Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention

对麻醉药的神经生理学抵抗力低是临床前/前驱阿尔茨海默病和神经血管病理学、谵妄风险和注意力不集中的标志

• 批准号: 10870632
• 负责人: Miles Berger
• 金额: $ 33.63万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10870632
• 关键词: Administrative Supplement; Agitation; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Amyloid beta-Protein; Anesthesia procedures; Anesthetics; Antibodies; Attention; Biological Assay; Biological Markers; Brain; Brain Pathology; Clinical; Cognitive; Data; Delirium; Dementia; Dementia with Lewy Bodies; Development; Disease; Dissociation; Dose; Elderly; Electroencephalography; Fluorescence Spectroscopy; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Grant; Incidence; Knowledge; Lewy Bodies; Lewy Body Dementia; Magnetic Resonance Imaging; Measures; Monitor; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurologic; Operative Surgical Procedures; Outcome; Parents; Parietal; Participant; Pathologic; Pathology; Patients; Pattern; Perioperative; Phase; Process; Proteins; Publishing; Research Project Grants; Resistance; Risk; Sampling; Severities; Specificity; Stress Tests; Structure; Target Populations; Techniques; Work; aging brain; alpha synuclein; amyloid pathology; human old age (65+); inattention; indexing; neurocognitive disorder; neuroimaging; neuropathology; neurophysiology; neurovascular; older patient; postoperative delirium; pre-clinical; prodromal Alzheimer' s disease; response; synuclein; tau Proteins; tau-1

SUMMARY In the parent R01 research project entitled "Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention," we are examining whether - neurodegenerative disease-type changes in brain structure and activity, predispose patients to show altered brain activity changes in response to anesthetic drugs provided during surgery. This R01 project exploits the idea that altered brain activity in response to anesthetic drugs reflects an unhealthy brain, which may have latent signs of pre-clinical AD and which may indicate an increased risk of POD. The expected outcome of the R01 project is to understand better the mechanisms underlying intraoperative brain EEG responses to anesthetic drugs, postoperative delirium, Alzheimer s Disease and related dementias, and relationships between these entities. In this Administrative Supplement application, we propose to investigate the relationship between preclinical/ prodromal Lewy body dementia (LBD) pathology (ie altered forms of a protein called alpha synuclein) . It has been well established that patients with delirium and dementia display similar EEG abnormalities in pre-alpha/theta frequencies and dominant frequency overall, similar to patients with LBD. Thus, EEG activity patterns during anesthesia may be able to serve as an indicator -Synuclein levels, which might help to identify at risk patients for further workup for LBD, AD, and other related dementias.2-4

概括 在父母的R01研究项目中，标题为“对麻醉剂的神经生理性抗性低作为标志 临床前/阿尔茨海默氏病和神经血管病理学，ir妄风险和注意力不集中，“我们是 检查 - 神经退行性疾病类型是否在大脑中变化 结构和活性，患者易患麻醉药物的脑活动变化发生变化 手术期间提供。这个R01项目利用了因麻醉而改变大脑活动的想法 药物反映了不健康的大脑，可能具有临床前AD的潜在迹象，这可能表明 豆荚的风险增加。 R01项目的预期结果是更好地了解机制 潜在的术中大脑脑电图对麻醉药，术后del妄，阿尔茨海默氏病的反应 和相关的痴呆症以及这些实体之间的关系。 在此行政补充申请中，我们建议调查临床前/ 前列前路易斯身体痴呆（LBD）病理学（即改变形式的蛋白质形式称为α突触核蛋白） 。已经有很好的确定，患有ir妄的患者 痴呆症在α/theta前频率和总体上显性频率中显示出相似的脑电图异常， 类似于LBD患者。因此，麻醉期间的脑电图活动模式可能能够充当 指标 - 核蛋白水平，这可能有助于识别在风险患者中以进一步检查LBD，AD， 和其他相关痴呆2-4