Predictors and Biomarkers for VCID versus Cognitive Recovery after Stroke Thrombectomy in Rural Appalachia

阿巴拉契亚农村地区中风血栓切除术后 VCID 的预测因子和生物标志物与认知恢复

• 批准号: 10659462
• 负责人: Jordan Patrick Harp
• 金额: $ 67.69万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659462
• 关键词: Acute; Address; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Biological; Biological Markers; Blood; Blood Proteins; Blood specimen; Brain; Caregiver Burden; Caring; Catchment Area; Characteristics; Chronic; Clinical; Coagulation Process; Cognition; Cognitive; County; Data; Dementia; Development; Early Diagnosis; Educational workshop; Enrollment; Equation; Excision; Goals; Health Services Accessibility; Home; Home visitation; Impaired cognition; Inflammation; Inflammatory; Joints; Life; Machine Learning; Measures; Mechanics; Medical History; Medical Records; Methods; Modeling; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; Outcome; Participant; Patients; Plasma; Positioning Attribute; Procedures; Proteins; Proteomics; Registries; Rehabilitation therapy; Research; Rural; Rural Appalachia; Rural Population; Sampling; Signal Pathway; Site; Statistical Models; Stroke; Stroke Belt; Suburban Population; Testing; Thrombectomy; Time; Travel; Underserved Population; United States National Institutes of Health; Validation; Venous blood sampling; Work; acute stroke; barrier to care; care delivery; cognitive impairment no dementia; cognitive performance; cognitive recovery; comorbidity; disability; follow-up; functional improvement; health care availability; health disparity; improved; medical complication; medically underserved; mortality; neurocognitive test; novel; novel marker; novel therapeutic intervention; novel therapeutics; outcome prediction; patient population; post stroke; post stroke cognitive impairment; precision medicine; predictive marker; predictive modeling; programs; prospective; protein biomarkers; protein expression; retention rate; rural counties; rural underserved; rurality; social health determinants; stroke cognitive outcome; stroke patient; success; underserved area; urban health disparities; vascular cognitive impairment and dementia

Vascular cognitive impairment and dementia (VCID) is present in 25-30% of stroke patients, and it is difficult to predict at the time of stroke who those patients will be. The National Plan to Address Alzheimer’s Disease and the NHLBI-NINDS VCID Workshop called for increased research on VCID prediction, especially in underserved populations. The proposed research will identify predictors of cognitive recovery in rural, underserved patients after mechanical thrombectomy for emergent large vessel occlusion (ELVO) stroke. These predictors will target patients that would benefit from intensive rehabilitation. Our novel biologic sample registry was used to identify proteins in systemic blood samples taken during thrombectomy as independent predictors of cognitive performance at post-stroke discharge and 90-day follow-up. The hypothesis is that these proteins will provide incremental predictive validity for cognitive impairment including dementia, over and above clinical characteristics, social determinants of health, and traditional ADRD plasma biomarkers. The proposed study will prospectively enroll 225 patients collecting systemic arterial blood at the time of thrombectomy and analyze protein expression. Using a retention strategy tailored to underserved rural participants, neurocognitive test data and venous blood samples for longitudinal protein expression will be collected from 3 months to 2 years post- thrombectomy. The study site, located in the US Stroke Belt with some of the most medically underserved rural counties in the nation, will contribute to the NIH priority focus on health disparities. Specific Aim 1: Test the hypothesis that increased patient home county rurality predicts worse cognitive outcomes post-stroke, both acutely and chronically. Generalized estimating equation models will test the main effect of home county rurality and other social determinants of health on cognitive status (normal, cognitive impairment no dementia, dementia), the main effect of time on cognitive performance across time points, and the interaction of rurality and time on cognitive status across time points. Associations among rurality, comorbidities, and time-of-thrombectomy blood protein expression will be auxiliary analyses. Specific Aim 2: Test the hypothesis that ADRD biomarkers in systemic blood at time of thrombectomy are biomarkers for acute post-stroke cognitive impairment and chronic VCID two years later. Blood samples will be assessed for known proteomic biomarkers for cognition at the UKY Biomarker Center. Specific Aim 3: Test the hypothesis that novel biomarkers in systemic blood at time of thrombectomy predict chronic VCID including dementia, over and above the effects of ADRD markers. Proteomic analysis will be conducted on time-of-thrombectomy blood samples to measure the expression of inflammatory-related proteins. Hierarchical generalized estimating equation models will assess the incremental improvement in prediction of cognitive status over time added by these addition markers. Analyses will use LASSO methods and split-sample cross-validation to create a predictive model based on both ADRD and novel biomarkers that predict cognitive outcomes.

25-30%的脑卒中患者存在血管性认知障碍和痴呆（VCID），并且很难诊断