Adaptive Aerobic Exercise for Alzheimer's Disease

(SMART Trial)

Overseen by Fang Yu, PhD

Age: 65+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Arizona State University

Must not be taking: Antidepressants

Disqualifiers: Unstable depression, Unstable anxiety, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to test 6 months of aerobic exercise in older adults who are 65 years or older and have mild cognitive impairment (MCI) or probable/possible mild Alzheimer's Disease. The main questions it aims to answer are: * test the effects of aerobic exercise on aerobic fitness, white matter hyperintensity (WMH) volume, and patient-centered outcomes; * identify the best exercise to improve aerobic fitness and reduce non-responses over 6 months; and * examines the mechanisms of aerobic exercise's action on memory in older adults with early AD. Participants will receive 6 months of supervised exercise, undergo cognitive data collection and exercise testing 5 times over a year span, have an MRI brain scan 3 times over a one-year span, and have monthly follow-up discussions on health and wellness.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on two or more anti-depression medications or have poorly managed depression or anxiety, you may not be eligible to participate.

What data supports the effectiveness of the treatment Adaptive Aerobic Exercise for Alzheimer's Disease?

Research shows that aerobic exercise can improve physical fitness and mood in Alzheimer's patients, and may enhance cognitive functions like attention and memory. Some studies suggest that combining aerobic exercise with resistance training can lead to significant fitness gains and improve quality of life for those with Alzheimer's disease. ^{1 2 3 4 5}

Is adaptive aerobic exercise, like HIIT and MICT, safe for humans?

Research shows that both high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) are generally safe for humans, including those with conditions like metabolic syndrome and cardiovascular diseases. These exercises have been studied for their safety and effectiveness in improving fitness and health, with no major safety concerns reported. ^{6 7 8 9 10}

How does the treatment of aerobic exercise differ from other treatments for Alzheimer's disease?

This treatment is unique because it focuses on improving cardiorespiratory fitness through aerobic exercise, such as High-Intensity Interval Training (HIIT) and Moderate Intensity Continuous Training (MICT), which may help maintain physical fitness and function in Alzheimer's patients. Unlike standard drug treatments, this approach emphasizes physical activity to potentially enhance brain health and fitness. ^{1 3 11 12 13}

Research Team

Fang Yu, PhD

Principal Investigator

Arizona State University

Eligibility Criteria

This trial is for adults aged 65 or older with mild cognitive impairment (MCI) or early Alzheimer's Disease. They need medical clearance, a study partner who knows their memory and daily living abilities, and must be living in the community. People can't join if they have certain heart conditions, are on multiple depression medications, do other cognition interventions, exercise heavily already, or have unmanaged anxiety.

Inclusion Criteria

Have a qualified study partner

I am 65 years old or older.

Consent to participant

Exclusion Criteria

You have a heart condition found during a specific test for measuring your body's ability to use oxygen.

You have been doing challenging exercise for at least 150 minutes per week in the last 6 months.

I have tried at least 2 antidepressants or my depression is not well-controlled.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 6 months of supervised aerobic exercise, with exercise testing and cognitive data collection occurring 5 times over a year.

6 months

5 visits (in-person) over a year

Follow-up

Participants have monthly follow-up discussions on health and wellness, and are monitored for safety and effectiveness after treatment.

6 months

Monthly discussions (virtual or in-person)

Extension

Participants may continue with alternative exercise interventions such as HIIT or CARE if identified as non-responders to MICT.

3 months

Treatment Details

Interventions

• Chair-based Stretch (Behavioural Intervention)
• Combined Aerobic Resistance Exercise (CARE) (Behavioural Intervention)
• High-Intensity Interval Training (HIIT) (Behavioural Intervention)
• Moderate Intensity Continuous Training (MICT) (Behavioural Intervention)

Trial Overview The trial tests four types of exercises: Moderate Intensity Continuous Training (MICT), Chair-based Stretching, High-Intensity Interval Training (HIIT), and Combined Aerobic Resistance Exercise (CARE). It aims to see which improves aerobic fitness and memory over six months in older adults with MCI or mild Alzheimer's.

