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)

了解生活方式干预在老年2型糖尿病治疗中的作用是至关重要的 糖尿病和肥胖症。这两种疾病加在一起，几乎是罹患阿尔茨海默病及其相关疾病的风险的两倍 痴呆症。糖尿病中的健康行动(前瞻性)随机对照临床试验记录 10年来为减少卡路里摄入量和增加体力活动而进行的密集生活方式干预 与阿尔茨海默病、相关痴呆症和轻度认知障碍的几率降低30%相关 患有2型糖尿病的超重老年人的损害。然而，建立这一点的力量是有限的 潜在利益坚定[优势比95%CI：0.40-1.22]如果这一发现成立，它提供了一个强有力的信息 支持对这一快速增长的人口进行生活方式干预。令人不安的是，这种干预并不是一致的 对所有成年人都有好处。展望未来还报告说，在837名具有最高水平的 肥胖，例如体重指数40公斤/平方米，密集的生活方式干预似乎增加了患 阿尔茨海默病、相关痴呆症和轻度认知障碍的系数为1.46[0.83-2.56]。大脑 这一队列中的血流数据表明神经血管反应受损是潜在的机制 对这些有害的影响。然而，需要更多的数据来确定这些发现并确定更多 坚定地阐明已观察到的潜在益处和危害的潜在机制。往前看， 只有一项对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 史无前例的、及时的机会来评估一个成功、持续和有据可查的 生活方式干预对认知韧性和阿尔茨海默病、相关痴呆和轻度痴呆的风险有影响 来自美国各地临床中心的大量不同队列中的认知障碍。 糖尿病、阿尔茨海默病和相关痴呆症对健康的作用研究(展望未来) 我们提出的建议将回答这样一个问题，即旨在诱导和维持长期的干预措施 减肥对某些人的认知有益，对另一些人则有害，并决定了基线体重的作用 在修改此关联方面发挥了作用。我们建议重复认知评估和裁决 队列中的认知障碍(N=3,500)，病例数量增加一倍以上：以证实研究结果和 确定有益(炎症、性激素)和有害(血管生成)的潜在机制。组合 近20年来对这些事件和事件的前瞻性队列的丰富描述 认知轨迹(队列中三分之二的人只接受过一次认知评估)，我们将确定因素 与认知韧性有关。我们还将开发公共使用数据库，以促进认知能力的研究 快速增长和研究不足的超重或肥胖老年人群体的健康状况 患有2型糖尿病。我们响应PAR-15-356。

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.