Remote Ischemic Perconditioning and 90-Day Cognitive Outcomes After Acute Ischemic Stroke: A REMOTE-CAT Substudy

Background: Remote ischemic perconditioning (RIperC) is a simple, noninvasive neuroprotective strategy based on brief cycles of limb ischemia-reperfusion during cerebral ischemia. REMOTE-CAT suggested a potential functional benefit of prehospital RIperC in acute ischemic stroke. However, its effect on poststroke cognitive outcomes, which may not be fully captured by global disability scales, remains uncertain. Methods: We performed an exploratory cognitive substudy of the multicenter, randomized, double-blind, sham-controlled REMOTE-CAT trial. Patients with suspected acute ischemic stroke within 8 hours, prestroke modified Rankin Scale score <3, and RACE motor score >0 were randomized prehospital to RIperC or sham. RIperC consisted of five 5-minute cuff inflation-deflation cycles during ambulance transfer. At 90 days, patients from one center underwent a standardized neuropsychological battery assessing five cognitive domains. Results: Among 122 patients in the primary analysis, 58 (47.5%) completed neuropsychological assessment: 26 allocated to RIperC and 32 to sham. No statistically significant between-group differences were observed in domain-specific Z scores. Cognitive impairment in at least one domain was numerically less frequent with RIperC than sham (26.9% versus 34.4%). Impairment in more than one domain was also less frequent with RIperC (7.7% versus 21.9%), although the overall distribution of impaired domains did not differ significantly between groups (P=0.244). The largest domain-specific difference was observed for visual memory impairment (3.8% versus 21.9%). Conclusions: In this exploratory substudy, prehospital RIperC did not significantly improve 90-day cognitive outcomes after acute ischemic stroke. Nevertheless, RIperC-treated patients showed numerically favorable trends, particularly in global cognitive burden and visual memory. These hypothesis-generating findings support incorporating standardized cognitive outcomes in future ischemic conditioning trials.