High-Velocity Resistance Training for Brain Blood Flow and Cognitive Function in Older Adults

Training the Aging Brain Through Speed: Examining Cerebrovascular Adaptations Associated With Motor-Cognitive Performance Following High-Velocity Resistance Training in Older Adults at Risk for AD/ADRD

The goal of this clinical trial is to learn whether a 12-week high-velocity resistance training program can improve brain blood flow and thinking skills in adults ages 60 to 79 who are at higher risk for Alzheimer's disease and related dementias. Researchers want to understand whether this type of exercise can improve how well the brain regulates blood flow during mental and physical tasks and whether those changes are linked to improvements in thinking ability. The main questions this study aims to answer are whether high-velocity resistance training improves thinking skills such as executive function and processing speed, and whether it improves how blood flow in the brain responds during cognitive testing, changes in blood pressure, and controlled breathing tasks. Participants will complete two study visits at the University of Illinois Chicago, one before the program begins and one after 12 weeks. During these visits, researchers will measure strength, muscle power, and thinking skills. Participants will also complete non-invasive testing to measure blood flow in the brain using ultrasound. During some tasks, participants will walk on a treadmill at a comfortable pace while completing thinking tests. They will wear small sensors to measure heart rate, blood pressure, and breathing. After the first visit, participants will be randomly assigned, like flipping a coin, to one of two groups. One group will take part in supervised resistance training three times per week for 12 weeks at the University of Illinois Chicago. Each session will last about 60 minutes and will be supervised by trained exercise professionals. The other group will continue their usual daily activities for 12 weeks and then return for follow-up testing. Participants in the comparison group will be offered the exercise program after they complete the final study visit. Researchers hope this study will improve understanding of how structured exercise may support brain health in older adults at risk for dementia and help guide future prevention strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: At Risk for Cognitive Decline; At Risk for AD-dementia, With Subjective Cognitive Decline
• Intervention / Treatment: Behavioral: High-Velocity Resistance Training

Detailed Description

This study is a single-site, randomized, parallel-group clinical trial designed to evaluate both behavioral efficacy and mechanistic target engagement of high-velocity resistance training (HVRT) in older adults at elevated risk for Alzheimer's disease and related dementias (AD/ADRD). The trial is structured as an early-stage efficacy study consistent with a Stage IIA framework, with emphasis on testing a hypothesized physiological mechanism linking exercise to cognitive outcomes. A growing body of research suggests that vascular dysfunction may contribute to cognitive decline and dementia risk. Altered cerebrovascular regulation, including impaired neurovascular coupling, reduced dynamic cerebral autoregulation, and diminished cerebrovascular reactivity to carbon dioxide, has been observed in older adults and in individuals with vascular risk factors. These physiological impairments may limit the brain's ability to appropriately regulate blood flow during cognitive and physical demands. Exercise interventions may improve vascular function; however, the specific effects of high-velocity resistance training on cerebrovascular regulatory mechanisms and their relationship to cognitive performance remain insufficiently characterized. High-velocity resistance training emphasizes rapid concentric muscle actions performed against moderate external loads. This training approach is designed to improve neuromuscular power, which declines with aging and is strongly associated with functional mobility. HVRT may provide distinct hemodynamic and neurovascular stimuli compared to traditional resistance training due to the speed of contraction and associated pressor responses. This study will test whether a 12-week supervised HVRT intervention produces measurable improvements in executive function, processing speed, and motor-cognitive performance, and whether such improvements are associated with changes in cerebrovascular regulation. Participants will be randomized in a 1:1 ratio to either the HVRT intervention or a waitlist control condition. The intervention consists of three supervised sessions per week for 12 weeks, using progressive loading phases spanning approximately 40 to 80 percent of one-repetition maximum. All training sessions are conducted in person under the supervision of trained exercise professionals following standardized operating procedures. The waitlist control group will maintain usual activities during the 12-week period and will be offered the exercise program after completing post-intervention testing. Cognitive and motor-cognitive performance will be assessed under both single-task (seated) and dual-task (treadmill walking) conditions to evaluate cognitive function under varying levels of physiological demand. Dual-task paradigms are included to probe real-world motor-cognitive integration and to assess whether exercise-related adaptations extend to functionally relevant conditions. Cerebrovascular regulation will be assessed non-invasively using transcranial Doppler ultrasound to measure cerebral artery blood flow velocity. Continuous electrocardiography, beat-to-beat blood pressure monitoring, and end-tidal carbon dioxide measurement will be recorded concurrently to permit integrated physiological modeling. Neurovascular coupling will be evaluated as the change in cerebral blood flow velocity during cognitive activation. Dynamic cerebral autoregulation will be assessed using oscillatory lower-body negative pressure protocols to induce controlled blood pressure fluctuations. Cerebrovascular reactivity will be assessed using a standardized hypercapnic rebreathing procedure to quantify the cerebral blood flow response to elevated carbon dioxide levels. Primary analyses will examine group-by-time interaction effects on cognitive performance. Secondary analyses will evaluate changes in neurovascular coupling, dynamic cerebral autoregulation, and cerebrovascular reactivity. Exploratory analyses will estimate whether changes in cerebrovascular regulation statistically mediate intervention-related improvements in cognitive outcomes and whether biological sex moderates these associations. These mechanistic analyses are intended to inform the design of future fully powered efficacy trials. This study will contribute to understanding whether a scalable, supervised resistance training intervention can engage cerebrovascular mechanisms linked to cognitive performance in older adults at elevated dementia risk. Findings may inform the development of targeted exercise-based strategies to support brain health in aging populations.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stacey E Aaron, PhD; Phone Number: 312-355-7220; Email: seaaron@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 60 to 79 years
• Able to walk on a treadmill at a comfortable, self-selected pace for at least 30 minutes with short breaks
• Has at least one vascular risk factor (such as high blood pressure or high cholesterol)
• Has a first-degree family history of dementia or self-reported concerns about memory or thinking
• Fluent in English
• Willing and able to provide written informed consent
• Cleared to participate in supervised resistance training based on physical activity screening and, if required, physician clearance

