Creatine and Resistance Training in Older Adults With Mild Cognitive Impairment

NCT06948149 | Recruiting

• 1 other identifier: WesternUCanada1
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Creatine; Exercise; Mild Cognitive Impairment (MCI)

Keywords

older adults; physical activity; cognition; neuroimaging; mobility; mild cognitive impairment; creatine; dietary supplementation

Outcome Measures

Primary Outcomes (2)

• Corsi Span - Corsi Block Tapping Task

  Visuospatial working memory will be assessed using the forward and reverse Corsi block-tapping task. Participants will be given an iPad to complete the task. In this task, participants will see nine BLUE blocks on the screen. For each trial, a sequence of blocks will turn RED one by one. Their task is to remember the order in which the blocks light up and then repeat the sequence in the same order (forward Corsi) or backwards (reverse Corsi) by tapping on the blocks. Participants will first complete two practice trials before the true trials to ensure that the instructions are understood. Sequences will become increasingly more difficult with a maximum sequence of nine and a minimum of two. The maximum sequence number that each participant correctly reproduces (Corsi span) will be measured, where higher scores indicate better visuospatial working memory.

  Baseline and 26 weeks

• Reaction Time - Corsi Block Tapping Task

  Visuospatial working memory will be assessed using the forward and reverse Corsi block-tapping task. Participants will be given an iPad to complete the task. In this task, participants will see nine BLUE blocks on the screen. For each trial, a sequence of blocks will turn RED one by one. Their task is to remember the order in which the blocks light up and then repeat the sequence in the same order (forward Corsi) or backwards (reverse Corsi) by tapping on the blocks. Participants will first complete two practice trials before the true trials to ensure that the instructions are understood. Sequences will become increasingly more difficult with a maximum sequence of nine and a minimum of two. Reaction time, or how fast the participant can reproduce each sequence, will be measured.

  Baseline and 26 weeks

Secondary Outcomes (20)

• Interference Score - Stroop Task

  Baseline and 26 weeks

• Span Capacity - Digits Forward and Backward Subtests

  Baseline and 26 weeks

• Time - Trail Making Test (Part B)

  Baseline and 26 weeks

• Memory Score - Rey Auditory Verbal Learning Test

  Baseline and 26 weeks

• Time - Timed Up & Go (TUG) Test

  Baseline and 26 weeks

Other Outcomes (4)

• Hippocampal Volume - Structural MRI

  Baseline and 26 weeks

• Structural Integrity - Structural MRI

  Baseline and 26 weeks

• Resting State Functional Connectivity - Functional MRI

  Baseline and 26 weeks

Study Arms (4)

Creatine monohydrate supplementation and resistance training

EXPERIMENTAL

Creatine supplementation: A relative dosing strategy will be employed (personalized by weight), where 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. Participant's weight will be measured again at midpoint to recalculate supplement dosage accordingly. 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 by 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.

Dietary Supplement: Creatine monohydrate; Behavioral: Resistance training

Creatine monohydrate supplementation and active control group

EXPERIMENTAL

Creatine supplementation: A relative dosing strategy will be employed (personalized by weight), where 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. Participant's weight will be measured again at midpoint to recalculate supplement dosage accordingly. 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.

Dietary Supplement: Creatine monohydrate

Placebo supplementation and resistance training

EXPERIMENTAL

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.

Behavioral: Resistance training

Placebo supplementation and active control group

NO 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.

Interventions

Creatine monohydrate DIETARY_SUPPLEMENT

Participants will consume one serving of creatine daily (0.10g of creatine/kg of body weight). This relative dosing approach ensures that smaller participants do not receive excessive doses, while larger participants receive an adequate amount. There is currently limited evidence to conclude the effectiveness of timing daily creatine intake, but it is recommended that creatine be consumed at mealtime for optimal absorption. Participants will choose what meal they will take the supplement and will be asked to keep timing consistent throughout the study. This daily low dose method was chosen because other methods (high-dose loading) may have negative side effects (e.g., water retention, cramping). The trial duration is also enough time to entire creatine saturation with supplementation.

