Lifestyle Interventions for Mild Cognitive Impairment

Overseen By Nicole D Anderson, PhD

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: University of Waterloo

Disqualifiers: Dementia, Stroke, Major psychiatric disorder, others

Compensation: Varies

Number of Visits: 4

Duration: 6 months

140 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study is to investigate the feasibility of a virtually-delivered 6-month exercise and nutrition intervention in older adults with executive subjective cognitive decline (SCD). Feasibility will be determined by recruitment, retention, and adherence rates. Preliminary changes in cognition, physical function, and quality of life will be assessed as secondary outcomes. The study will recruit 140 participants aged 65 to 80 who report they feel that their memory or other thinking abilities are declining. Participants will be randomized into one of four study arms receiving different combinations of healthy lifestyle interventions. Assessments will be conducted virtually at baseline, post-intervention (6 months), and follow-up (12 months). All intervention sessions and assessment visits will be conducted online using the Zoom Healthcare platform and participants will log on using their own devices from home.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment LEAD 2.0 for mild cognitive impairment?

Research shows that combining physical exercise and diet can help improve cognitive function in people with mild cognitive impairment, potentially slowing the progression to dementia. Additionally, mind-body exercises and lifestyle changes have been found to enhance cognitive performance in middle-aged and older adults with mild cognitive impairment. ^{1 2 3 4 5}

Is the LEAD 2.0 intervention generally safe for humans?

Lifestyle clinical trials, including those involving exercise and diet, are generally safe with no significant increase in serious adverse events compared to control groups. However, some trials involving diet/supplement and multi-modal interventions showed an increased risk of adverse events, so these results should be considered carefully. ^{1 6 7 8 9}

How is the LEAD 2.0 treatment different from other treatments for mild cognitive impairment?

The LEAD 2.0 treatment is unique because it focuses on lifestyle changes, combining exercise and diet, rather than relying on medication. This approach is designed to improve cognitive function and brain health through non-pharmacological means, which may be more accessible and sustainable for some patients. ^{1 7 10 11 12}

Research Team

Laura Middleton, PhD

Principal Investigator

University of Waterloo

Eligibility Criteria

The LEAD 2.0 trial is for adults aged 65-80 in Quebec, Ontario, Manitoba, and Saskatchewan who feel their cognitive abilities are declining but do not have dementia or other severe brain conditions. They should be physically inactive (<75min/week of exercise), have a poor diet, and be able to use a computer with internet for remote participation.

Inclusion Criteria

I am between 65 and 80 years old.

Reside in Quebec, Ontario, Manitoba, or Saskatchewan

Low physical activity levels (<75 minutes/week of moderate/vigorous physical activity)

Exclusion Criteria

I have been diagnosed with a chronic brain condition.

Sensory impairments that hinder participation in the intervention or assessments

Major psychiatric disorder

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (virtual)

Treatment

Participants engage in a 6-month virtual exercise and nutrition intervention

6 months

Weekly virtual sessions

Follow-up

Participants are monitored for changes in cognition, physical function, and quality of life

6 months

2 visits (virtual)

Treatment Details

Interventions

• LEAD 2.0

Trial Overview This study tests if older adults can stick to a 6-month virtual program focused on exercise and nutrition to improve cognition, physical function, and quality of life. Participants will join one of four groups receiving different combinations of exercises (EX), stretching (STRETCH), dietary changes (DIET), or educational sessions (ED).

Participant Groups

Group I: EX + DIET Experimental Treatment 2 Interventions

Participants will engage in 3 sessions per week (2 EX, 1 DIET, totaling 4 hours per week), consisting of two virtual group sessions (totaling 3 hours) and one independent session (1 hour) (Table 1). Virtual group sessions will occur in groups of 6-8 participants using the Zoom Healthcare platform (on a computer or tablet).

Group II: EX + ED Active Control 2 Interventions

Participants will engage in 3 sessions per week (2 EX, 1 ED, totaling 4 hours per week), consisting of two virtual group sessions (totaling 3 hours) and one independent session (1 hour) (Table 1). Virtual group sessions will occur in groups of 6-8 participants using the Zoom Healthcare platform (on a computer or tablet).

Group III: STRETCH + DIET Active Control 2 Interventions

Participants will engage in 3 sessions per week (2 STRETCH, 1 DIET, totaling 4 hours per week), consisting of two virtual group sessions (totaling 3 hours) and one independent session (1 hour) (Table 1). Virtual group sessions will occur in groups of 6-8 participants using the Zoom Healthcare platform (on a computer or tablet).

