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NCT Number: NCT05948930

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

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.

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Key information

Age range

50 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location status: Recruiting

Location contact

Huajun Liang, MBBS, PhD

CONTACT

[email protected]

410-706-1031

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Progressive aerobic exercise

Behavioral

Progressive aerobic exercise

Adaptive cognitive training

Behavioral

Adaptive cognitive training

Combined

Behavioral

Combine adaptive cognitive and progressive aerobic exercise training

Primary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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

  5. 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)

  6. 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)

  7. 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)

  8. 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.

Secondary outcomes

  1. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Linda Chang, M.D., M.S.

CONTACT

[email protected]

410 706 1036

Sponsors and collaborators

Lead sponsor

University of Maryland, Baltimore

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Jul 17, 2023
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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