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Background: The net health benefit of statin use in the oldest patients remains controversial. Preclinical models and previous clinical studies have suggested statins may exhibit neuroprotective effects in stroke, however evidence in the very old remains limited. Our objective was to compare changes in functional status before and after acute ischemic stroke (AIS) between statin users and non-users in a national cohort.Methods: A patient’s first hospitalization for AIS from 04/01/11 to 12/31/2012 was selected from Medicare Part A claims. Patients with a pre-hospitalization nursing home Minimum Data Set assessment and a post-hospitalization assessment in a skilled nursing facility were included. Pre-stroke statin exposure was defined using Part D claims. Functional status was measured continuously and categorically (dependent:<20, partially dependent(PD):20-59, assisted independent(AI):60-100) using Shah’s modified Barthel Index (mBI). Multivariable logistic regression examined the association of statins with a minimum clinically important mBI decrease of 10 points among non-dependent patients.Results: Among 10,203 patients with an assessment before hospitalization, 7.2% died, and 48.7% were included (mean age: 83.6±9.6; 74.5% women). Statin use was common (36.5%), while acute treatment was infrequent (thrombolysis: 4.9%; thrombectomy: 0.1%). The distribution of functional dependence, PD, and AI shifted from 17.3%, 56.1%, and 26.7% at baseline to 49.7%, 44.4%, and 5.9% post-stroke, respectively.A consistent association with 10-point mBI decline was observed for statin exposure among all non-dependent (OR: 0.8; 95%CI: 0.7-1.0) and within strata of PD (OR:0.8; 95%CI: 0.7-1.0) and AI patients (OR: 0.8; 95%CI: 0.5-1.3). In contrast, acute treatment was more strongly associated with function in AI (OR: 0.5; 95%CI: 0.2-1.0) versus PD patients (OR: 1.0; 95%CI: 0.7-1.5).Conclusion: In this high-burden population, our results are suggestive of a possible protective association for pre-stroke statin exposure. Further research is needed to examine temporal and dose-response relationships between statin exposure and functional outcomes across diverse patient populations.