Post-stroke Cognitive Impairment and Dementia

Vascular contributions to cognitive impairment and dementia are increasingly recognized as independent causes of dementia, particularly due to their high prevalence and potential for intervention. Each year, nearly 795,000 Americans suffer a new or recurrent stroke, with one in three patients subsequently developing post-stroke cog- nitive impairment and dementia (PSCID). Despite its enormous public health impact, the accurate estimation of PSCID prevalence and the identification of associated risk factors face considerable challenges, including issues related to data quality and research methodologies. Furthermore, many stroke survivors have co-existing cardi- ovascular diseases. The extent to which additional vascular risk factors may interact with stroke in precipitating PSCID remains unclear. Importantly, pharmacological management of vascular risk factors plays a pivotal role in secondary stroke prevention. In theory, medications including antihypertensive, antithrombotics, and statin may prevent PSCID through the prevention of recurrent ischemic events, yet there is limited evidence for specific therapeutic strategies for PSCID prevention. Leveraging the nation’s largest stroke registry and Medicare data, we propose to build a real-world data platform to advance PSCID research. Using this unique data resource, which encompasses two million stroke records from over 2000 US hospitals, we will determine the incidence and prevalence of PSCID, identify associated risk factors, and potential pharmacological targets for prevention. The central hypotheses are that stroke survivors are at risk for cognitive impairment and dementia; the features of the index stroke event, in conjunction with demographics, pre-existing comorbidities, in-hospital treatment, and secondary stroke prevention may influence the risk of PSCID. The proposed research in innovative in four key ways: 1) A patient-centered approach to address a major concern for stroke survivors and their caregivers; 2) A shift in focus from selected samples in single center studies or small cohort to encompass nationwide diverse stroke populations; 3) Innovative utilization of instrumental variable analysis, which mimics a trial-type design within observational data; 4) Rapid dissemination through professional societies and patient-led initiatives. The proposed research is significant, because it addresses a high-priority area for aging research highlighted in the National Plan to Address Alzheimer’s Disease. As the number of stroke survivors living with dementia continues to increase, obtaining the incidence and prevalence of PSCID will provide a more accurate estimate of disease burden. This, in turn, will inform the development of appropriate policy and the allocation of healthcare resources. From a clinical practice perspective, knowledge gained from this study will enhance our understanding of post stroke medical management and care planning needed by stroke survivors. Importantly, since both stroke and vascular risk factors are preventable and treatable, the identification of contributing factors, particularly modifia- ble ones, will be critical for the development of personalized prevention strategies and targeted interventions aimed at alleviating the burden of cognitive impairment and dementia among stroke survivors in our aging society.