Exclusion Criteria:

• Diagnosis of Alzheimer disease, other dementia, stroke, Parkinson disease, multiple sclerosis, or another major neurological disorder
• Unstable cardiovascular disease (such as recent heart attack, unstable chest pain, or uncontrolled abnormal heart rhythm)
• Uncontrolled high blood pressure
• Major psychiatric illness that would interfere with participation
• Medical condition that makes moderate-to-high intensity resistance training unsafe
• Current participation in structured high-intensity resistance training
• Any medical condition that, in the opinion of the study investigator, would increase risk during participation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Velocity Resistance Training; Participants in this arm will complete a 12-week supervised high-velocity resistance training program. Sessions will occur three times per week and last approximately 60 minutes each. Exercises will include multi-joint upper- and lower-body movements performed at moderate loads, progressing from approximately 40 to 80 percent of one-repetition maximum over three phases. All sessions will be conducted in person and supervised by trained exercise professionals. Participants will also complete baseline and post-intervention cognitive and cerebrovascular assessments.	Behavioral: High-Velocity Resistance Training; This intervention consists of supervised resistance training emphasizing rapid concentric muscle contractions performed against moderate external loads. Participants will train three times per week for 12 weeks, with each session lasting approximately 60 minutes. The program includes progressive loading across three phases, beginning at approximately 40 to 50 percent of one-repetition maximum, progressing to 50 to 65 percent, and then to 65 to 80 percent. Exercises target major upper- and lower-body muscle groups using resistance equipment. All sessions are conducted in person under supervision of trained exercise professionals to ensure proper technique, safety monitoring, and progression.; Other Names: Resistance Training; Power Training
No Intervention: Waitlist Control (Usual Activity); Participants in this arm will maintain their usual daily activities for 12 weeks and will not receive structured exercise during the study period. They will complete the same baseline and post-intervention cognitive and cerebrovascular assessments as the intervention group. After completing post-intervention testing, participants will be offered the supervised resistance training program.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Executive Function Standard Score	Executive function will be assessed using standardized computerized cognitive tests from the National Institutes of Health Toolbox. Participants will first complete the tests in a seated single-task condition, followed by completion of the same tests during treadmill walking (dual-task condition). Age-adjusted standard scores will be used (mean = 100, standard deviation = 15; higher scores indicate better performance). Dual-task cost will be calculated as the percent difference between dual-task and seated performance using the formula: [(dual-task standard score - single-task standard score) / single-task standard score] × 100. The primary metric is the change in executive function dual-task cost (%) from baseline to 12 weeks.	Baseline and 12 weeks
Change in Processing Speed Standard Score	Processing speed will be assessed using standardized computerized cognitive tests from the National Institutes of Health Toolbox. Participants will first complete the tests in a seated single-task condition, followed by completion of the same tests during treadmill walking (dual-task condition). Age-adjusted standard scores will be used (mean = 100, standard deviation = 15; higher scores indicate better performance). Dual-task cost will be calculated as the percent difference between dual-task and seated performance using the formula: [(dual-task standard score - single-task standard score) / single-task standard score] × 100. The primary metric is the change in processing speed dual-task cost (%) from baseline to 12 weeks.	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Neurovascular Coupling	Neurovascular coupling will be assessed using transcranial Doppler ultrasound to measure cerebral artery blood flow velocity (cm/s). Neurovascular coupling is defined as the change in cerebral blood flow velocity during cognitive activation compared to resting baseline. The primary metric will be the task-related change in cerebral blood flow velocity expressed as absolute change (cm/s) and/or percent change (%). Greater task-related increases indicate improved neurovascular responsiveness.	Baseline and 12 weeks
Change in Dynamic Cerebral Autoregulation	Dynamic cerebral autoregulation will be assessed using transcranial Doppler ultrasound during controlled oscillatory lower-body negative pressure. Projection pursuit regression analysis will be applied to characterize the nonlinear relationship between arterial blood pressure and cerebral blood flow velocity. The primary autoregulatory metrics will include the active autoregulatory range (mmHg), defined as the arterial pressure range over which cerebral blood flow velocity remains relatively stable, as well as the slope of the active autoregulatory range, the rising slope, and the falling slope (all expressed in cm/s/mmHg). A wider active autoregulatory range and flatter slopes indicate more effective autoregulatory buffering capacity.	Baseline and 12 weeks
Change in Cerebrovascular Reactivity	Cerebrovascular reactivity will be assessed using transcranial Doppler ultrasound during a standardized carbon dioxide rebreathing protocol. Reactivity will be quantified as the slope of the cerebral blood flow velocity response to changes in end-tidal carbon dioxide. The primary metric will be expressed as cm/s/mmHg or percent change per mmHg. Steeper slopes indicate improved cerebrovascular responsiveness.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: February 23, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Prevention; Older adults; Resistance training; Executive function; Power training; Cerebrovascular function; Transcranial Doppler ultrasound; Cerebrovascular reactivity; Vascular cognitive impairment; Dual task walking; Processing speed; Dynamic cerebral autoregulation; Neurovascular coupling; High velocity resistance training; Cerebrovascular regulation; Cerebrovascular impairment; Motor cognitive performance; Alzheimer's disease risk; Alzheimer's disease and related dementia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Physical Conditioning, Human; Exercise; Resistance Training
• Other Study ID Numbers: 2026-0214; 5P30AG022849-22 (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