Pilot: Predictors and Biomarkers for VCID Versus Cognitive Recovery after Stroke Thrombectomy

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 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.