (VO2)	Baseline, 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain morphometry	MRI will be used to measure brain morphometry, i.e. volume	Baseline, 12 weeks
Change in brain function	MRI will be used to measure brain function, i.e. functional connectivity	Baseline, 12 weeks
Change in brain white matter integrity	Diffusion MRI will be used to measure integrity of white matter tracts	Baseline, 12 weeks
Change in cognitive function	NIH Toolbox will be used to assess cognitive function across several domains	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: University of Delaware
• Collaborators: National Institute on Aging (NIA); Christiana Care Health Services; University of Illinois at Urbana-Champaign
• Investigators: Principal Investigator: Curtis L Johnson, PhD, University of Delaware

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): March 31, 2024

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (Actual): February 26, 2019

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Exercise; Memory; Brain
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 1256861; R01AG058853 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No