Exercise for Improved Cognition and Cardiometabolic Health

Recruiting at 3 trial locations

Overseen By Steven K Malin, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Weight suppressants, Heart medications

Disqualifiers: Smoking, Hypertension, Metabolic disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically those for weight suppression and those that affect heart rate and rhythm. If you are on these medications, you would need to discontinue them to participate.

What data supports the effectiveness of the treatment Exercise, Physical Activity, Workout, Fitness Training for improved cognition and cardiometabolic health?

Research shows that regular exercise improves heart health, reduces risk factors for heart disease, and enhances overall quality of life. It also helps control weight, lowers blood pressure, and improves cholesterol levels, which are important for cardiometabolic health. ^{1 2 3 4 5}

Is exercise generally safe for humans?

Exercise is generally safe for humans, but there can be some risks, especially for people who are not used to physical activity or have existing health issues. Most adverse events are minor, like muscle injuries, and serious problems are rare. It's important to start slowly and gradually increase intensity to minimize risks. ^{6 7 8 9 10}

How does exercise as a treatment for cognition and cardiometabolic health differ from other treatments?

Exercise is unique because it improves cognition and cardiometabolic health by enhancing brain function and energy metabolism, and it does so without the need for medication. It works by increasing brain-derived neurotrophic factor, which supports brain health and plasticity, and it can be combined with dietary changes for even greater benefits. ^{11 12 13 14 15}

What is the purpose of this trial?

Dementia is a leading cause of death in the United States among aging adults. Brain insulin resistance has emerged as a pathologic factor affecting memory, executive function as well as systemic glucose control. Regular aerobic exercise decreases Alzheimer's Disease (AD) risk, in part, through changes in brain structure and function. However, there is limited data available on how exercise impacts brain insulin resistance in aging. This study will test the effect of acute exercise on brain insulin sensitivity in middle-aged to older adults. The study will also examine cognition and cardiometabolic health in relation to brain insulin sensitivity.

Research Team

Steven K Malin, PhD

Principal Investigator

Rutgers University - New Brunswick

Eligibility Criteria

This trial is for men and women aged 40-80 who are not very active (less than 150 minutes of exercise per week), have a BMI between 25 and 45, but aren't pregnant or nursing. It's not for those with serious health issues, recent smokers, or people on certain medications that affect weight or heart rate.

Inclusion Criteria

Your body mass index is between 25 and 45 kg/m2.

I am between 40 and 80 years old.

You do not engage in at least 150 minutes of moderate to high-intensity exercise per week.

Exclusion Criteria

You have had a significant weight change of more than 2 kilograms in the past 3 months.

You have a history of serious health conditions that could affect the study results or your safety.

I am currently on medication that affects my heart rate or rhythm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including MRI arterial spin labeling and cognitive testing

1 week

1 visit (in-person)

Intervention

Participants either rest or exercise at medium to hard intensity for 1 hour

1 week

1 visit (in-person)

Follow-up

Participants are monitored for changes in brain insulin sensitivity, cognition, and cardiometabolic health

1 week

1 visit (in-person)

Treatment Details

Interventions

• Exercise

Trial Overview The study investigates how a single session of exercise affects brain insulin sensitivity in middle-aged to older adults. It also looks at the relationship between this sensitivity, cognition, and overall cardiometabolic health.

Participant Groups

Group I: Exercise Experimental Treatment 1 Intervention

Individuals will exercise for at medium to hard intensity for 1 hour.

Group II: Rest Active Control 1 Intervention

Individuals will rest for about 1 hour in the seated position to mimic time exercising.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Findings from Research

Regular exercise significantly increases markers of exercise capacity, such as VO2max and ventilatory threshold (VT), which can enhance overall quality of life, especially for patients with health limitations.

Exercise serves as a positive health recommendation that not only improves physical fitness but may also indirectly encourage patients to adopt healthier behaviors, contrasting with traditional negative health advice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity and exercise training prescriptions for patients. Foster, C., Cadwell, K., Crenshaw, B., et al.[2019]

Regular exercise significantly benefits patients with heart disease by improving exercise tolerance, controlling risk factors, and potentially influencing the progression of coronary artery disease.

