Faster Thrombolysis Is Associated With Improved Cognitive Outcomes in Patients With Acute Ischemic Stroke Treated With Alteplase and Tenecteplase: A Substudy of the AcT Trial

BACKGROUND: Cognitive impairment after stroke is linked with poorer functional outcomes. Faster thrombolytic improves recanalization, 3-month functional recovery, and in-hospital survival. We examined whether faster treatment times from door-to-needle and symptom onset-to-needle (OTN) impacted cognition. METHODS: This study is a prespecified secondary observational cohort analysis of the AcT randomized clinical trial (Alteplase Compared to Tenecteplase; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249) data. Eligible participants were English-speaking individuals who independently completed the trial's primary outcome and were recruited from 18 stroke centers within Canada. Prospective cognitive outcomes were collected at 90 to 180 days using a Telephone Montreal Cognitive Assessment (T-MoCA range, 0-22; <17 impairment). The primary aim was to assess cognitive performance and its relationship with treatment times (door-to-needle and OTN) at 90 to 180 days. Linear and logistic regression analyses were used to evaluate the relationship, adjusting for treatment allocation, age, sex, baseline National Institutes of Health Stroke Scale, education, ethnicity, and occlusion location. RESULTS: Three hundred ninety-nine (50%) of 791 eligible subjects completed the T-MoCA. The mean age was 66±13 years, 38.8% were female, and the mean T-MoCA score was 16±4. Shorter OTN times (but not door-to-needle) were associated with higher T-MoCA scores on linear regression (β, -0.009 [95% CI, -0.016 to -0.002]) and with increased odds of T-MoCA impairment for every 1-minute increase on logistic regression (odds ratio, 1.005 [95% CI, 1.001-1.009]). There was no difference between the alteplase and tenecteplase subgroups in the relationship between treatment times and cognition. Each 15-minute reduction in OTN was associated with a 7.3% reduction in the probability of impairment (score <17) on the T-MoCA. CONCLUSIONS: Faster OTN time, with either alteplase or tenecteplase, was associated with higher T-MoCA scores and reduced the likelihood of impairment at 90 days. Faster thrombolytic treatment may reduce cognitive burden after stroke.