Group IV: STRETCH + ED Placebo Group 2 Interventions

Participants will engage in 3 sessions per week (2 STRETCH, 1 ED) totaling 4 hours per week), consisting of two virtual group sessions (totaling 3 hours) and one independent session (1 hour) (Table 1). Virtual group sessions will occur in groups of 6-8 participants using the Zoom Healthcare platform (on a computer or tablet)

Who Is Running the Clinical Trial?

University of Waterloo

Lead Sponsor

Trials

132

Recruited

221,000+

Baycrest

Collaborator

Trials

46

Recruited

6,900+

University of Ottawa

Collaborator

Trials

231

Recruited

267,000+

Université de Montréal

Collaborator

Trials

223

Recruited

104,000+

Findings from Research

Recruitment for a one-year exercise trial in individuals with mild cognitive impairment (MCI) was significantly more successful at a non-medical sport university compared to traditional memory clinics, highlighting the importance of the environment in attracting participants.

The study suggests that non-medical settings and community-based physical activity programs may enhance recruitment and retention in prevention trials for MCI, which is crucial for the success of such interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Recruiting of Older Subjects with Mild Cognitive Impairment for Exercise Trials: Community Readiness is Pivotal. Sanders, ML., Stuckenschneider, T., Devenney, KE., et al.[2022]

Scheduled moderate to high-intensity physical exercise, performed 3 to 5 days a week, combined with dietary patterns like the Mediterranean or DASH diet, significantly improves cognitive function in individuals over 45 with mild cognitive impairment (MCI).

Combining physical exercise with cognitive stimulation exercises enhances the benefits, leading to better functionality and quality of life for those with MCI, although the variability in study designs complicates specific recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of physical exercise and diet based interventions on the evolution of cognitive impairment to dementia in subjects older than 45 years. A systematic review.] Ballarín-Naya, L., Malo, S., Moreno-Franco, B.[2023]

A systematic review of 27 studies involving 2565 participants with mild cognitive impairment (MCI) found that physical and mental exercises, such as Tai Chi and dance, significantly improved cognitive performance, as indicated by various cognitive assessment scores.

These exercises not only enhanced cognitive abilities but also positively affected biomarkers, increasing levels of the beneficial αβ1-42 protein and decreasing Tau protein levels, suggesting a potential mechanism for their efficacy in managing MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of mind-body exercise on cognitive performance in middle-aged and older adults with mild cognitive impairment: A meta-analysis study. Cai, H., Zhang, K., Wang, M., et al.[2023]

The pilot study involving 19 older adults with mild cognitive impairment (MCI) showed that combining cognitive training, mind-body exercise, and nurse-led risk factor modification (CPR) was feasible and had preliminary benefits, particularly in reducing cognitive decline and improving quality of life.

The nurse-led risk factor modification (RFM) group demonstrated significant improvements in cognitive scores, while the CPR group showed reductions in health service costs, indicating that both interventions could be effective strategies for managing MCI in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot feasibility randomized controlled trial on combining mind-body physical exercise, cognitive training, and nurse-led risk factor modification to reduce cognitive decline among older adults with mild cognitive impairment in primary care. Xu, Z., Zhang, D., Lee, ATC., et al.[2022]

An 8-week randomized controlled trial with 119 participants showed that a multidomain intervention significantly reduced lifestyle risk factors for Alzheimer's disease and improved cognitive scores compared to a control group.

The improvements in lifestyle were primarily due to increases in protective factors rather than a decrease in risk factors, indicating that positive lifestyle changes can enhance cognitive function in individuals with subjective cognitive decline or mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifestyle Risk Factors and Cognitive Outcomes from the Multidomain Dementia Risk Reduction Randomized Controlled Trial, Body Brain Life for Cognitive Decline (BBL-CD). McMaster, M., Kim, S., Clare, L., et al.[2021]

A retrospective analysis of lifestyle clinical trials for cognitive health in older adults found that overall, these trials are safe, with no significant increase in serious adverse events (SAEs) compared to control groups.

However, specific intervention types, particularly Diet/Supplement and Multi-modal trials, showed increased risks for SAEs and mortality, highlighting the need for careful consideration and improved reporting of trial results to ensure safety and transparency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Analysis of Serious Adverse Events and Deaths in US-Based Lifestyle Clinical Trials for Cognitive Health. Key, MN., Shaw, AR., Erickson, KI., et al.[2023]

In a study of 113 older adults with Mild Cognitive Impairment (MCI), a 7-month combined physical-cognitive training program significantly improved cognitive status compared to those who did not receive training.

The training also increased cerebral blood flow in the parahippocampal area, suggesting a positive impact on brain health, while no significant effect on gray matter volume loss was observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study. [2018]

This study will assess the feasibility and acceptability of a 24-week intervention combining the Mediterranean diet and physical activity in 108 participants aged 55 to 74 years at risk of dementia, aiming to evaluate its effectiveness in reducing dementia risk.