Patients should follow physician-guided exercise plans that include dynamic endurance activities and moderate-intensity circuit weight training, with a recommended duration of 2 to 3 hours per week, while high-risk patients should exercise at lower intensities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Heart patient and sports]. Niederhauser, HU.[2008]

Regular physical activity significantly reduces cardiovascular risk and mortality, with even low levels of exercise providing substantial health benefits for individuals, including those at high risk for cardiovascular events.

While exercise is generally safe, it can temporarily increase the risk of cardiovascular events during acute physical activity; however, these events are rare and can be mitigated through proper screening programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise: friend or foe? Dangardt, FJ., McKenna, WJ., Lüscher, TF., et al.[2022]

Regular mild aerobic exercise is linked to a lower risk of developing coronary artery disease and can improve survival rates in patients already diagnosed with the condition.

Exercise has multiple health benefits, including lowering blood pressure, improving insulin resistance, aiding weight loss, and positively affecting cholesterol levels, making it a valuable part of managing atherosclerotic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Exercise therapy of atherosclerosis]. Mori, T., Arakawa, K.[2011]

Regular physical activity significantly improves cardiovascular health, with effects comparable to traditional risk factors like smoking and high cholesterol, especially when engaging in intensive activities that exceed 6 METs.

Increasing cardiorespiratory fitness by just 1 MET can reduce cardiovascular risk by about 20%, and while exercise can pose a risk of sudden cardiac death, this risk is greatly mitigated by consistent training, making the overall benefits of exercise very favorable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiorespiratory fitness. Importance of sports for health]. Schmermund, A.[2006]

In a randomized controlled trial involving 209 elderly participants (average age 80), a home-based exercise program was found to be generally safe, with 151 adverse events reported, affecting 47% of participants.

Despite the program's safety, 14% of the adverse events were serious, highlighting that high levels of pre-existing morbidity in this population can pose challenges to maintaining consistent exercise participation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in mobility-limited and chronically ill elderly adults participating in an exercise intervention study supported by general practitioner practices. Hinrichs, T., Bücker, B., Wilm, S., et al.[2015]

In a 1.5-year study involving 274 male veterans with cardiovascular disease risk factors, only one serious adverse event (atrial fibrillation) occurred, indicating that a progressive walking program can be safely recommended for high-risk individuals.

While minor musculoskeletal issues were common, over half of the reported adverse events were unrelated to the exercise program, highlighting the need for strategies to help individuals with chronic illnesses safely resume physical activity after any health setbacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events among high-risk participants in a home-based walking study: a descriptive study. Goodrich, DE., Larkin, AR., Lowery, JC., et al.[2022]

Researchers in resistance training studies often lack clear guidance and motivation for thorough adverse event (AE) reporting, which can lead to inconsistent practices.

There is a need for exercise-specific guidelines for AE reporting, as current standards are perceived as not applicable to exercise trials, highlighting the importance of tailored strategies to improve reporting consistency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Researchers' perspectives on adverse event reporting in resistance training trials: a qualitative study. El-Kotob, R., Pagcanlungan, JR., Craven, BC., et al.[2022]

In a review of over 5,500 participants from 11 physical activity interventions, no serious study-related adverse events were reported, indicating a high level of safety in these exercise programs.

While minor musculoskeletal injuries were noted, the studies emphasized a 'start low and go slow' approach, suggesting that moderate-intensity physical activity is safe and effective for sedentary, chronically ill, or older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening, safety, and adverse events in physical activity interventions: collaborative experiences from the behavior change consortium. Ory, M., Resnick, B., Jordan, PJ., et al.[2022]

Vigorous physical activity can increase the risk of cardiovascular and musculoskeletal complications, especially in sedentary individuals with pre-existing heart conditions, with relative risks of exercise-related cardiac events ranging from 2.1 to 56.

