Sleep Spindle Dynamics as a Clinical Biomarker of Aging, Alzheimer's Disease, and Trisomy 21

睡眠纺锤体动力学作为衰老、阿尔茨海默病和 21 三体症的临床生物标志物

• 批准号: 10733629
• 负责人: Uri Tzvi Eden
• 金额: $ 257.69万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733629
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer’s disease biomarker; Biological Markers; Brain; Brain region; Clinical; Complex; Coupling; Data; Databases; Detection; Disease; Down Syndrome; Electroencephalography; Event; Functional disorder; General Population; Generations; Heterogeneity; Individual; Legal patent; Link; Mathematics; Mental disorders; Methods; Modeling; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurologic; Pathologic; Pathologic Processes; Pathology; Patients; Phase; Phenotype; Play; Polysomnography; Population; Process; Property; Recording of previous events; Research; Role; Schizophrenia; Sleep; Sleep Disorders; Specificity; Stage II Sleep; Symptoms; Time; Variant; Waxes; Work; autism spectrum disorder; biomarker development; biomarker identification; clinical biomarkers; cohort; comparison group; developmental disease; insight; memory consolidation; mild cognitive impairment; multi-ethnic; neurophysiology; non rapid eye movement; novel marker; novel strategies; older patient; sleep spindle; theories; trait

PROJECT SUMMARY Nearly every psychiatric, neurodegenerative, and neurodevelopmental disorder has sleep dysfunction as a symptom. However, the specificity of biomarkers of sleep dysfunction for a given disease process is poorly un- derstood, due to the extreme heterogeneity observed within healthy populations and clinical cohorts. Of particular importance to neurological biomarker identification are sleep spindles—waxing-waning EEG waveforms of ~15Hz oscillatory activity that define NREM Stage 2 (N2) sleep. Spindle activity has been linked to memory consolidation during sleep and associated with numerous psychiatric, neurodegenerative, and neurodevelop- mental diseases, including Alzheimer's disease, trisomy 21, schizophrenia, and autism, as well as with natural aging. Recent work has shown that spindles have trait-like intrasubject stability, but also vast intersubject heter- ogeneity—the extent of which has yet to be characterized. Without characterizing spindle variability, we cannot understand the specificity of sleep EEG biomarkers. In this study, we develop a robust mathematical framework for understanding spindle temporal dynamics. Using this framework, we will characterize the variability in spindle activity across a multi-ethnic, heterogenous population of thousands of subjects across a wide age range. We will then use these normative distributions to evaluate the specificity of established and novel biomarkers of spindle dysfunction in trisomy 21 and Alzheimer's disease and mild cognitive impairment cohorts. In doing so, we fill an important gap essential to Alzheimer's disease biomarker development, providing a context and spec- ificity lacking in current approaches.

项目总结