Impact of prestroke physical activity and citalopram treatment on poststroke depressive symptoms: a secondary analysis of data from the TALOS randomised controlled trial in Denmark

Objectives To investigate the association between prestroke physical activity and depressive symptoms up to 6 months after stroke and examine if citalopram treatment modified the association.Design A secondary analysis of data from the multicentre randomised controlled trial The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS).Setting and participants TALOS was conducted at multiple stroke centres in Denmark from 2013 to 2016. It enrolled 642 non-depressed patients with first-ever acute ischaemic stroke. Patients were eligible for this study if a prestroke physical activity level was assessed by the Physical Activity Scale for the Elderly (PASE).Interventions All patients were randomised to citalopram or placebo for 6 months.Outcomes Depressive symptoms 1 and 6 months after stroke measured on the Major Depression Inventory (MDI) ranging from 0 to 50.Results A total of 625 patients were included. Median (IQR) age was 69 (60–77) years, 410 (65.6%) were men, 309 (49.4 %) received citalopram and median (IQR) prestroke PASE score was 132.5 (76–197). Higher prestroke PASE quartile, compared with the lowest PASE quartile, was associated with fewer depressive symptoms both after 1 month (mean difference third quartile −2.3 (−4.2, –0.5), p=0.013, mean difference fourth quartile −2.4 (−4.3, –0.5), p=0.015) and 6 months after stroke (mean difference third quartile −3.3 (−5.5, –1.2), p=0.002, mean difference fourth quartile −2.8 (−5.2, –0.3), p=0.027). There was no interaction between citalopram treatment and prestroke PASE score on poststroke MDI scores (p=0.86).Conclusions A higher prestroke physical activity level was associated with fewer depressive symptoms 1 and 6 months after stroke. Citalopram treatment did not seem to modify this association.Trial registration numbers NCT01937182 (ClinicalTrials.gov) and 2013-002253-30 (EUDRACT)

Exploring vascular contributions to cognitive impairment and dementia (ENIGMA): protocol for a prospective observational study

Abstract Background Post-stroke cognitive impairment (PSCI) is common. However, the underlying pathophysiology remains largely unknown. Understanding the role of microvascular changes and finding markers that can predict PSCI, could be a first step towards better screening and management of PSCI. Capillary dysfunction is a pathological feature of cerebral small vessel disease and may play a role in the mechanisms underlying PSCI. Extracellular vesicles (EVs) are secreted from cells and may act as disease biomarkers. We aim to investigate the role of capillary dysfunction in PSCI and the associations between EV characteristics and cognitive function one year after acute ischemic stroke (AIS) and transient ischemic attack (TIA). Methods The ENIGMA study is a single-centre prospective clinical observational study conducted at Aarhus University Hospital, Denmark. Consecutive patients with AIS and TIA are included and followed for one year with follow-up visits at three and 12 months. An MRI is performed at 24 h and 12 months follow-up. EV characteristics will be characterised from blood samples drawn at 24 h and three months follow-up. Cognitive function is assessed three and 12 months after AIS and TIA using the Repeatable Battery for the Assessment of Neuropsychological Status. Discussion Using novel imaging and molecular biological techniques the ENIGMA study will provide new knowledge about the vascular contributions to cognitive decline and dementia. Trial registration The study is retrospectively registered as an ongoing observational study at ClinicalTrials.gov with the identifier NCT06257823

Remote Ischemic Conditioning for Acute Stroke:The RESIST Randomized Clinical Trial

IMPORTANCE: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke.OBJECTIVE: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke.DESIGN, SETTING, AND PARTICIPANTS: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023).INTERVENTION: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants.MAIN OUTCOMES AND MEASURES: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke.RESULTS: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group.CONCLUSIONS AND RELEVANCE: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03481777.</p