While exercise is generally beneficial for heart health, there is a potential for both underdosing and overdosing, suggesting that there is an optimal level of exercise beyond which the risks may outweigh the benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Putting the benefits and risks of aerobic exercise in perspective. Franklin, BA., Billecke, S.[2022]

Epidemiological studies indicate that regular exercise and physical activity are associated with improved cognitive function and a reduced risk of dementia in humans.

Randomized clinical trials, although limited, suggest that exercise training can positively impact cognitive abilities, supported by animal research showing molecular and cellular benefits from physical activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise, cognition, and the aging brain. Kramer, AF., Erickson, KI., Colcombe, SJ.[2022]

An umbrella review of 20 systematic reviews found that exercise has a small positive effect on cognitive functions in healthy adults aged 55 and older, with a pooled effect size of 0.22, indicating that regular physical activity can enhance cognitive health.

Mind-body exercises, such as yoga or tai chi, showed the greatest benefits, with a moderate effect size of 0.48, suggesting that these types of exercise are particularly effective for improving cognitive function in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mind body exercise improves cognitive function more than aerobic- and resistance exercise in healthy adults aged 55 years and older - an umbrella review. Blomstrand, P., Tesan, D., Nylander, EM., et al.[2023]

Physical activity, particularly aerobic exercise, has been shown to improve cognitive health and protect against age-related brain tissue loss, enhancing cognitive function and task performance across the lifespan.

Exercise influences cognitive function through molecular mechanisms involving energy metabolism and synaptic plasticity, with brain-derived neurotrophic factor playing a key role, suggesting that combining exercise with dietary management can effectively combat neurological and cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of exercise on cognitive abilities. Gomez-Pinilla, F., Hillman, C.[2022]

In a study of 1,131 cognitively healthy older adults at risk for Alzheimer's disease, higher cardiorespiratory fitness (CRF) was linked to better cognitive speed and flexibility.

Insulin resistance was found to mediate the relationship between CRF and cognitive speed, suggesting that improving fitness may enhance cognition by reducing insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin Homeostasis Mediates the Relationship Between Cardiorespiratory Fitness and Cognitive Speed in Aging Adults. McIntyre, CC., Gaitán, JM., Edmunds, KJ., et al.[2023]

In a study of 295 elderly men over 10 years, a decrease in physical activity duration by more than 60 minutes per day was linked to a significant cognitive decline of 1.7 points on the Mini-Mental State Examination, highlighting the importance of maintaining activity levels.

Men who reduced the intensity of their physical activity experienced a cognitive decline that was 3.6 times greater than those who maintained their intensity, suggesting that even moderate physical activity can help protect against cognitive decline in older age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity in relation to cognitive decline in elderly men: the FINE Study. van Gelder, BM., Tijhuis, MA., Kalmijn, S., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Physical activity and exercise training prescriptions for patients. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Heart patient and sports]. [2008]

3. England pubmed.ncbi.nlm.nih.gov

Exercise: friend or foe? [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

[Exercise therapy of atherosclerosis]. [2011]

5. Germany pubmed.ncbi.nlm.nih.gov

[Cardiorespiratory fitness. Importance of sports for health]. [2006]

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

Adverse events in mobility-limited and chronically ill elderly adults participating in an exercise intervention study supported by general practitioner practices. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Adverse events among high-risk participants in a home-based walking study: a descriptive study. [2022]

8. Canada pubmed.ncbi.nlm.nih.gov

Researchers' perspectives on adverse event reporting in resistance training trials: a qualitative study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Screening, safety, and adverse events in physical activity interventions: collaborative experiences from the behavior change consortium. [2022]

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

Putting the benefits and risks of aerobic exercise in perspective. [2022]

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

Exercise, cognition, and the aging brain. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Mind body exercise improves cognitive function more than aerobic- and resistance exercise in healthy adults aged 55 years and older - an umbrella review. [2023]

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

The influence of exercise on cognitive abilities. [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Insulin Homeostasis Mediates the Relationship Between Cardiorespiratory Fitness and Cognitive Speed in Aging Adults. [2023]

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

Physical activity in relation to cognitive decline in elderly men: the FINE Study. [2022]