Sleep and circadian dysfunction in ageing and neurodegeneration: a life course and biomarker study of the British 1946 birth cohort.

衰老和神经退行性疾病中的睡眠和昼夜节律功能障碍：对英国 1946 年出生队列的生命历程和生物标志物研究。

• 批准号: MR/Y009452/1
• 负责人: Josh King-Robson
• 金额: $ 27.9万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY009452%2F1
• 关键词: Sleep; circadian; dysfunction; ageing; neurodegeneration

Sleep is an essential requirement of all animal life, including humans, who spend around a third of their life asleep. It is controlled by an internal biological clock, our circadian rhythm, which controls the timing of when we rest, sleep, and are active. We do not understand why humans need to sleep, however, it is becoming clear that sleep and circadian rhythms are linked to cognition (brain functions such as thinking and memory). Sleep and circadian rhythms are disrupted in neurological diseases where the brain is gradually damaged over time, called neurodegenerative diseases. These diseases include Alzheimer's disease, the most common cause of dementia worldwide and a leading cause of death. Alzheimer's disease causes alterations in sleep and circadian rhythms. These changes can occur before other symptoms and may help us identify those who will develop these diseases. Early diagnosis is essential as it enables treatment before damage to the brain is too widespread. Evidence is also emerging that abnormal sleep and circadian rhythms may be part of the cause of Alzheimer's disease.We do not know why abnormal sleep and circadian rhythms emerge, how they change over time, or how they relate to cognition in the long term. It is unclear if disturbed circadian rhythms are early signs of disease, or if they precede and cause neurodegenerative diseases. To answer these questions we must analyse sleep and circadian rhythms in detail. Bed mats placed under the mattress, and worn devices, called actigraphy, allow us to closely monitor sleep and circadian rhythms in patients' own homes. The genes and sleep-promoting chemicals which control sleep and circadian rhythms can be detected in the blood and spinal fluid. Advanced brain imaging, blood and spinal fluid analysis allows us to detect signs of damage and neurodegenerative diseases in the brain.The Medical Research Council National Survey for Health and Development (NSHD) offers a unique opportunity to examine the effects of abnormal sleep and circadian rhythms on cognition and neurodegenerative disease. It has followed 5362 people born in Britain on the same week in 1946, with regular questionnaires throughout their lives. The Insight 46 study has recruited is recruiting a further 872 people from NSHD to have advanced brain imaging, detailed cognitive assessments, actigraphy, genetic testing, and sampling of their blood and spinal fluid to analyse for evidence of neurodegeneration. 250 people will undergo repeat assessments, and 100 will have at least 6 months of bed mat analysis. These repeated and prolonged assessment allow particularly detailed examination of changes in sleep and circadian rhythms over time, and how they relate to progressive changes in cognition, brain imaging, and in the blood or spinal fluid. We will also examine the chemicals that control sleep and circadian rhythms in the spinal fluid of 375 participants, and examine how the genes that control sleep or make you more likely to develop Alzheimer's disease relate to sleep, circadian rhythms, and signs of neurodegenerative disease in old age. One fifth of those within Insight 46 already have early signs of Alzheimer's disease.For my PhD I plan to examine how sleep and circadian rhythms relate to cognition and neurodegenerative disease. Using sleep and circadian rhythm questionnaire data from birth to the seventh decade with sleep data from actigraphy and bed mats, I will examine sleep and circadian rhythms over the human lifetime in unparalleled detail. Combining this with the advanced brain imaging, cognitive, blood and spinal fluid data already collected from Insight 46 will allow me to explore how sleep and circadian rhythms relate to cognition and neurodegenerative disease. Finally, I will examine how this process is controlled by our genes, and sleep promoting chemicals, and whether failures in this control system are related to cognition and neurodegenerative disease.

睡眠是包括人类在内的所有动物生命的基本需求，人类一生中大约三分之一的时间都在睡眠中度过。它由内部生物钟（我们的昼夜节律）控制，它控制着我们休息、睡眠和活动的时间。我们不明白为什么人类需要睡眠，但是，越来越清楚的是，睡眠和昼夜节律与认知（思维和记忆等大脑功能）有关。睡眠和昼夜节律在神经系统疾病中被破坏，大脑随着时间的推移逐渐受损，称为神经退行性疾病。这些疾病包括阿尔茨海默氏病，它是全世界痴呆症的最常见原因，也是导致死亡的主要原因。阿尔茨海默病会导致睡眠和昼夜节律的改变。这些变化可能发生在其他症状之前，可以帮助我们识别那些将患上这些疾病的人。早期诊断至关重要，因为它可以在大脑损伤过于广泛之前进行治疗。越来越多的证据表明，异常的睡眠和昼夜节律可能是导致阿尔茨海默病的部分原因。我们不知道为什么会出现异常的睡眠和昼夜节律，它们如何随时间变化，或者从长远来看它们与认知有何关系。目前尚不清楚昼夜节律紊乱是否是疾病的早期征兆，或者它们是否先于并导致神经退行性疾病。为了回答这些问题，我们必须详细分析睡眠和昼夜节律。床垫下放置的床垫和被称为体动记录仪的磨损设备使我们能够密切监测患者家中的睡眠和昼夜节律。控制睡眠和昼夜节律的基因和促进睡眠的化学物质可以在血液和脊髓液中检测到。先进的脑成像、血液和脊髓液分析使我们能够检测大脑损伤和神经退行性疾病的迹象。医学研究委员会国家健康与发展调查 (NSHD) 提供了一个独特的机会来检查异常睡眠和昼夜节律的影响关于认知和神经退行性疾病。该研究对 1946 年同一周出生的 5362 名英国人进行了跟踪调查，并定期对他们的一生进行问卷调查。 Insight 46 研究已经招募了另外 872 名来自 NSHD 的人，以进行先进的脑成像、详细的认知评估、体动记录仪、基因测试，并对他们的血液和脊髓液进行采样，以分析神经退行性变的证据。 250 人将接受重复评估，其中 100 人将接受至少 6 个月的床垫分析。这些重复和长期的评估可以特别详细地检查睡眠和昼夜节律随时间的变化，以及它们与认知、脑成像以及血液或脊髓液的渐进变化的关系。我们还将检查 375 名参与者脊髓液中控制睡眠和昼夜节律的化学物质，并检查控制睡眠或使您更容易患阿尔茨海默病的基因如何与睡眠、昼夜节律和神经退行性疾病迹象相关。晚年。 Insight 46 中五分之一的人已经出现阿尔茨海默病的早期症状。在我的博士学位中，我计划研究睡眠和昼夜节律与认知和神经退行性疾病之间的关系。我将使用从出生到七十岁的睡眠和昼夜节律问卷数据以及来自体动记录仪和床垫的睡眠数据，以无与伦比的细节检查人类一生中的睡眠和昼夜节律。将其与从 Insight 46 收集的先进脑成像、认知、血液和脊髓液数据相结合，将使我能够探索睡眠和昼夜节律与认知和神经退行性疾病之间的关系。最后，我将研究这个过程是如何由我们的基因和促进睡眠的化学物质控制的，以及这个控制系统的失败是否与认知和神经退行性疾病有关。