Adaptive Aerobic Exercise for Alzheimer's Disease

(SMART Trial)

Overseen By Kristi Spieleder, MS

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Arizona State University

Must not be taking: Antidepressants

Disqualifiers: Unstable depression, Unstable anxiety, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 6 months

216 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different types of aerobic exercise, including High-Intensity Interval Training (HIIT) and Moderate Intensity Continuous Training (MICT), may benefit older adults with mild cognitive issues, such as early Alzheimer's Disease. Researchers aim to determine if activities like cycling can enhance fitness, brain health, and memory. Participants will engage in exercise sessions and undergo various tests and brain scans to monitor progress over a year. Ideal candidates are those 65 or older with mild memory problems who can safely exercise and agree to regular health assessments. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on exercise and cognitive health.

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 prior data suggests that these exercise protocols are safe for older adults with mild cognitive impairment or Alzheimer's Disease?

Previous studies have shown that high-intensity interval training (HIIT) improves physical fitness and brain function in older adults. It is generally safe and well-tolerated, with some research noting improvements in quality of life. Similarly, combined aerobic resistance exercise (CARE) effectively boosts thinking and movement abilities. Studies in older adults indicate that this type of exercise is both safe and beneficial. Moderate-intensity continuous training (MICT) is also linked to increased brain size and better mental function. Research suggests that regular aerobic exercise, like MICT, can protect the brain with age and reduce the risk of mental decline. Overall, all three exercise approaches appear safe for older adults, with positive effects on both body and mind. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these exercise interventions for Alzheimer's disease because they explore how different types of physical activity can impact brain health. High-Intensity Interval Training (HIIT) and Moderate Intensity Continuous Training (MICT) stand out because they incorporate structured aerobic exercise, which may boost cognitive function by improving blood flow and reducing inflammation in the brain. Unlike standard drug treatments that primarily aim to manage symptoms, these exercise methods could provide a non-pharmacological way to slow disease progression. Moreover, the combination of aerobic and resistance exercises, as seen in the Combined Aerobic Resistance Exercise (CARE) approach, might offer a comprehensive benefit by enhancing both cardiovascular and muscular health, potentially leading to overall improved quality of life for those with Alzheimer's.

What evidence suggests that this trial's exercise treatments could be effective for Alzheimer's Disease?

Research has shown that aerobic exercise can benefit people with mild memory problems or early Alzheimer's disease. In this trial, participants may follow different exercise regimens. High-Intensity Interval Training (HIIT), one study arm, can enhance brain function and physical fitness in older adults and may protect the brain. Another arm, Combined Aerobic Resistance Exercise (CARE), has proven effective in improving thinking skills and physical health. Similarly, Moderate Intensity Continuous Training (MICT), another treatment arm, may help reduce symptoms and improve daily activities in people with Alzheimer's. These studies suggest that various types of aerobic exercise could benefit brain health and memory. ^{1 2 5 6 7}

Who Is on the Research Team?

Fang Yu, PhD

Principal Investigator

Arizona State University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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+

Banner Alzheimer's Institute

Collaborator

Trials

9

Recruited

3,000+

Published Research Related to This Trial

In a study of 42 inactive obese middle-aged men, both high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), as well as alternating between the two, led to a similar 15% increase in cardiovascular fitness (VO2max) after 16 weeks.

All exercise groups also experienced significant reductions in weight, body mass index (BMI), body fat percentage, and waist circumference, indicating that both training methods are effective for improving body composition without significant differences in blood markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating high-intensity interval training and continuous training is efficacious in improving cardiometabolic health in obese middle-aged men. Poon, ET., Siu, PM., Wongpipit, W., et al.[2022]

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]

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]

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]

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]

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]

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]

A 2-month aerobic training program showed that older men with moderate Alzheimer's disease (AD) can improve their cardiorespiratory fitness, while those with severe AD may not benefit as much, indicating variability in response to exercise.

The study suggests that a longer duration of aerobic training, such as 6 months, may be more effective for improving fitness in older adults with AD, highlighting the need for tailored exercise programs based on individual fitness levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerobic training for older men with Alzheimer's disease: individual examples of progression. Yu, F., Leon, AS., Bliss, D., et al.[2021]

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]

A review of 14 studies on exercise and Alzheimer's disease found that exercise can significantly improve daily functioning and performance in patients, enhancing their ability to carry out daily activities.

Exercise also positively impacts neuropsychiatric symptoms and various cognitive functions, including sustained attention and visual memory, suggesting it may be a valuable intervention for managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What are the Benefits of Exercise for Alzheimer's Disease? A Systematic Review of the Past 10 Years. Hernández, SS., Sandreschi, PF., da Silva, FC., et al.[2018]

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 6-month exercise program combining high intensity interval training (HIIT) and moderate intensity continuous training (MICT) showed similar improvements in cardiorespiratory fitness (CRF) and mental health markers (anxiety and depression) compared to a standard MICT program in stroke or TIA patients, with both exercise groups outperforming a control group.

Both exercise programs were well-accepted by participants, and the addition of HIIT was found to be safe, indicating that HIIT can be effectively integrated into rehabilitation for stroke patients without compromising safety or efficacy.

NCBI (Pubmed)

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. Lapointe, T., Houle, J., Sia, YT., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10000686/

The Effects of Aerobic and Resistance Exercises on ... The purpose of this study is to investigate the effect of exercise on the cognitive and physical functions in patients with Alzheimer's disease ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999323005919

Effectiveness of Combined Aerobic and Resistance ... Combined aerobic and resistance exercise effectively improves cognition, ameliorates metabolic health, enhances physical function, and increases physical HRQoL

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11631704/

A meta-analysis of the efficacy of physical exercise ... The results indicate that physical exercise can significantly improve the daily living abilities of AD patients, with resistance training or ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04848038

Study Details | NCT04848038 | Combined Exercise Trial The study will enroll 280 individuals, age 65 to 80 years without cognitive impairment, into a 26-week exercise intervention to test the combined and ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2807450

Effects of Exercise Alone or Combined With Cognitive ... Both aerobic exercise and resistance training have been demonstrated to improve cognition in older adults, although the benefits of combining ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12522579/

Precision exercise in older adults with early Alzheimer's ... Aerobic exercise is promising for preventing Alzheimer's disease (AD) and AD-related dementia (ADRD), but exercise trials have shown mixed ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1064748114005727

A 9-Week Aerobic and Strength Training Program ... This is the first study that provides evidence for the effectiveness of a combined aerobic and strength training program to improve cognitive and motor function ...