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.

了解生活方式干预对于治疗老年 2 型糖尿病患者的作用至关重要 糖尿病和肥胖。这两种疾病加起来几乎使患阿尔茨海默病和相关疾病的风险增加一倍 痴呆症。糖尿病健康行动（Look AHEAD）随机对照临床试验记录 10年的强化生活方式干预以减少热量摄入和增加体力活动 与阿尔茨海默病、相关痴呆症和轻度认知障碍的发病率降低 30% 相关 患有 2 型糖尿病的超重老年人的损害。然而，建立这一点的权力是有限的 潜在益处坚定 [95% CI 比值比：0.40-1.22]。如果这一发现成立，它将向人们提供一个强有力的信息： 支持对这个快速增长的人口进行生活方式干预。令人不安的是，这种干预并不统一 对所有成年人都有好处。 Look AHEAD 还报告称，在 837 名拥有最高水平的个人中， 肥胖，例如体重指数 >40 kg/m2，强化生活方式干预似乎会增加 阿尔茨海默病、相关痴呆症和轻度认知障碍增加 1.46 倍 [0.83-2.56]。大脑的 该队列中的血流数据表明神经血管反应受损是潜在机制 对于这些有害影响。然而，需要更多数据来证实这些发现并确定更多 牢固地揭示了已观察到的潜在利益和危害的潜在机制。展望未来， 唯一一项对 2 型糖尿病患者进行生活方式干预的长期随机试验，提供了 这是一个前所未有的、及时的机会来评估一个成功的、持续的、有据可查的遗产 生活方式干预会影响认知弹性和阿尔茨海默病、相关痴呆症和轻度痴呆症的风险 来自美国各地临床中心的一个庞大且多样化的队列的认知障碍。 糖尿病健康行动阿尔茨海默氏病和相关痴呆症研究（Look AHEAD-MIND） 我们提出的建议将回答这样的问题：干预措施是否旨在诱导和维持长期的 体重减轻对某些人的认知有益，对另一些人的认知有害，并决定了基线体重的作用 发挥修改这种关联的作用。我们建议重复认知评估和裁决 队列中的认知障碍（N = 3,500），病例数量增加了一倍以上：以证实研究结果和 确定潜在的益处（炎症、性激素）和危害（血管生成）机制。组合 Look AHEAD 队列近 20 年来对这些事件案例的丰富描述以及 认知轨迹（队列中三分之二的人仅进行过一次认知评估），我们将确定因素 与认知弹性有关。我们还将开发公共数据库来促进认知研究 快速增长且未被充分研究的超重或肥胖老年人群的健康状况 患有 2 型糖尿病。我们回应 PAR-15-356。