The trial will monitor various outcomes, including cognitive function and brain health, to inform the design of a larger efficacy trial, highlighting the potential of lifestyle changes in dementia prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and acceptability of a multi-domain intervention to increase Mediterranean diet adherence and physical activity in older UK adults at risk of dementia: protocol for the MedEx-UK randomised controlled trial. Shannon, OM., Lee, V., Bundy, R., et al.[2022]

A systematic review of 41 studies involving 3119 participants with mild cognitive impairment (MCI) and dementia found that the average adherence rate to exercise interventions was 70%, indicating a generally positive response to physical activity in this population.

Adherence to exercise was notably higher in interventions focused on endurance and resistance training rather than walking, suggesting that these types of exercises may be more effective in promoting consistent participation among individuals with MCI and dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to exercise interventions in older people with mild cognitive impairment and dementia: A systematic review and meta-analysis. Di Lorito, C., Bosco, A., Booth, V., et al.[2021]

In a study of 855 older adults with mild cognitive impairment, longer total sleep time was found to be inversely associated with brain glucose metabolism, suggesting that more sleep may support better brain function.

The research indicates that sleep duration could be a modifiable risk factor for dementia, particularly in individuals already experiencing mild cognitive impairment, highlighting the importance of sleep in cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Modifiable Lifestyle Factors With Cortical Amyloid Burden and Cerebral Glucose Metabolism in Older Adults With Mild Cognitive Impairment. Kimura, N., Aso, Y., Yabuuchi, K., et al.[2020]

A systematic review of 10 randomized controlled trials involving 635 patients with mild cognitive impairment (MCI) found that physical exercise significantly improved cognitive function, as measured by the MMSE scores, and physical performance, as indicated by TUG scores.

The results suggest that regular exercise training can be beneficial for individuals with MCI, highlighting the need for ongoing exercise interventions and more high-quality research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training for cognitive and physical function in patients with mild cognitive impairment: A PRISMA-compliant systematic review and meta-analysis. Zhou, Y., Li, LD.[2022]

A 12-month structured exercise program did not lead to significant improvements in cognitive performance for individuals with mild cognitive impairment (MCI) compared to a non-exercise control group, based on a study of 183 participants.

However, the exercise intervention did result in improved physical fitness, as indicated by higher VO2 peak levels in the exercise groups, suggesting that while cognitive benefits were not observed, enhanced physical fitness may play a role in long-term disease progression and should be explored further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NeuroExercise: The Effect of a 12-Month Exercise Intervention on Cognition in Mild Cognitive Impairment-A Multicenter Randomized Controlled Trial. Stuckenschneider, T., Sanders, ML., Devenney, KE., et al.[2021]

References

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

Real World Recruiting of Older Subjects with Mild Cognitive Impairment for Exercise Trials: Community Readiness is Pivotal. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

[Effect of physical exercise and diet based interventions on the evolution of cognitive impairment to dementia in subjects older than 45 years. A systematic review.] [2023]

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

Effects of mind-body exercise on cognitive performance in middle-aged and older adults with mild cognitive impairment: A meta-analysis study. [2023]

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

A pilot feasibility randomized controlled trial on combining mind-body physical exercise, cognitive training, and nurse-led risk factor modification to reduce cognitive decline among older adults with mild cognitive impairment in primary care. [2022]

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

Lifestyle Risk Factors and Cognitive Outcomes from the Multidomain Dementia Risk Reduction Randomized Controlled Trial, Body Brain Life for Cognitive Decline (BBL-CD). [2021]

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

A Retrospective Analysis of Serious Adverse Events and Deaths in US-Based Lifestyle Clinical Trials for Cognitive Health. [2023]

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

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Feasibility and acceptability of a multi-domain intervention to increase Mediterranean diet adherence and physical activity in older UK adults at risk of dementia: protocol for the MedEx-UK randomised controlled trial. [2022]

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

Adherence to exercise interventions in older people with mild cognitive impairment and dementia: A systematic review and meta-analysis. [2021]

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

Association of Modifiable Lifestyle Factors With Cortical Amyloid Burden and Cerebral Glucose Metabolism in Older Adults With Mild Cognitive Impairment. [2020]

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

Exercise training for cognitive and physical function in patients with mild cognitive impairment: A PRISMA-compliant systematic review and meta-analysis. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

NeuroExercise: The Effect of a 12-Month Exercise Intervention on Cognition in Mild Cognitive Impairment-A Multicenter Randomized Controlled Trial. [2021]