Effect of a Multidomain Intervention Plus Turmeric on the Prevention of Cognitive Decline in People Over 55 Years of Age With Insulin Resistance: A Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Improving insulin resistance by 5%.
研究概览
简要总结
Introduction: The Insulin resistance itself has been recognized as an independent risk factor for dementia development. Insulin plays an important role in the regulation of muscle function and the processes of learning and memory. Insulin resistance is associated with increased inflammation and oxidative stress. These processes are involved in the pathophysiology of neurodegenerative diseases. Thus, reducing IR could have implications for improving metabolism, muscle, and cognitive function.
Methods and analysis. The investigators will conduct a randomized, double-blind, placebo-controlled clinical trial in which a multidomain program, including an aerobic and cognitive exercise program, will be evaluated. The latter is an exercise program conducted on a checkered mat and will be randomized to participants receiving turmeric plus black pepper or placebo. Participants are affiliated with the Mexican Social Security Institute (IMSS) and are between 55 and 74 years old. The program will last for 24 weeks; after 52 weeks, it will be repeated. The outcomes that the investigators will evaluate are: global cognitive function, specific cognitive function, and the investigators will evaluate serum markers of inflammation, oxidative stress, and GSK-3beta levels. The effect of the interventions on each variable will be analyzed by ANOVA, and a multivariate analysis study with multiple linear regression will be conducted.
Ethics and dissemination of the study: the study was approved by the IMSS National Ethics and Research Committee all participants provided written informed consent prior to their participation.
详细描述
Dementia is characterized by cognitive impairment, which affects independence in activities of daily living (1). Worldwide, approximately 47 million people were living with dementia in 2015, and before the COVID-19 pandemic, the number of cases was expected to triple by 2050 (2). The prevalence of dementia in Latin America and the Caribbean is 10.66%, and dementia is more prevalent in women than men (7.26%).
Observational studies have shown that dementia and cognitive decline can be prevented by reducing vascular risks and improving healthier lifestyles (6). The key is to modify lifestyle habits before the development of disease symptoms. To achieve this, it is important to characterize populations with intact cognitive function or with some concern without symptoms of cognitive decline (6).
Interventions to treat dementia have been nonpharmacological, including nutrition, cognitive stimulation, physical exercise, and multi-domain (combination of more than two components or domains). However, the best results for dementia prevention have been for multi-domain interventions in individuals with intact cognitive function or those with some concerns (10). The domains included in all multi-domain interventions were physical activity, nutrition, and cognitive training. The Mind and Movement for Cognitive Health Program (MeMo Health-Cog) is a program that includes three basic components: a) a moderate physical activity routine through a one-hour/day routine of combined aerobic exercises, b) cognitive training with the checkered mat and c) a motivational educational program that consists of weekly talks on topics of healthy active aging, sports for older adults, basic nutrition recommendations, health topics, and socialization; these talks last between 10 and 15 minutes. Physical and cognitive activities are a one-hour routine each day, and they can be performed three days a week. The duration of the entire program is 24 weeks. It is important to mention that the educational program encourages light physical activities with the 24-hour healthy educational program, which are recommendations of Canadian origin that allow improving behaviors related to movement, that is, moderate and light physical activities, adequate sleep duration, and limitations of sitting (13).
An important and emerging concept is insulin resistance at the brain level, where insulin signaling plays crucial roles in physiology and therefore affects cognitive function. Altered insulin signaling in brain tissue contributes to Alzheimer's disease (AD) through increased beta-amyloid and tau neurofibrillary tangle formation and other brain damage mechanisms. Insulin resistance not only affects systemic metabolism and directly influences the brain by altering insulin-related brain pathways (20).
b. Mechanisms of insulin resistance, inflammation, and oxidative stress The molecular mechanisms of type 2 diabetes (T2DM) are characterized by an alteration in the regulation of carbohydrate, lipid, and protein metabolism, as a consequence of a decrease in insulin secretion and resistance to its effect (21).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The researchers will use key-labeled bottles to designate placebo vs turmeric; the participants, doctors, and staff do not know which group each bottle corresponds to. Only two people from the research team know which group each bottle corresponds to.
入排标准
- 年龄范围
- 55 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Minimum Age: 55 Years Maximum Age: 70 Years Sex: All Gender Based: No Accepts Healthy Volunteers: No Criteria: Inclusion criteria.
- •1. With 55-70 years of age.
- •2. They have self-reported cognitive concerns (ie, have answered "yes" to the question: "Do you feel like your memory or thinking skills have gotten worse recently?").
- •3. The participant has insulin resistance measured with HOMA IR index > 2.
