Creatine and Resistance Training for Mild Cognitive Impairment

Overseen By Lindsay Nagamatsu, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Western University, Canada

Must not be taking: NSAIDs

Disqualifiers: Neurological disorders, Kidney disease, Heart disease, Liver abnormalities, Uncontrolled chronic conditions, others

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

Compensation: Varies

Number of Visits: 6

Duration: 26 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this 26-week trial is to learn if creatine supplementation and resistance training (i.e., weightlifting; exercise that increases muscle mass), alone and together, impact cognition, brain health, and physical function in older adults with mild cognitive impairment. Previous studies have shown that resistance training improves cognition and brain health in older adults. Creatine is naturally occurring in the human body and is known to decline with age. Studies have shown that creatine increases muscle mass and bone density in older adults when supplemented. Some research has suggested that creatine may also improve cognition and brain health. However, little is known about how creatine supplementation affects the aging brain and body alone and when combined with resistance training, especially in those with known cognitive impairment. In this study, participants will be randomly assigned to one of four groups: 1) creatine and resistance training, 2) placebo and resistance training, 3) creatine and active control (balance and tone classes), or 4) placebo and active control. Participants in the creatine groups will take creatine every day during the study. Participants in the placebo groups will take a look-alike substance that contains no drug every day during the study. Participants in the resistance training groups will attend three 60-minute classes per week that target each major muscle group and will increase in difficulty during the study. Participants in the active control group will attend three 60-minute classes per week that will consist of balance, stretching, and range of motion exercises. This group accounts for variables such as physical training received by traveling to the training centres, social interaction, and changes in lifestyle secondary to study participation. Researchers will collect information before and after the 26 weeks to see if creatine supplementation and/or resistance training have any effects on cognition, brain health, and/or physical function. The investigators suspect that both creatine supplementation and resistance training will improve cognition, brain health, and physical function alone. However, it is thought that the combination of creatine supplementation and resistance training will improve cognition, brain health, and physical function more.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking medication that may impact kidney function, like ibuprofen or naproxen.

What data supports the effectiveness of the treatment Creatine monohydrate and Resistance training for Mild Cognitive Impairment?

Research suggests that creatine supplementation, especially when combined with resistance training, can improve muscle mass and strength in older adults. Some studies also indicate that creatine may enhance cognitive processing, although findings are mixed and more research is needed specifically in older adults with cognitive decline. ^{1 2 3 4 5}

Is creatine monohydrate safe for humans?

Creatine monohydrate is generally considered safe for healthy adults when taken at a daily dose of 3 grams, although some people may experience minor side effects like stomach upset or muscle cramps. It is not recommended for pregnant or breastfeeding women, and certain forms of creatine may have additional safety concerns. ^{5 6 7 8 9}

How does the treatment of creatine and resistance training for mild cognitive impairment differ from other treatments?

This treatment is unique because it combines creatine, a supplement known for enhancing muscle energy, with resistance training, which has been shown to improve cognitive function and protect brain areas vulnerable to Alzheimer's disease. Unlike standard drug treatments, this approach focuses on physical exercise and dietary supplementation to potentially slow cognitive decline. ^{10 11 12 13 14}

Eligibility Criteria

This trial is for older adults with mild cognitive impairment. Participants should be interested in taking creatine supplements or doing resistance training, like weightlifting. They must not have any health conditions that would make it unsafe to take part in the study.

Inclusion Criteria

Participants must be able to exercise at a moderate pace using resistance training for 60 minutes 3x/week

Participants must be right-handed

Participants must have subjective feelings of memory decline in the past 5 years

Exclusion Criteria

Participants cannot partake or commit to exercise training 3x/week for 26 weeks or have regularly (>1x/week) engaged in exercise training over the past 3 months

Participants cannot partake or commit to consuming a daily supplement for 26 weeks or consumed nutritional supplements containing creatine monohydrate over the past 3 months

I am allergic to creatine monohydrate or dextrose.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants complete baseline assessments including consent, questionnaires, and optional MRI

1 week

1-2 visits (in-person)

Treatment

Participants undergo 26 weeks of creatine supplementation and/or resistance training or active control exercises

26 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Creatine monohydrate
• Resistance training

Trial Overview The study tests if creatine and resistance training can improve brain health, cognition, and physical function over 26 weeks. Participants will be randomly placed into one of four groups: creatine with exercise, placebo with exercise, creatine without exercise, or placebo without exercise.

Participant Groups

Group I: Placebo supplementation and resistance training Experimental Treatment 1 Intervention

Placebo supplementation: Participants in the placebo group will follow the same protocol as the creatine supplementation groups but will consume dextrose powder instead of creatine. Resistance training: All participants will attend three 60-minute exercise classes per week. Classes will consist of a 10-minute warm-up on a treadmill or stationary bike followed up 40 minutes of core-content and ending with a 10-minute cool down and stretch. Resistance training classes will be completed using HUR machines which will target each major muscle group. Progression will follow the 7RM method where load will increase after two sets of 6-8 repetitions can be completed with proper form and range of motion.