Creatine monohydrate supplementation and active control group; Creatine monohydrate supplementation and resistance training

Resistance training BEHAVIORAL

Participants will use the programmable weight machines along with free weights to target primary muscle groups. In addition, they will complete mini-squats, mini-lunges, and lunge walks. Participants will complete two sets of 6-8 reps. Training stimulus will be increased using the 7RM method - when 2 sets of 6-8 reps are completed with proper form and without discomfort. The investigators will record the number of sets completed and the load lifted for each exercise for each participant at every class.

Creatine monohydrate supplementation and resistance training; Placebo supplementation and resistance training

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

We will include participants who: 1) are aged \>60; 2) are living independently in the community; 3) have normal or corrected-to-normal vision and hearing; 4) read, write, and speak English fluently; 5) are right-handed (if participating in the MRI component); 6) have subjective feelings of memory decline in the past five years; 7) have telephone Montreal Cognitive Assessment (T-MoCA) scores \<19/22; 8) have high independence, as indicated by Instrumental Activities of Daily Living (IADL) scale \>6/8; 9) have a Geriatric Depression Scale (GDS) score \<6/15; 10) are able to exercise at a moderate pace using resistance training for 60 minutes 3x/week; and 11) receive clearance from a physician to participate in an exercise program at baseline. We will exclude participants who: 1) cannot partake or commit to exercise training 3x/week for 26 weeks or have engaged in resistance training \>1x/week over the past three months; 2) cannot partake or commit to consuming a daily supplement for 26 weeks or have consumed nutritional supplements containing creatine monohydrate over the past three months; 3) have a known allergy to creatine monohydrate or dextrose; 4) have been diagnosed with a neurological disorder (e.g., Alzheimer's disease, Parkinson's disease); 5) have pre-existing kidney disease, heart disease, or liver abnormalities; 6) have one or more uncontrolled chronic or psychiatric conditions (e.g., hypertension, diabetes, depression, anxiety); 7) are taking medication that may impact kidney function (e.g., non-steroidal anti-inflammatory drugs, such as ibuprofen and naproxen); or 8) are ineligible or uncomfortable with blood sampling.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Western University, Canada: lead
• Alzheimer Society of Canada: collaborator

Study Sites (1)

Western University

London, Ontario, N6E 1Z6, Canada

RECRUITING

Related Publications (14)

• Nagamatsu LS, Handy TC, Hsu CL, Voss M, Liu-Ambrose T. Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment. Arch Intern Med. 2012 Apr 23;172(8):666-8. doi: 10.1001/archinternmed.2012.379. No abstract available.

  PMID: 22529236 BACKGROUND

• Stares A, Bains M. The Additive Effects of Creatine Supplementation and Exercise Training in an Aging Population: A Systematic Review of Randomized Controlled Trials. J Geriatr Phys Ther. 2020 Apr/Jun;43(2):99-112. doi: 10.1519/JPT.0000000000000222.

  PMID: 30762623 BACKGROUND

• Smith AN, Sullivan DK, Morris JK, Carbuhn AF, Herda TJ, Taylor MK. Eight weeks of creatine monohydrate supplementation is associated with increased muscle strength and size in Alzheimer's disease: data from a single-arm pilot study. Front Nutr. 2025 Sep 4;12:1670641. doi: 10.3389/fnut.2025.1670641. eCollection 2025.

  PMID: 40977987 BACKGROUND

• Roschel H, Gualano B, Ostojic SM, Rawson ES. Creatine Supplementation and Brain Health. Nutrients. 2021 Feb 10;13(2):586. doi: 10.3390/nu13020586.

  PMID: 33578876 BACKGROUND

• Rawson ES, Venezia AC. Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids. 2011 May;40(5):1349-62. doi: 10.1007/s00726-011-0855-9. Epub 2011 Mar 11.

  PMID: 21394604 BACKGROUND

• Marshall S, Kitzan A, Wright J, Bocicariu L, Nagamatsu LS. Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults. Nutr Rev. 2026 Feb 1;84(2):333-344. doi: 10.1093/nutrit/nuaf135.

