Napping, Sleep, Cognitive Decline and Risk of Alzheimer's Disease

项目总结 午睡在老年人中非常普遍，特别是在阿尔茨海默病患者中，但纵向的 人们对午睡对神经退化的影响知之甚少。虽然越来越多的证据表明睡眠 干扰会增加患阿尔茨海默病的风险，目前尚不清楚午睡是否作为 24小时的睡眠-醒来周期，可能与夜间睡眠一样是阿尔茨海默氏病的重要风险因素。这 岳冷博士申请独立之路奖(K99/R00)打算通过以下方式填补这一知识空白 基于她之前的流行病学研究，该研究表明自我报告的午睡与风险之间存在关联 ，并将为冷博士提供进一步的有针对性的培训，以 促进她转变为午睡、睡眠和认知老化领域的独立研究人员。这个 K99阶段的研究目标是确定动作图的独立和纵向影响- 午睡对认知功能下降和轻度认知障碍(MCI)和阿尔茨海默氏症发病风险的影响 并探索和阐明可能的机制，包括炎症、氧化应激、 代谢失调和其他合并症。午睡的不同维度(即，意图、持续时间、 频率和定时)也将被探索并用于通知R的治疗计划的发展 相位。该项目将利用NIA资助的两项最先进的老龄化前瞻性研究的数据， 男性骨质疏松性骨折研究(MROS)和骨质疏松性骨折研究(SOF)，均为24小时 午睡和夜间睡眠的动态记录，广泛使用的认知测试和血清生化 措施。这些研究活动将辅以1)病因学、诊断和培训方面的重点培训 阿尔茨海默氏症和其他痴呆症的管理；2)干预性研究的设计和实施；3)衰老- 相关的安眠药。培训目标将由一个多学科指导团队监督，该团队由Dr。 克里斯汀·亚菲，医学博士，精神病学、神经学和流行病学教授。培训阶段结束时，Dr。 Leng将发展睡眠测量和干预方面的专业知识，以成功过渡到R00 项目，该项目旨在开发和试点测试一种结合了强光疗法和 改良认知行为疗法治疗失眠改善失眠患者24小时睡眠模式 MCI或轻度阿尔茨海默病，最终目的是降低阿尔茨海默病的发病或进展风险。 合并后的5年研究和培训计划将使冷博士能够建立一个独立的研究 致力于改善睡眠和衰老结果的计划。目前的提案还将 具体地说，1)提前了解午睡的影响，这是一种非常常见但研究不足的 老年人的行为，关于认知老化；2)开发一种新的睡眠治疗计划，针对患有 MCI；以及3)对24小时睡眠模式的干预进行一系列研究，以改善认知 结果和预防阿尔茨海默病的高危人群。

PROJECT SUMMARY Napping is highly prevalent in the elderly, particularly in patients with Alzheimer's disease, but the longitudinal effects of napping on neurodegeneration are poorly understood. While growing evidence suggests that sleep disturbances lead to increased risk of Alzheimer's disease, it is unclear whether napping, as a crucial part of the 24-h sleep-wake cycle, could be as important a risk factor as nocturnal sleep for Alzheimer's disease. This Pathway to Independence Award (K99/R00) application by Dr. Yue Leng intends to fill this knowledge gap by building on her prior epidemiologic research that suggests associations between self-reported napping and risk of various adverse health outcomes in the elderly, and will provide Dr. Leng with further focused trainings to facilitate her transition into an independent researcher in the field of napping, sleep and cognitive aging. The research aims during the K99 phase are to determine the independent and longitudinal effects of actigraphy- measured napping on cognitive decline and risk of incident mild cognitive impairment (MCI) and Alzheimer's disease, and to explore and elucidate potential mechanisms, including inflammation, oxidative stress, metabolic dysregulation and other comorbidities. Different dimensions of napping (i.e., intention, duration, frequency and timing) will also be explored and used to inform the development of a treatment program in R phase. This project will leverage data from two NIA-funded state-of-the-art prospective studies of aging, the Osteoporotic Fractures in Men (MrOS) Study and Study of Osteoporotic Fractures (SOF), both with 24-hour actigraphy recordings of napping and nocturnal sleep, widely used cognitive tests and serum biochemical measures. These research activities will be complemented by focused trainings in 1) etiology, diagnosis and management of Alzheimer's and other dementias; 2) interventional study design and conduct; and 3) aging- related sleep medicine. The training goals will be supervised by a multidisciplinary mentorship team, led by Dr. Kristine Yaffe, MD, Professor of Psychiatry, Neurology and Epidemiology. By the end of the training phase, Dr. Leng will develop expertise in sleep measurement and intervention to successfully transition into the R00 project, which aims to develop and pilot test a treatment program that incorporates bright light therapy and a modified cognitive behavioral therapy for insomnia (CBT-i) to improve 24-hour patterns of sleep in patients with MCI or mild Alzheimer's disease, with the ultimate aim of decreasing risk of Alzheimer's onset or progression. The combined 5-year research and training plan will allow Dr. Leng to establish an independent research program dedicated to the improvement of both sleep and aging outcomes. The current proposal will also specifically 1) advance knowledge about the effects of napping, an extremely common but understudied behavior in the elderly, on cognitive aging; 2) develop a novel sleep treatment program targeting patients with MCI; and 3) pilot a line of research on interventions of 24-h sleep patterns in order to improve cognitive outcomes and prevent Alzheimer's disease in high-risk population.