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.

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.

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