  PMID: 40971619 BACKGROUND

• Candow DG, Forbes SC, Chilibeck PD, Cornish SM, Antonio J, Kreider RB. Effectiveness of Creatine Supplementation on Aging Muscle and Bone: Focus on Falls Prevention and Inflammation. J Clin Med. 2019 Apr 11;8(4):488. doi: 10.3390/jcm8040488.

  PMID: 30978926 BACKGROUND

• Vandierendonck A, Kemps E, Fastame MC, Szmalec A. Working memory components of the Corsi blocks task. Br J Psychol. 2004 Feb;95(Pt 1):57-79. doi: 10.1348/000712604322779460.

  PMID: 15005868 BACKGROUND

• Swanson HL. Verbal and visual-spatial working memory: What develops over a life span? Dev Psychol. 2017 May;53(5):971-995. doi: 10.1037/dev0000291.

  PMID: 28459277 BACKGROUND

• McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2007 Sep;14(5):517-28. doi: 10.1080/13825580600788100.

  PMID: 17828627 BACKGROUND

• Alves CR, Santiago BM, Lima FR, Otaduy MC, Calich AL, Tritto AC, de Sa Pinto AL, Roschel H, Leite CC, Benatti FB, Bonfa E, Gualano B. Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken). 2013 Sep;65(9):1449-59. doi: 10.1002/acr.22020.

  PMID: 23554283 BACKGROUND

• Forbes SC, Candow DG, Ferreira LHB, Souza-Junior TP. Effects of Creatine Supplementation on Properties of Muscle, Bone, and Brain Function in Older Adults: A Narrative Review. J Diet Suppl. 2022;19(3):318-335. doi: 10.1080/19390211.2021.1877232. Epub 2021 Jan 27.

  PMID: 33502271 BACKGROUND

• Xu L, Gu H, Cai X, Zhang Y, Hou X, Yu J, Sun T. The Effects of Exercise for Cognitive Function in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Environ Res Public Health. 2023 Jan 7;20(2):1088. doi: 10.3390/ijerph20021088.

  PMID: 36673844 BACKGROUND

• Herold F, Torpel A, Schega L, Muller NG. Functional and/or structural brain changes in response to resistance exercises and resistance training lead to cognitive improvements - a systematic review. Eur Rev Aging Phys Act. 2019 Jul 10;16:10. doi: 10.1186/s11556-019-0217-2. eCollection 2019.

  PMID: 31333805 BACKGROUND

MeSH Terms

Conditions

Motor Activity; Cognitive Dysfunction

Interventions

Creatine; Resistance Training

Condition Hierarchy (Ancestors)

Behavior; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Lindsay Nagamatsu, PhD

CONTACT

519 661-2111; lnagamat@uwo.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants, the study physician, and researchers collecting follow-up data are blinded to dietary supplement group allocation. Creatine and dextrose are both mild, white powders that dissolve into liquid easily. The supplements will be pre-weighted and packaged for each participant by a researcher, and labelled with their participant ID, study name, and date range of supply. In the Letter of Information provided to participants, details regarding the two exercise groups are intentionally not disclosed, such that all participants are only made aware that they will participate in exercise 3x/week. Because all exercise classes take place in the same room to ensure environmental consistency, classes are scheduled at least 30 minutes apart to ensure that participants in different groups do not overlap. Researchers involved in exercise class instruction will not collect endpoint data.
• Purpose: SUPPORTIVE CARE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The investigators will conduct a 26-week double blinded randomized controlled trial using a 2x2 factorial design, with factors of creatine supplementation (vs. placebo) and resistance training (vs. active control). Participants will be randomly assigned to one of the four groups. Sample size calculations in G\*Power assuming a medium effect size (f = 0.25; np2 = 0.06) for the primary outcome measure, alpha=0.05, power=0.80, covariates=1 (baseline Corsi scores) show that we require a total sample size of 128 participants. Conservatively estimating \~10% drop out, a total of 140 participants (35 per group) will be recruited.

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: April 29, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)