Participant Groups

Group I: Moderate Intensity Continuous Training (MICT) Experimental Treatment 1 Intervention

Cycling on recumbent stationary cycle at moderate intensity for 30-50 minutes, 3 times per week for 3-6 months

Group II: High-Intensity Interval Training (HIIT) Active Control 1 Intervention

MICT for 3 months, and then cycling on recumbent stationary cycle at alternate high and moderate intensity for 40 minutes, 3 times per week for 3 months.

Group III: Combined Aerobic Resistance Exercise (CARE) Active Control 1 Intervention

MICT for 3 months, and then cycling on recumbent stationary cycle at moderate intensity for 30 minutes, followed by 20-minute strength-building exercise, 3 times per week for 3 months.

Group IV: Chair-based Stretch Placebo Group 1 Intervention

Stretching at low intensity for 30-50 minutes, 3 times per week for 6 months

Who Is Running the Clinical Trial?

Arizona State University

Lead Sponsor

Trials

311

Recruited

109,000+

Mark McKenna

Arizona State University

Chief Executive Officer

Bachelor’s degree in marketing from Arizona State University, MBA from Azusa Pacific University

Cedric O’Gorman

Arizona State University

Chief Medical Officer since 2023

MD from Harvard Medical School

Banner Alzheimer's Institute

Collaborator

Trials

9

Recruited

3,000+

Findings from Research

After 9 weeks of training, both continuous aerobic training (CAT) and interval aerobic training (IAT) significantly improved aerobic fitness and functional capacities in seniors with Alzheimer's disease, compared to a control group.

While neither training method changed plasma BDNF levels or cognitive performance, CAT specifically improved quality of life for participants, indicating potential benefits beyond just physical fitness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 9 weeks continuous vs. interval aerobic training on plasma BDNF levels, aerobic fitness, cognitive capacity and quality of life among seniors with mild to moderate Alzheimer's disease: a randomized controlled trial. Enette, L., Vogel, T., Merle, S., et al.[2022]

In a study involving 51 patients with mild to moderate Alzheimer's disease, 16 weeks of moderate-to-high intensity aerobic exercise did not lead to consistent improvements in overall or regional cerebral blood flow.

The results suggest that this duration and intensity of exercise may not be enough to significantly impact cerebral blood flow in Alzheimer's patients, indicating a need for further research on exercise interventions in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of physical exercise on cerebral blood flow in Alzheimer's disease. van der Kleij, LA., Petersen, ET., Siebner, HR., et al.[2021]

A longitudinal study involving 24 individuals with early-stage Alzheimer's disease showed that participation in a structured exercise program significantly improved physical fitness, including aerobic capacity and strength, with highly significant gains in the six-minute walk test (p < .001).

The program also positively impacted mood and slowed cognitive decline, demonstrating that exercise combined with cognitive and social stimulation can provide meaningful benefits for individuals with Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Student-led exercise sessions yield significant fitness gains for Alzheimer's patients. Arkin, SM.[2022]

This study will evaluate the effectiveness of high-intensity interval training (HIIT) compared to moderate-intensity continuous training (MICT) in improving aerobic capacity in dogs, involving 30 dogs over a 12-week training period.

The research aims to measure various physiological parameters, including maximal speed and lactate threshold, to determine if HIIT provides superior benefits in enhancing physical performance in dogs compared to MICT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of high-intensity interval training compared with moderate-intensity continuous training on maximal aerobic potency in dogs: Trial protocol for a randomised controlled clinical study. Orozco, SC., Arias, MP., Carvajal, PA., et al.[2023]

High-intensity, low-volume interval training (HIIT-low volume) and moderate-intensity continuous aerobic training (MICT) are both safe for adults with metabolic syndrome, with no serious adverse reactions reported during a 12-week supervised exercise program involving 60 participants.

