Long-term impact of random assignment to intensive lifestyle intervention on Alzheimers disease and related dementias: The Action for Health in Diabetes ADRD Study (Look AHEAD-MIND)

随机分配强化生活方式干预对阿尔茨海默病和相关痴呆症的长期影响：糖尿病 ADRD 研究中的健康行动（Look AHEAD-MIND）

• 批准号: 9904466
• 负责人: MARK Andrew ESPELAND
• 金额: $ 265.9万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904466
• 关键词: Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Behavior; Behavior Therapy; Blood specimen; Body Weight decreased; Body mass index; Cerebrovascular Circulation; Clinic Visits; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Complex; Data; Databases; Diabetes Mellitus; Disease; Elderly; Energy Intake; Epidemic; Epidemiology; Ethnic Origin; Female; Genotype; Gonadal Steroid Hormones; Health; Health Benefit; Healthcare; Impaired cognition; Impairment; Individual; Inflammation; Intervention; Laboratories; Lead; Life Style; Link; Long-Term Effects; Minority; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Odds Ratio; Older Population; Overweight; Participant; Pathway interactions; Persons; Phenotype; Physical activity; Play; Population; Prevalence; Public Health; Race; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Recommendation; Reporting; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sample Size; Subgroup; Time; Weight; adjudicate; adjudication; angiogenesis; base; brain health; clinical center; cognitive benefits; cognitive function; cognitive testing; cohort; diet and exercise; follow-up; lifestyle intervention; middle age; mild cognitive impairment; modifiable risk; neurovascular; randomized trial; resilience; response; sex; therapy design

It is critical to understand the role of lifestyle intervention for the treatment of older adults with type 2 diabetes mellitus and obesity. Together, these two diseases nearly double one's risk for Alzheimer's disease and related dementias. The Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial documented that 10 years of intensive lifestyle intervention to reduce caloric intake and increase physical activity was associated with a 30% decrease in the odds of Alzheimer's disease, related dementias, and mild cognitive impairment in overweight older adults with type 2 diabetes. However, power was limited to establish this potential benefit firmly [95% CI for odds ratio: 0.40-1.22]. If this finding holds, it provides a powerful message to support lifestyle interventions in this rapidly growing population. Disturbingly, this intervention was not uniformly beneficial for all adults. Look AHEAD also reported that among the 837 individuals with the greatest level of obesity, e.g. body mass index >40 kg/m2, the intensive lifestyle intervention appeared to increase the odds of Alzheimer's disease, related dementias, and mild cognitive impairment by a factor of 1.46 [0.83-2.56]. Cerebral blood flow data in this cohort point towards an impaired neurovascular response as the underlying mechanism for these harmful effects. However, more data are needed to establish these findings and to identify more firmly the mechanisms underlying the potential benefits and harms that have been observed. Look AHEAD, the only long-term randomized trial of lifestyle intervention in persons with type 2 diabetes, provides the unprecedented and timely opportunity to assess the legacy that a successful, sustained, and well-documented lifestyle intervention has on cognitive resilience and the risk of Alzheimer's disease, related dementia, and mild cognitive impairment in a large and diverse cohort drawn from clinical centers across the US. The Action for Health in Diabetes Alzheimer's Disease and Related Dementias Study (Look AHEAD-MIND) that we propose will answer the question of whether interventions designed to induce and sustain long term weight losses lead to cognitive benefit in some, or harm in others, and determine the role that baseline weight plays in modifying this association. We propose to repeat the cognitive assessment and adjudication of cognitive impairment in the cohort (N=3,500), more than doubling the number of cases: to confirm findings and identify potential mechanisms for benefit (inflammation, sex hormones) and harm (angiogenesis). Combining the rich characterization of the Look AHEAD cohort over nearly 20 years with these incident cases and cognitive trajectories (two-thirds of the cohort has had only one cognitive assessment), we will identify factors related to cognitive resilience. We will also develop public-use databases to promote research on cognitive health in the rapidly growing and understudied population of older individuals who are overweight or obese and have type 2 diabetes. We respond to PAR-15-356.

了解生活方式干预在治疗2型糖尿病的老年人中的作用至关重要 Mellitus和肥胖。这两种疾病在一起几乎是一个人患阿尔茨海默氏病的风险及相关的风险 痴呆症。糖尿病中健康动作（前进）随机对照临床试验记录了 减少热量摄入和增加体育锻炼的十年密集的生活方式干预措施是 与阿尔茨海默氏病，相关痴呆和轻度认知的几率下降30％有关 超重老年人患有2型糖尿病的损害。但是，力量仅限于建立这个 潜在的收益牢固[赔率为95％CI：0.40-1.22]。如果这一发现成立，它提供了一个强大的信息 支持这种迅速增长的人口的生活方式干预措施。令人不安的是，这种干预并不统一 对所有成年人有益。展望未来还报告说，在837个人中 肥胖，例如体重指数> 40 kg/m2，密集的生活方式干预似乎增加了几率 阿尔茨海默氏病，相关的痴呆症和轻度认知障碍倍数1.46 [0.83-2.56]。大脑 该队列中的血流数据指向神经血管反应受损的基本机制 这些有害影响。但是，需要更多数据来建立这些发现并确定更多 牢固地观察到了潜在的益处和危害的基础机制。向前看， 只有对2型糖尿病患者的生活方式干预的长期随机试验才能提供 空前且及时的机会来评估成功，持续和据可记录的遗产 生活方式干预对认知韧性和阿尔茨海默氏病，相关痴呆和温和的风险 来自美国临床中心的大型和多样化的队列中的认知障碍。 阿尔茨海默氏病和相关痴呆症研究中健康状况的作用（提前查看） 我们建议将回答旨在诱导和维持长期干预措施的问题 体重减轻会导致某些人的认知益处，或者在其他方面受到伤害，并确定基线重量的作用 扮演修改该关联。我们建议重复认知评估和裁决 队列中的认知障碍（n = 3,500），案例数量增加了一倍以上：确认发现和 确定益处（炎症，性激素）和危害（血管生成）的潜在机制。结合 这些事件案件和 认知轨迹（三分之二的队列只有一个认知评估），我们将确定因素 与认知弹性有关。我们还将开发公共用途数据库以促进认知研究 超重或肥胖的老年人的迅速成长且研究不足的人口 患有2型糖尿病。我们回应15-356杆。