Examining the Effects of Creatine Supplementation and Resistance Training on Cognition and Brain Health in Older Adults With Mild Cognitive Impairment: a 26 Week Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- Corsi Span - Corsi Block Tapping Task
研究概览
简要总结
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.
详细描述
Research objectives:
To evaluate the effects of 26 weeks of creatine supplementation on its own and in combination with progressive resistance training in community-dwelling older adults with mild cognitive impairment on:
- visuospatial working memory (primary objective);
- executive function (working memory, inhibitory control, and mental flexibility), functional mobility, muscle and grip strength, bone density, and blood-based biomarkers for brain health and cognitive decline (secondary objectives); and
- resting state functional activity, hippocampal volume and structural integrity, and key metabolite concentrations in the brain (exploratory objective).
Hypotheses:
It is hypothesized that 26 weeks of creatine supplementation and resistance training in community-dwelling older adults with mild cognitive impairment will: 1) increase visuospatial working memory performance; 2) improve executive function, functional mobility, strength performance, bone density, and blood-based biomarkers for brain health and cognitive decline; and 3) increase resting state functional activity, volume and structural integrity in the hippocampus, and concentrations of key metabolites in the brain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- 未提供
研究组 & 干预措施
Creatine monohydrate supplementation and resistance training
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.
干预措施: Resistance training (Behavioral)
Placebo supplementation and resistance training
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.
干预措施: Resistance training (Behavioral)
Creatine monohydrate supplementation and resistance training
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.
干预措施: Creatine monohydrate (Dietary Supplement)
Creatine monohydrate supplementation and active control group
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.
干预措施: Creatine monohydrate (Dietary Supplement)
Placebo supplementation and active control group
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.
结局指标
主要结局
Corsi Span - Corsi Block Tapping Task
时间窗: Baseline and 26 weeks
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.
Reaction Time - Corsi Block Tapping Task
时间窗: Baseline and 26 weeks
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.
次要结局
- 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)
- Time - Timed Up & Go (TUG) Test(Baseline and 26 weeks)
- Short Physical Performance Battery (SPPB) Score(Baseline and 26 weeks)
- Falls History Questionnaire(Baseline and 26 weeks)
- One Repetition Maximum (1RM) - Muscle Strength(Baseline and 26 weeks)
- Grip Strength(Baseline and 26 weeks)
- Bone Density(Baseline and 26 weeks)
- Cerebral Blood Flow Velocity(Baseline and 26 weeks)
- Biomarker Concentration - Phosphorylated Tau 217 (p tau 217)(Baseline and 26 weeks)
- Biomarker Concentration - Neurofilament Light Chain (NfL)(Baseline and 26 weeks)
- Biomarker Concentration - Glial Fibrillary Acidic Protein (GFAP)(Baseline and 26 weeks)
- Biomarker Concentration - Amyloid Beta 42 (Aβ42)(Baseline and 26 weeks)
- Biomarker Concentration - Creatinine(Baseline and 26 weeks)
- Biomarker Concentration - Brain-Derived Neurotrophic Factor (BDNF)(Baseline and 26 weeks)
- Biomarker Concentration - Insulin-like Growth Factor 1 (IGF-1)(Baseline and 26 weeks)
- Biomarker Concentration - Interleukin 6 (IL-6)(Baseline and 26 weeks)
- Memory Score - Rey Auditory Verbal Learning Test(Baseline and 26 weeks)
- Number of Falls - Falls History and Prospective Reporting(Baseline, 26 weeks, and when they occur)
- Estimated One Repetition Maximum (E1RM) - Muscle Strength(Baseline, midpoint, and 26 weeks)
- Biomarker Concentration - Total Tau (t-tau)(Baseline and 26 weeks)
- 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)
- Time - Timed Up & Go (TUG) Test(Baseline and 26 weeks)
- Short Physical Performance Battery (SPPB) Score(Baseline and 26 weeks)
- Falls History Questionnaire(Baseline and 26 weeks)
- Biomarker Concentration - Insulin-like Growth Factor 1 (IGF-1)(Baseline and 26 weeks)
- Six Minute Walk Test(Baseline and 26 Weeks)
- One Repetition Maximum (1RM) - Muscle Strength(Baseline and 26 weeks)
- Grip Strength(Baseline and 26 weeks)
- Muscle Mass(Baseline and 26 weeks)
- Biomarker Concentration - Glial Fibrillary Acidic Protein (GFAP)(Baseline and 26 weeks)
- Biomarker Concentration - Creatinine(Baseline and 26 weeks)
- Bone Density(Baseline and 26 weeks)
- Cerebral Blood Flow Velocity(Baseline and 26 weeks)
- Biomarker Concentration - Phosphorylated Tau 217 (p tau 217)(Baseline and 26 weeks)
- Biomarker Concentration - Neurofilament Light Chain (NfL)(Baseline and 26 weeks)
- Biomarker Concentration - Amyloid Beta 42 (Aβ42)(Baseline and 26 weeks)
- Biomarker Concentration - Brain-Derived Neurotrophic Factor (BDNF)(Baseline and 26 weeks)
- Biomarker Concentration - Interleukin 6 (IL-6)(Baseline and 26 weeks)
研究者
Lindsay Nagamatsu
Assistant Professor
Western University, Canada