Characterizing Alzheimer's Risk in Retired Night Shift Workers: Cognitive Function, Brain Volume, and Brain Bioenergetics

退休夜班工人患阿尔茨海默病的风险特征：认知功能、脑容量和脑生物能学

• 批准号: 10350125
• 负责人: Henry Matthew Lehrer
• 金额: $ 12.22万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10350125
• 关键词: Adenosine Triphosphate; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; Amyloid beta-Protein; Atrophic; Attenuated; Behavioral; Bioenergetics; Biological Markers; Brain; Chronic; Cicatrix; Circadian Dysregulation; Circadian Rhythms; Clinical; Cognitive; Consumption; Cornus; Data; Data Collection; Deterioration; Development; Development Plans; Early identification; Education; Elderly; Energy Metabolism; Epidemiology; Episodic memory; Ethnic Origin; Exhibits; Exposure to; Future; Glucose; Goals; Health; Hippocampus (Brain); Hour; Impaired cognition; Individual; Intervention; Knowledge; Learning; Link; Long-Term Effects; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetism; Measures; Mediating; Metabolic; Methods; Nerve Degeneration; Neurobiology; Neurocognitive; Neurons; Participant; Pathway interactions; Pattern; Peripheral; Pharmacology; Phosphocreatine; Phosphorus; Plasma; Play; Population; Prevention; Public Health; Race; Recovery; Research; Research Personnel; Risk; Rodent; Role; Sampling; Scientist; Sentinel; Sleep; Sleep disturbances; Societies; Spectrum Analysis; Structure; Testing; Training; Training Programs; Work; base; behavioral pharmacology; brain volume; career; career development; cingulate cortex; cognitive function; cognitive testing; cohort; dementia risk; design; executive function; indexing; innovation; inorganic phosphate; interest; neurogenesis; neuroimaging; poor sleep; precision medicine; predictive marker; prevent; primary outcome; programs; rehabilitation strategy; retiree; sex; shift work; skills; tau Proteins

PROJECT SUMMARY/ABSTRACT Night shift work is common in the current 24-hour global society and is increasingly recognized as a risk factor for Alzheimer’s Disease (AD) and related dementias (ADRD). However, we know very little about the persistence, recovery from, or pathways through which shift work contributes to AD/ADRD. Neuronal metabolic decline (i.e., disrupted brain bioenergetics) contributes to AD/ADRD development and progression, and the repeated sleep and circadian disruptions in shift work compromise peripheral energy metabolism. This K01 proposal will advance these findings by comparing indices of Alzheimer’s disease risk and brain bioenergetics between retired night shift workers and retired day workers. N = 40 participants (n = 20 retired night shift workers, n = 20 retired day workers) ages 65-80 from an established cohort will perform neurocognitive assessments (e.g., episodic memory, executive function) and 7 Tesla neuroimaging. Structural magnetic resonance imaging will assess hippocampal, posterior cingulate cortex, and retrosplenial cortex volume and phosphorous magnetic spectroscopy will assess brain bioenergetics, including adenosine triphosphate, phosphocreatine, and inorganic phosphate. This study will compare retired night shift workers and retired day workers on cognitive function, brain volume, and brain bioenergetics, and will examine the association of brain bioenergetics with brain volume among retired night shift workers. To conduct this research, Dr. Lehrer will pursue a program of training that will advance his knowledge and skills in the assessment of Alzheimer’s disease-related cognitive function, brain structure, and neurobiology (i.e., bioenergetics and AD-specific proteinopathy). He will also learn how to integrate these methods into his emerging program of sleep and circadian rhythm and AD/ADRD research. This training, along with findings from the proposed study, will allow Dr. Lehrer to launch his career as an independent investigator studying the role that long-term sleep and circadian disruption plays in Alzheimer’s disease to inform impactful prevention efforts for retired night shift workers. Study findings could influence our approach to AD/ADRD risk among current and former shift workers, leading to early identification of at-risk individuals at the conclusion of, or even during a career in shift work. Results will inform future studies using experimental approaches to test causal relationships, inform development and dissemination of interventions, and elucidate precision medicine approaches to prevent and attenuate the clinical course of AD/ADRD. Such interventions may include potentially modifiable behavioral (e.g., sleep and circadian rhythm enhancement) and pharmacological (e.g., bioenergetics-boosting compounds) therapies for AD/ADRD intervention and/or prevention. The proposed study will generate public health-relevant data that will help to reduce AD/ADRD risk and inform behavioral and bioenergetics-focused therapies to prevent and mitigate the clinical course of Alzheimer’s disease and related dementias among a large portion of current and former U.S. workers.

项目摘要/摘要 夜班工作在当前的24小时全球社会中很普遍，并且越来越被认为是危险因素 对于阿尔茨海默氏病（AD）和相关痴呆症（ADRD）。但是，我们对 转移工作对广告/ADRD造成的持久性，恢复或途径。神经元 代谢下降（即脑生物能扰的破坏）有助于AD/ADRD的发展和进展， 在轮班工作中反复的睡眠和昼夜节律破坏损害外周能代谢。这 K01提案将通过比较阿尔茨海默氏病风险和大脑的指标来提高这些发现 退休的夜班工人和退休的一日工工人之间的生物能学。 n = 40名参与者（n = 20退休 夜班工人，n = 20个退休的日期工人）65-80岁的队列将表演 神经认知评估（例如，情节记忆，执行功能）和7个特斯拉神经影像学。结构 磁共振成像将评估海马，后扣带回皮质和脾后皮质 体积和磷磁光谱将评估脑生物能，包括腺苷 三磷酸，磷酸磷酸盐和无机磷酸盐。这项研究将比较退休的夜班工人 以及退休的一日工人在认知功能，大脑体积和脑生物能学方面，将检查 退休的夜班工人之间的大脑生物能学与大脑体积的关联。进行此操作 研究，Lehrer博士将进行一项培训计划，以提高他的知识和技能 评估阿尔茨海默氏病相关的认知功能，大脑结构和神经生物学（即 生物能和广告特异性蛋白质病）。他还将学习如何将这些方法整合到他的 睡眠和昼夜节律和AD/ADRD研究的新兴计划。这项培训以及发现 从拟议的研究中，将允许Lehrer博士从事研究 长期睡眠和昼夜节律在阿尔茨海默氏病中发挥的作用，以告知有影响力的预防 为退休的夜班工人的努力。研究发现可能会影响我们在 当前和前任转变工人，导致在或 即使在轮班工作的职业中。结果将使用实验方法进行测试，为未来的研究提供信息 因果关系，为干预措施的发展和传播提供信息，并阐明精确医学 预防和衰减AD/ADRD的临床过程的方法。这样的干预措施可能包括 潜在的可修改行为（例如睡眠和昼夜节律增强）和药物（例如， 促进AD/ADRD干预和/或预防的生物能力增强化合物）。提议 研究将产生与公共卫生相关的数据，这将有助于降低广告/ADRD风险并为行为提供信息 以及以生物能力为中心的疗法，以预防和减轻阿尔茨海默氏病的临床过程和 当前和前美国工人的大部分痴呆症相关。