The Role of Impaired Neurobehavioral Alertness in Cognitive Decline and Alzheimer’s Disease Pathology

神经行为警觉性受损在认知能力下降和阿尔茨海默病病理学中的作用

• 批准号: 10662040
• 负责人: David T Plante
• 金额: $ 76.52万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662040
• 关键词: Acceleration; Address; Adult; Affect; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Area; Biological; Blood; Blood specimen; Cognition; Cognitive; Cohort Studies; Collection; Data; Data Set; Dementia; Disease; Disease Progression; Drowsiness; Early identification; Elderly; Epidemic; Excessive Daytime Sleepiness; Future; Genetic; Health; Hypoxia; Impaired cognition; Impairment; Individual; Investigation; Light; Link; Longitudinal Studies; Longitudinal cohort; Measures; Meta-Analysis; National Institute on Alcohol Abuse and Alcoholism; Natural History; Nature; Nerve Degeneration; Neurocognitive; Neuropsychology; Obstructive Sleep Apnea; Outcome; Participant; Pathologic; Persons; Phosphorylation; Populations at Risk; Positioning Attribute; Prevention strategy; Public Health; Recording of previous events; Research; Risk; Role; Sampling; Severities; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Fragmentations; Sleep disturbances; Statistical Models; Structural defect; Testing; Therapeutic; Time; Wisconsin; aging population; alertness; apolipoprotein E-4; clinical phenotype; cognitive function; cohort; design; disorder prevention; experience; human old age (65+); improved; inter-individual variation; middle age; modifiable risk; nervous system disorder; neurobehavioral; neurofilament; novel strategies; progression risk; prospective; sleep abnormalities; social; targeted treatment; tau Proteins; tau-1; treatment strategy; vigilance

PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD) is a debilitating neurological disorder, and soon will reach epidemic proportions in the context of an aging population. There is a clear need to identify persons at risk for AD pathology, so that preventative strategies can be developed and implemented. Multiple emerging lines of research demonstrate that sleep disturbance, and particularly excessive daytime sleepiness and obstructive sleep apnea (OSA), both increase the risk for AD pathology and dementia. Excessive daytime sleepiness is an important clinical phenotype of OSA, with individuals with impaired alertness – a function (and salient manifestation) of excessive sleepiness – experiencing more severe sequelae. Preliminary studies from our investigative team demonstrate that diminished daytime alertness measured by the psychomotor vigilance task (PVT) is specifically related to AD pathology and cognition, and that OSA moderates relationships between impaired alertness, AD pathology, and neurocognitive function. This project will advance this vital research area by leveraging emerging Alzheimer's disease biomarkers that can be detected in blood with the wealth of unique sleep data available in the Wisconsin Sleep Cohort (WSC) Study. The WSC has followed participants since the late 1980s, and is the only longitudinal cohort with stored biospecimens, sleep, PVT, and neurocognitive data spanning decades to elucidate the relationships of daytime alertness and OSA with AD pathology and cognitive decline. This investigation will prospectively collect additional blood specimens, PVT, and neurocognitive data in a targeted sample of 450 WSC participants who are now older aged, to address three Specific Aims with testable hypotheses supported by preliminary data. First, it will determine if impaired neurobehavioral alertness is associated with higher levels of pathological phosphorylated tau. Second, it will determine whether impaired neurobehavioral alertness is associated with more severe markers of neurodegeneration. Third, it will determine if impaired neurobehavioral alertness is associated with longitudinal cognitive trajectory. For all Aims, it is hypothesized that OSA moderates relationships between daytime alertness and AD pathology and cognitive decline. Detailed sleep and health history data available in the WSC importantly allows for many key covariates to be included in statistical models used for hypothesis testing. Addressing the Specific Aims of this application will have a sizeable impact on AD and sleep research, by linking a readily obtained objective measure of neurobehavioral alertness to longitudinal risk of AD pathology and cognitive decline. In so doing, this project will ultimately lead to improved preventative and therapeutic strategies that target sleep and alertness as modifiable risk factors for Alzheimer's disease.

项目摘要/摘要 阿尔茨海默氏病（AD）是一种使人衰弱的神经系统疾病，很快将达到流行病的比例 人口老龄化的背景。显然需要识别有AD病理风险的人，以便 可以制定和实施预防策略。多个新兴研究线证明了 这种睡眠障碍，尤其是白天嗜睡和阻塞性睡眠呼吸暂停（OSA） 增加AD病理和痴呆症的风险。白天过度嗜睡是重要的临床 OSA的表型，具有警觉性受损的个体 - 功能（和显着表现） 过度嗜睡 - 经历更严重的后遗症。我们调查团队的初步研究 证明通过精神运动警惕任务（PVT）衡量的白天警觉性降低是 与AD病理学和认知特别相关，OSA调节了受损之间的关系 警觉性，AD病理和神经认知功能。该项目将通过 利用新兴的阿尔茨海默氏病生物标志物可以在血液中检测到具有独特的财富 威斯康星州睡眠队列（WSC）研究中可用的睡眠数据。自WSC以来一直关注参与者 1980年代后期，是唯一具有储存生物测量，睡眠，PVT和神经认知数据的纵向队列 跨越数十年来阐明白天警觉性和OSA与广告病理学的关系 认知能力下降。这项投资可能会收集其他血标本，Pvt和 现在年龄较大的450个WSC参与者的目标样本中的神经认知数据，以解决三个 具有初步数据支持的可检验的假设的具体目的。首先，它将确定是否受损 神经行为警觉性与较高水平的病理磷酸化tau有关。其次，它将 确定神经行为警觉性受损是否与更严重的标记有关 神经变性。第三，它将确定神经行为警觉性受损是否与纵向相关 认知轨迹。对于所有目的，假设OSA白天现代关系 机敏和广告病理学和认知能力下降。 WSC中可用的详细睡眠和健康历史数据 重要的是，将许多关键的协变量包括在用于假设检验的统计模型中。 解决此应用程序的具体目标将对广告和睡眠研究产生相当大的影响， 将很容易获得的神经行为警觉的客观测量与AD病理的纵向风险联系起来 和认知能力下降。这样，这个项目最终将导致预防和治疗的改进 针对睡眠和机敏性的策略是阿尔茨海默氏病的可修改风险因素。