Exhaled volatile organic compounds, phospho-tau and postoperative delirium

呼出的挥发性有机化合物、磷酸tau和术后谵妄

• 批准号: 10732133
• 负责人: Patrick Finan
• 金额: $ 44.41万
• 依托单位: UNIVERSITY OF VIRGINIA
• 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 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10732133
• 关键词: Acceleration; Address; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Anesthesia procedures; Beds; Biological Markers; Blood; Brain; Brain Injuries; Chemicals; Clinical; Cognitive; Complex; Complication; Delirium; Dementia; Detection; Devices; Diagnosis; Disease; Early Diagnosis; Elderly; Enzyme-Linked Immunosorbent Assay; Equipment; Excision; Exhalation; Functional disorder; Gas Chromatography; Gases; Harvest; Hospitalization; Impaired cognition; Incidence; Individual; Intervention; Life; Light; Measures; Metabolic; Metabolic Pathway; Metabolic dysfunction; Methods; Minor; Modeling; Monitor; Morbidity - disease rate; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurons; Operative Surgical Procedures; Outcome; Pathologic; Patient-Focused Outcomes; Patients; Pattern; Perioperative; Phase; Play; Postoperative Period; Precision therapeutics; Predictive Value; Process; Proteins; Research; Risk; Risk Factors; Role; Senile Plaques; Sensory; Severities; Site; Spine surgery; Stratification; Syndrome; Testing; Time; amyloid peptide; confusion assessment method; data analysis pipeline; denoising; drug development; extracellular; feature extraction; high risk; human old age (65+); hyperphosphorylated tau; improved; improved outcome; mortality; neurofilament; neuroinflammation; neuropathology; neurotoxicity; older patient; patient screening; point of care; portability; postoperative delirium; rapid detection; real time monitoring; recruit; tau Proteins; tau-1; tool; volatile organic compound

Postoperative delirium (POD) is common, especially in elderly patients. Patients with Alzheimer’s disease (AD) or AD-related dementias (ADRD) have a higher risk of delirium. Patients with delirium have a higher chance to develop AD and ADRD. It has been shown that AD-related biomarkers, such as phospho-tau and neurofilament light, in the blood are associated with POD. However, these tests take time and are expensive to perform. Harvesting blood carries a minor risk. Patients with AD and POD have metabolic dysfunction. Studies have shown that there are differences in the volatile organic compounds (VOCs) in the exhaled gases between AD patients and healthy controls. Whether this situation exists between patients with POD and non-POD is not known. Evaluating exhaled VOCs is no-invasive and can be done at bed site with our equipment. We hypothesize that patients with POD have a unique pattern of exhaled VOCs and that this pattern is associated with AD-related biomarkers in the blood. To address these hypotheses, we will recruit 150 patients with spine surgery who are 65 years or older. Their exhaled gases will be analyzed by using advanced portable gas chromatography. Their blood will be used to analyze tau, phospho-tau, neurofilament light and amyloid beta peptides. The POD incidence and severity will be assessed. The VOC and blood biomarker results of patients with POD will be compared with those of patients without POD. The predicting values of VOCs and AD-related biomarkers for POD will be determined. These studies will for the first time determine whether a no-invasive and quick analysis of exhaled VOCs can be used to predict POD. The identified VOCs that contribute to the different patterns between patients with and without POD will indicate metabolic pathways that are dysfunctional. The analysis of the correlation between exhaled VOCs and AD-related biomarkers in the blood may reveal possible relationship between AD-like neuropathology and exhaled VOCs. Thus, this project may provide initial evidence for the role of VOCs in POD and AD-related neuropathology.

术后谵妄（POD）很常见，尤其是老年阿尔茨海默病患者。 疾病（AD）或 AD 相关痴呆（ADRD）患者发生谵妄的风险较高。 研究表明，与 AD 相关的生物标志物，例如 AD 和 ADRD 的发病率较高。 血液中的磷酸 tau 蛋白和神经丝光与 POD 相关。 采集血液需要时间且费用昂贵，因此患有 AD 的患者的风险较小。 研究表明POD有代谢功能障碍，挥发性有机物存在差异。 AD 患者和健康对照者呼出气体中的化合物 (VOC) 是否如此。 POD 和非 POD 患者之间存在的情况尚不清楚。 评估呼出的 VOC 尚不清楚。 无创，可以使用我们的设备在床位完成，我们勇敢地面对 POD 患者。 具有独特的呼出 VOC 模式，并且该模式与 AD 相关生物标志物相关 为了验证这些假设，我们将招募 150 名 65 岁的脊柱手术患者。 他们呼出的气体将使用先进的便携式气体进行分析。 他们的血液将用于分析 tau 蛋白、磷酸化 tau 蛋白、神经丝光和 将评估 POD 的发生率和严重程度。 将患有 POD 的患者的生物标志物结果与无 POD 的患者进行比较。 这些研究将确定 VOC 和 AD 相关生物标志物的 POD 预测值。 首次确定是否可以对呼出的 VOC 进行无创快速分析 预测 POD 所识别的 VOC 会导致患者之间的不同模式。 没有 POD 将表明代谢途径存在功能障碍。 呼出的 VOC 与血液中 AD 相关生物标志物之间可能揭示可能的关系 因此，该项目可能提供初步证据。 VOC 在 POD 和 AD 相关神经病理学中的作用。