Working Memory and Physical Exercise Training in Patients With Mild Cognitive Impairment

May 7, 2026 updated by: Linda Chang, University of Maryland, Baltimore

Adaptive Working Memory and Physical Exercise Training to Improve Brain and Mitochondrial Function in MCI

The prevalence of dementia will double in the next three decades in the U.S.; effective treatment or prevention for dementia is urgently needed. The current exploratory project aims to evaluate and understand how the brain and cognition may improve after a 12-week intervention that combines brain training and aerobic exercise training to improve brain function, both in those with mild cognitive impairment (some with possible prodromal Alzheimer's disease) and with healthy aging. Findings from this pilot project will guide and refine the development of a future larger clinical trial that aligns with the goals of the National Alzheimer's Plan of Action (NAPA), especially regarding "Prevent and Effectively Treat Alzheimer's Disease (AD) by 2025.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Adult men and women of all races and ethnicities who are 50-80 years of age will be eligible.
  • Only sedentary adults will be eligible (engaging in structured activity for exercise <3x/week) for Progressive aerobic exercise or Combined training
  • Ability to use, and accessibility to, an iPad or computer is required for the Adaptive cognitive training and Combined training.
  • Fluent in English.
  • The diagnosis of MCI will first be confirmed at the screening evaluation using the clinical dementia rating (CDR) scale and the Montreal Cognitive Assessment (MoCA). We will also evaluate their ADL using instrumental activities of daily living (IADL) to ensure they have preserved independence in functional abilities despite the cognitive deficits. The primary caregivers will be interviewed (either in person or by phone) for the participants' IADL to corroborate the independent functional status.

Exclusion Criteria:

  • Does not have access to a computer or internet to perform the Cogmed® training AND is unwilling to come to the lab for the training.
  • Unable to undergo an MRI investigation based on claustrophobia or metal foreign bodies.
  • Symptomatic heart disease, Coronary artery disease, congestive heart failure, uncontrolled hypertension, uncontrolled diabetes (HbA1c>10%), significant cardiovascular disorders (on EKG and graded exercise test) that would prevent the participant from the exercise training; neurologic, musculoskeletal, or other condition that limits the subject's ability to complete study physical assessments.
  • Estimated verbal Intelligence Quotient (IQ) below 70 (based on the Wechsler Test of Adult Reading) which would invalidate the informed consent process for the study.
  • Self-reported moderate to severe substance use disorder(s) (e.g., self-reported intake >3 oz liquor, or three 4 oz glasses of wine, or three 12 oz cans of beer per day or illicit drug use).
  • Severe chronic or acute medical or other (non-MCI) neuropsychiatric conditions that might confound the cognitive or brain imaging measures (e.g., liver function tests >2.5 normal range or evidence for renal failure).
  • Body mass index >40 kg/m2.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aerobic Exercise
Progressive aerobic exercise 3x/week for 12 weeks.
Behavioral: Progressive aerobic exercise
Progressive aerobic exercise
Experimental: Cognitive Training
Adaptive cognitive training on Cogmed 5x/week for a total of 25 sessions in 5-8 weeks.
Behavioral: Adaptive cognitive training
Adaptive cognitive training
Experimental: Combined Cognitive and Aerobic Exercise
Combined progressive aerobic exercise 3x/week for 12 weeks and adaptive cognitive training on Cogmed 5x/week for a total of 25 sessions in 5-8 weeks simultaneously.
Behavioral: Combined
Combine adaptive cognitive and progressive aerobic exercise training

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Brain structure measures
Time Frame: At baseline and at 4 weeks after the corresponding training program.
Changes in brain volume measures from T1-weighted images (volumes in mm3)
At baseline and at 4 weeks after the corresponding training program.
Changes in brain cortical thickness measures
Time Frame: At baseline and at 4 weeks after the corresponding training program.
Changes in brain cortical thickness measures from T1-weighted images (thickness measures in mm)
At baseline and at 4 weeks after the corresponding training program.
Changes in Brain microstructure measures
Time Frame: At baseline and at 4 weeks after the corresponding training program.
Changes in brain measures of diffused tensor imaging (diffusion coefficient in mm²/s)
At baseline and at 4 weeks after the corresponding training program.
Changes in Brain blood flow from Arterial spin labeling magnetic resonance imaging (ASL-MRI) in milliliters/100 g/minutes
Time Frame: At baseline and at 4 weeks after the corresponding training program.
Changes in Brain blood flow from Arterial spin labeling magnetic resonance imaging (ASL-MRI) in milliliters/ 100 g/ minutes
At baseline and at 4 weeks after the corresponding training program.
Changes in Brain Activation on functional MRI
Time Frame: At baseline and at 4 weeks after the corresponding training program.
Changes in functional MRI from blood oxygen level dependence (BOLD) contrast on fMRI (in percentage change)
At baseline and at 4 weeks after the corresponding training program.
Changes in cognitive performance, emotions, and motor function based on NIH toolbox
Time Frame: At baseline and at 4 weeks after the corresponding training program.
Changes in cognitive performance, emotions, and motor function in raw scores measured by the NIH Toolbox® (reports will be generated as T scores, with higher T scores indicating better outcomes)
At baseline and at 4 weeks after the corresponding training program.
Changes in executive function using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)
Time Frame: At baseline and at 4 weeks after the corresponding training program.
Changes in executive function using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) (reports will be generated as T scores, with lower T scores indicating better outcomes and T scores higher than 65 indicating significant impairments in the executive function)
At baseline and at 4 weeks after the corresponding training program.
Changes in Blood Bioenergetic Markers
Time Frame: At baseline and at 4 weeks after the corresponding training program.

Platelet mitochondrial respiration (OCR) and extracellular acidification rates (ECAR) will be evaluated to assess bioenergetic profiles in platelets isolated from whole blood of fasted participants. OCR will be measured using a Seahorse model XFe96 machine as the high throughput platform. Measurements of OCR/ECAR will be performed with the following modifications. Platelets will be isolated from whole blood with a Beckman Allegra model X-30R centrifuge.

Platelets will be counted using a Nexcelom Bioscience Cellometer (Lawrence, MA) using Calcein acetoxymethyl (AM) ester dye to enable the seeding of 10,000,000 platelets per well.
At baseline and at 4 weeks after the corresponding training program.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
VO2peak
Time Frame: At baseline and within one week after the corresponding training program.
VO2peak will be used as the primary measure of aerobic capacity. Subjects will be asked to exercise to voluntary exhaustion during a treadmill test using a modified Bruce protocol. Oxygen (O2) consumption, carbon dioxide (CO2) production, and minute ventilation will be measured breath-by-breath using a metabolic cart and the average of the final two 20 second values of O2 consumption are VO2peak.
At baseline and within one week after the corresponding training program.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2024

Primary Completion (Estimated)

December 16, 2026

Study Completion (Estimated)

August 7, 2027

Study Registration Dates

First Submitted

July 3, 2023

First Submitted That Met QC Criteria

July 12, 2023

First Posted (Actual)

July 17, 2023

Study Record Updates

Last Update Posted (Actual)

May 12, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00105789

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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