Peripheral Tissue Biomarker for Premorten Diagnosis of Lewy Body Dementia

摘要 这项补充申请将检查新冠肺炎对疾病严重程度的影响和 影响美国140万人的路易体痴呆症(LBD)的诊断生物标记物。 研究表明，痴呆症患者更容易感染新冠肺炎，然而，新冠肺炎的疗效- 19感染对痴呆症的严重程度和进展的影响尚未得到系统的检查。更进一步说，它是 尚不清楚路易体病与新冠肺炎报告的症状之间的重叠情况，包括 嗅觉障碍和各种神经系统症状可能会使LBD的临床评估和诊断进一步复杂化。 我们将通过检测腰椎间盘突出症患者的活跃或既往新冠肺炎感染来解决这一研究问题 检查临床表现和诊断生物标志物的变化。在我们的母公司R01的范围内 并回应美国国立卫生研究院特别利益通知(NOT-NS-21-037)，我们建议考虑 新冠肺炎作为人体生物学变量的研究腰椎病及其伴随生物标志物的研究 评估，要通过两个目标来实现。目标1将检查新冠肺炎感染是否会改变疾病严重程度 与LBD患者的病情进展有关。腰椎间盘突出症患者将接受目前和以前的新冠肺炎感染检测，并 接受标准化的临床评估和神经学评估，以诊断帕金森症、认知能力下降、 和神经精神症状。AIM 2将评估诊断组织和神经成像生物标记物的变化 在受新冠肺炎感染影响的腰椎间盘突出症患者中。我们提议的研究将提供分子和 新冠肺炎感染对腰椎间盘突出症临床进展影响的神经生理学洞察，最终 指导预防性和治疗性干预的目标。

Abstract This supplemental application will examine the effects of COVID-19 on the disease severity and changes in diagnostic biomarkers of Lewy body dementia (LBD) affecting 1.4 million people in the U.S. Recent studies have shown that patients with dementia are more susceptible to COVID-19 infection, however, the effects of COVID- 19 infection on the severity and progression of dementia has yet to be systematically examined. Further, it is unclear how overlapping symptoms between Lewy body diseases and those reported for COVID-19 including anosmia and various neurological symptoms might further complicate clinical evaluation and diagnosis of LBD. We will address this research question by testing patients with LBD for active or prior COVID-19 infection and examining changes in clinical manifestations and diagnostic biomarkers. Within the scope of our parent R01 award and in response to the NIH Notice of Special Interest (NOT-NS-21-037), we propose to consider COVID-19 status as a biological variable in our human subject studies on LBD with concomitant biomarker assessments, to be accomplished in two aims. Aim 1 will examine if COVID-19 infection alters disease severity and progression in LBD patients. LBD patients will be tested for current and prior COVID-19 infection and undergo standardized clinical assessments and neurological evaluations for parkinsonism, cognitive decline, and neuropsychiatric symptoms. Aim 2 will assess changes in diagnostic tissue and neuroimaging biomarkers in LBD patients affected by COVID-19 infection. Our proposed research will provide molecular and neurophysiological insights into the effects of COVID-19 infection on clinical progression of LBD, with the ultimate goal of guiding preventative and therapeutic interventions.