While both training methods had similar rates of musculoskeletal events, HIIT-low volume was associated with a higher incidence of cardiovascular events, suggesting caution for individuals with specific health concerns, such as venous insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of High-Intensity, Low-Volume Interval Training or Continuous Aerobic Training in Adults With Metabolic Syndrome. Gallo-Villegas, J., Restrepo, D., Pérez, L., et al.[2023]

High-intensity interval training (HIIT) can lead to equal or greater improvements in aerobic capacity compared to traditional moderate-intensity continuous training (MICT), while also positively affecting body composition, glucose metabolism, blood pressure, and quality of life.

HIIT offers a significant time advantage, allowing individuals to achieve the same energy expenditure in a shorter duration, making it a practical option for both healthy adults and those with cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salutary effects of high-intensity interval training in persons with elevated cardiovascular risk. Fleg, JL.[2018]

A 6-month moderate intensity cycling program improved cardiorespiratory fitness in 8 participants with Alzheimer's disease, as indicated by a significant reduction in heart rate during exercise tests.

However, the study did not find significant changes in lower extremity function or overall physical performance, suggesting that while aerobic exercise can enhance fitness, its effects on physical functioning may need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintaining physical fitness and function in Alzheimer's disease: a pilot study. Yu, F., Savik, K., Wyman, JF., et al.[2021]

A 16-week supervised aerobic exercise program for 200 patients with mild Alzheimer's disease did not show significant improvements in overall cognitive performance or quality of life compared to a control group.

However, the exercise program significantly reduced neuropsychiatric symptoms and showed potential cognitive benefits in patients who adhered closely to the exercise regimen, indicating that regular, intense exercise may help improve certain aspects of cognitive function in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial. Hoffmann, K., Sobol, NA., Frederiksen, KS., et al.[2022]

A 6-month cycling aerobic exercise program significantly improved cardiorespiratory fitness in older adults with mild-to-moderate Alzheimer's dementia, as indicated by an increase in peak oxygen consumption by 1.28 ml/kg/min.

The study highlighted the importance of exercise dose, showing a strong correlation (r=0.60) between the amount of aerobic exercise and improvements in peak oxygen consumption, suggesting that tailored exercise programs can enhance fitness outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Dose and Aerobic Fitness Response in Alzheimer's Dementia: Findings from the FIT-AD Trial. Salisbury, D., Mathiason, MA., Yu, F.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Aerobic training for older men with Alzheimer's disease: individual examples of progression. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Effect of 9 weeks continuous vs. interval aerobic training on plasma BDNF levels, aerobic fitness, cognitive capacity and quality of life among seniors with mild to moderate Alzheimer's disease: a randomized controlled trial. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of physical exercise on cerebral blood flow in Alzheimer's disease. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

What are the Benefits of Exercise for Alzheimer's Disease? A Systematic Review of the Past 10 Years. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Student-led exercise sessions yield significant fitness gains for Alzheimer's patients. [2022]

6. Singapore pubmed.ncbi.nlm.nih.gov

Alternating high-intensity interval training and continuous training is efficacious in improving cardiometabolic health in obese middle-aged men. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of high-intensity interval training compared with moderate-intensity continuous training on maximal aerobic potency in dogs: Trial protocol for a randomised controlled clinical study. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Addition of high-intensity interval training to a moderate intensity continuous training cardiovascular rehabilitation program after ischemic cerebrovascular disease: A randomized controlled trial. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Safety of High-Intensity, Low-Volume Interval Training or Continuous Aerobic Training in Adults With Metabolic Syndrome. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Salutary effects of high-intensity interval training in persons with elevated cardiovascular risk. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Maintaining physical fitness and function in Alzheimer's disease: a pilot study. [2021]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

Exercise Dose and Aerobic Fitness Response in Alzheimer's Dementia: Findings from the FIT-AD Trial. [2022]