Small Strokes, Big Impact: Excessive Mortality After Acute Ischemic Stroke in Parkinson's Disease

Abstract Background Acute ischemic stroke (AIS) in those with Parkinson's disease (PD) is a growing healthcare burden but mortality studies are significantly lacking. Objective To map short‐ and long‐term survival, stratified by relevant comorbidities and stroke characteristics. Methods Individuals from the United States Veterans Health Administration were included. AIS and PD were defined by validated International Classification of Diseases (ICD) codes, pharmacy data, and encounter type. Covariates included demographics, smoking status, cardiovascular comorbidities, post‐traumatic stress disorder, traumatic brain injury, and frailty. Individuals with PD and stroke were matched 4:1 to controls and survival was measured over 10 years. Two percent of strokes were manually reviewed for size, location, and mechanism per TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Results A total of 3173 cases of PD and AIS were identified and matched to groups of PD‐only, stroke‐only, and controls (N = 12,692 each). Survival analysis showed PD‐only and stroke‐only had a predictable increased mortality (added deaths ranged from 1.9 0.9, 2.9 to 4.7 2.9, 6.6 per 100 person‐years). PD + stroke showed further increased mortality with distinct timelines at 0–1‐, 1–5‐, and 5–10‐year periods and synergy accounted for 2.9 0.5, 5.4 to 19.3 14.0, 24.6 additional deaths across 10 years. Effects persisted after matching for cardiovascular comorbidities, neurotrauma, and frailty. PD + stroke compared with stroke‐only had smaller strokes (80.0% vs. 63.2%) and no differences in location, mechanism, or recurrence rates. Conclusions Patients with PD and AIS had greater than expected mortality that was independent of comorbidities or stroke characteristics. This may reflect widespread structural and functional deficits that may warrant a targeted therapeutic strategy. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.