Group II: Creatine monohydrate supplementation and resistance training Experimental Treatment 2 Interventions

Creatine supplementation: Participants will consume one serving (0.10g of creatine/kg/day) of creatine monohydrate mixed into at least eight ounces of a beverage of their choice daily. Participants will choose what meal they will take the supplement and will be asked to keep timing consistent throughout the 26 weeks. Resistance training: All participants will attend three 60-minute exercise classes per week. Classes will consist of a 10-minute warm-up on a treadmill or stationary bike followed up 40 minutes of core-content and ending with a 10-minute cool down and stretch. Resistance training classes will be completed using HUR machines which will target each major muscle group. Progression will follow the 7RM method where load will increase after two sets of 6-8 repetitions can be completed with proper form and range of motion.

Group III: Creatine monohydrate supplementation and active control group Experimental Treatment 1 Intervention

Creatine supplementation: Participants will consume one serving (0.10g of creatine/kg/day) of creatine monohydrate mixed into at least eight ounces of a beverage of their choice daily. Participants will choose what meal they will take the supplement and will be asked to keep timing consistent throughout the 26 weeks. Active control group: This group will follow the same protocol as the resistance training group, however, the core-content will consist of balance, stretching, and range of motion exercises. This serves as our active control group to control for socialization and commitment to an exercise program that may influence our outcome measures. This protocol has been used in previous exercise studies and there is no evidence that the balance and tone classes result in cognitive benefits.

Group IV: Placebo supplementation and active control group Active Control 1 Intervention

Placebo supplementation: Participants in the placebo group will follow the same protocol as the creatine supplementation groups but will consume dextrose powder instead of creatine. Active control group: This group will follow the same protocol as the resistance training group, however, the core-content will consist of balance, stretching, and range of motion exercises. This serves as our active control group to control for socialization and commitment to an exercise program that may influence our outcome measures. This protocol has been used in previous exercise studies and there is no evidence that the balance and tone classes result in cognitive benefits.

Who Is Running the Clinical Trial?

Western University, Canada

Lead Sponsor

Trials

270

Recruited

62,500+

Alzheimer Society of Canada

Collaborator

Trials

10

Recruited

2,900+

Findings from Research

Creatine monohydrate is generally considered safe for healthy adults at a daily intake of 3 grams, with some minor side effects like gastrointestinal issues and muscle cramps reported.

While most creatine forms are unlikely to pose safety concerns, there are specific safety concerns associated with creatine orotate, creatine phosphate, and magnesium creatine chelate, indicating that not all creatine supplements are equally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. Andres, S., Ziegenhagen, R., Trefflich, I., et al.[2018]

Creatine monohydrate (CrM) remains the only form of creatine with substantial evidence supporting its bioavailability, efficacy, and safety, as confirmed by a review of various marketed creatine forms.

Despite ongoing claims about other 'novel forms' of creatine, many lack sufficient evidence for effectiveness and safety, and CrM is still the recommended source by professional organizations and regulatory authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review. Kreider, RB., Jäger, R., Purpura, M.[2022]

The BRAIN Training Trial is investigating the effects of high-intensity aerobic interval training (HIIT) and high-intensity power training (POWER) on cognitive function in 160 older adults (≥ 60 years) with mild cognitive impairment (MCI) over 12 months, aiming to provide clearer insights into effective exercise interventions for cognitive health.

The primary outcome will be assessed through a cognitive composite score at baseline, 6 months, and 12 months, which will help determine if these high-intensity exercise programs can significantly improve cognitive performance compared to a sham exercise control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for the BRAIN Training Trial: a randomised controlled trial of Balance, Resistance, And INterval training on cognitive function in older adults with mild cognitive impairment. Valenzuela, T., Coombes, JS., Liu-Ambrose, T., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of Creatine Supplementation on Properties of Muscle, Bone, and Brain Function in Older Adults: A Narrative Review. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis. [2020]

3. Austria pubmed.ncbi.nlm.nih.gov

Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain. [2018]

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

Creatine supplementation combined with resistance training in older men. [2022]

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

Creatine supplementation post-exercise does not enhance training-induced adaptations in middle to older aged males. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review. [2022]

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

Potential benefits of creatine monohydrate supplementation in the elderly. [2019]

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

Comparison of creatine ingestion and resistance training on energy expenditure and limb blood flow. [2013]

10. Germany pubmed.ncbi.nlm.nih.gov

Meta-analysis: Resistance Training Improves Cognition in Mild Cognitive Impairment. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI. [2021]

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

The effects of resistance exercise on cognitive function, amyloidogenesis, and neuroinflammation in Alzheimer's disease. [2023]

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

Longitudinal Cognitive and Physical Training Effectiveness in MCI, Based on the Experience of the Alzheimer's Hellas Day Care Centre. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Study protocol for the BRAIN Training Trial: a randomised controlled trial of Balance, Resistance, And INterval training on cognitive function in older adults with mild cognitive impairment. [2023]