- •4. They demonstrate functional independence in activities of daily living and instrumental activities of daily living.
- •5. They have symptoms or signs of underlying cognitive dysfunction without a diagnosis of dementia (ie, confirmed by a review of their health records and a Mini Mental State Exam [MMSE] score> 24).
- •6. If the participant are a woman, one year after having gone through menopause.
排除标准
- •1. With depression (score> 15 according to the Center for Epidemiological Studies Depression Scale - Revised [CESD-R]).
- •2. With clinically significant neurological or psychiatric disorders (eg, Parkinson's, schizophrenia).
- •3. With a recent severe cardiovascular event (eg, myocardial infarction, stroke).
- •4. With a major orthopedic condition (eg, severe osteoarthritis).
- •5. With blood pressure that is unsafe for exercise (ie,> 180/100 mmHg or <100/60 mmHg).
- •6. With a severe visual or auditory impairment.
- •7. With an unwillingness to adhere to the intervention schedules.
- •8. Patients with active cancer, who are undergoing chemotherapy, radiotherapy, or other treatments aimed at eradicating cancer and who have been undergoing treatment during the last year.
- •9. Elimination: participants with incomplete data and who have not complied with the intervention by 80%.
研究组 & 干预措施
Placebo
500mg capsule grenadine every 12 hours. Measurement of insulin resistance, global cognitive function (subjective and objective), specific cognitive function (executive function/mental flexibility, verbal learning and memory, and verbal fluency), motor function (gait speed, grip strength, balance, and rising from a chair); reduction of biomarkers of inflammation (IL-6, TNF-α, IL-10), endothelial dysfunction (ICAM-1, E-selectin, VCAM-1), and oxidative stress (MDA, GSH) in people aged 55-70 years with insulin resistance; as well as the post-intervention effect at 28 weeks.
干预措施: Control: Placebo. 500mg gelatin in capsules 2 times a day (Other)
Turmeric extract intervention
Multidomain program (MeMo-Health-Cog-4) with 500 mg/day of turmeric plus 5 mg of black pepper for 24 weeks against a multidomain program (MeMo-Health-Cog-4) with a placebo for the improvement of insulin resistance, global cognitive function (subjective and objective), specific cognitive function (executive function/mental flexibility, verbal learning and memory, and verbal fluency), motor function (gait speed, grip strength, balance, and rising from a chair); reduction of biomarkers of inflammation (IL-6, TNF-α, IL-10), endothelial dysfunction (ICAM-1, E-selectin, VCAM-1), and oxidative stress (MDA, GSH) in people aged 55-70 years with insulin resistance; as well as the post-intervention effect at 28 weeks.
干预措施: Turmeric extract (Dietary Supplement)
结局指标
主要结局
Improving insulin resistance by 5%.
时间窗: 12, 24 y 52 weeks
The investigadors will measure various parameters of insulin resistance such as glycated hemoglobin, insulin resistance index, and we will measure the improvement of these parameters.
General Cognitive funtion
时间窗: Time Frame: 0, 24 and 52 weeks
General cognitive function assessed by the Montreal Cognitive Assessment (MoCA) test on a scale of 0-30 points. Scores are interpreted as follows: \>26 indicates no dementia, 18-26 mild cognitive impairment, 6-10 moderate dementia.
Specific domains of cognitive function
时间窗: 0, 24, 52 weeks
Measured through composite scores: Executive function/mental flexibility will be measured with the Trail Making Tests, Part A and Part B. The results for both TMT-A and TMT-B are reported as the number of seconds required to complete a task. Processing speed (using the Digit Symbol Substitution Test) will be measured as the total correct number-symbol matches achieved in 90 seconds. Verbal learning and memory will be assessed through Rey's Auditory Verbal Learning Test (RAVLT), that consists of documenting the number of words remembered from a list of 15 words presented in two separate moments; this test allows evaluation of the RAVLT-Immediate and RAVLT-Percent Forgetting. Verbal fluency (semantic, animal naming, and phonemic) will be measured by using the Controlled Oral Word Association Test and assessed through the total number of words identified by category and letter.
Oxidative stress.
时间窗: 0, 12. 24. 52 weeks.
The investigators will measure several parameters of oxidative stress, including 4-hydroxynonenal (4OH-N), malonaldehyde (MDA), quinones, and glutathione system activity.
次要结局
- Usual walking and dual-task gait(0 and 52 weeks)
- Quality of life as measured by SF-12(0 and 52 weeks)
- Cardiovascular biomarkers and endothelial function: MCP-1, ICAM VCAM and Selectin(0 and 52weeks)
研究者
Carlos Arturo Hernández Esquivel
Research
Instituto Mexicano del Seguro Social