Peripheral Tissue Biomarker for Premorten Diagnosis of Lewy Body Dementia

摘要 本补充申请将研究COVID-19对疾病严重程度的影响以及 路易体痴呆症（LBD）的诊断生物标志物影响了美国140万人。 显示痴呆症患者更容易感染COVID-19，然而，COVID-19的影响 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研究。进一步应 目前尚不清楚路易体病与COVID-19报告的症状之间的重叠程度， 嗅觉丧失和各种神经系统症状可能进一步使LBD的临床评估和诊断复杂化。 我们将通过检测LBD患者的活动性或既往COVID-19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。在我们的父R 01范围内 作为对NIH特别关注通知（NOT-NS-21-037）的回应，我们建议考虑 COVID-19状态作为我们对LBD的人类受试者研究中的生物学变量，伴随生物标志物 评估，要实现两个目标。目标1将检查COVID-19感染是否会改变疾病的严重程度 和LBD患者的进展。将对LBD患者进行当前和既往COVID-19感染检测， 接受标准化的临床评估和神经系统评估，以评估帕金森症、认知能力下降， 和神经精神症状目标2将评估诊断组织和神经影像学生物标志物的变化 在受COVID-19感染的LBD患者中。我们提出的研究将提供分子和 关于COVID-19感染对LBD临床进展的影响的神经生理学见解， 指导预防和治疗干预的目标。

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.