Cognitive outcomes after tadalafil treatment in patients with cerebral small vessel disease: ETLAS-2 sub-study

Advances in Neurocardiology: Focus on Atrial Fibrillation.

Is rivaroxaban safer and more effective than warfarin in patients with atrial fibrillation and stroke or TIA?

BACKGROUND:White matter hyperintensities and reduced cerebral blood flow are hallmarks of cerebral small vessel disease (CSVD). We tested the feasibility of daily treatment with the vasoactive drug tadalafil in patients with CSVD and its effects on cognition and imaging markers of CSVD.METHODS:The ETLAS-2 trial (Effect of Tadalafil in Lacunar Stroke) was a randomized, placebo-controlled, double-blind, parallel phase II trial testing 3 months of daily tadalafil 20 mg versus placebo in patients with CSVD and previous stroke or transient ischemic attack. Participants were included from the Capital Region of Denmark from 2022 to 2024. Outcomes were assessed at baseline and after 3 months. A binary logistic regression model with the treatment group as a covariate was used to calculate the primary outcome of feasibility (≥90% study drug compliance). Secondary outcomes included the Montreal Cognitive Assessment, magnetic resonance imaging markers of CSVD (Standards for Reporting Vascular Changes on Neuroimaging criteria), blood pressure, and adverse events.RESULTS:We included 76 participants (20 female, mean age, 68.0±8.9 years). Seventy-one initiated treatment, and 26 of 38 participants with tadalafil were ≥90% compliant versus 31 of 33 with placebo (odds ratio, 0.13 [95% CI, 0.03–0.69]; P=0.030). There was a female preponderance in tadalafil dropouts, with 46% of females stopping treatment, compared with only 16% of males. Adverse events occurred in 76% of participants with tadalafil versus 36% with placebo (odds ratio, 5.49 [95% CI, 1.81–18.07]; P=0.001). A trend toward lower white matter hyperintensity volume at follow-up was observed in the tadalafil group in the unadjusted per-protocol analysis (relative change, 0.939 [95% CI, 0.881–1.001]; P=0.054). No differences were observed in cognition, mental well-being, or blood pressure.CONCLUSIONS:In participants with CSVD, adherence to tadalafil was significantly lower than to placebo and did not meet the prespecified compliance threshold. We observed a nonsignificant reduction in white matter hyperintensity volume after tadalafil, which warrants larger and prolonged studies with reduced tadalafil doses to explore potential benefits in CSVD.REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05173896.

Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial

Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial

PII: S0022-3476(95)70377-2

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial

Readmissions After Left Atrial Appendage Closure in Patients With Previous Ischemic Stroke or Transient Ischemic Attack

The study aimed to explore cognitive outcomes after electroconvulsive therapy (ECT) depending on which version of common single nucleotide polymorphisms the patient expressed for brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT). A total of 87 patients from the clinical ECT service in Aberdeen, Scotland, were included in the study. Cognitive function testing (using Spatial Recognition Memory task from the Cambridge Neuropsychological Test Automated Battery and Mini-Mental State Examination) and mood ratings (Montgomery-Åsberg Depression Rating Scale) were performed before ECT, after 4 treatments, at the end of ECT and 1 and 3 months after the end of treatment. These scores were compared depending on BDNF and COMT variant at each time point using the Student t test and using a time series generalized least squares random effects model. No differences were found between the val and met versions of the BDNF or COMT polymorphism in either cognitive or mood outcomes at any time point during ECT treatment or up to 3 months of follow-up. This study did not detect significant differences in cognitive or mood outcomes between patients who have the val66val or met versions of the BDNF polymorphism. Our results suggest that these polymorphisms will not be helpful in clinical practice for predicting cognitive outcomes after ECT.

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF

Post-stroke cognitive impairment and fatigue in patients with white matter hyperintensities. A prospective cohort study.

Rationale:With the development of magnetic resonance imaging (MRI) technology, most of the research tends to find that there is a significant positive correlation between white matter hyperintensities (WMHs) and cognitive dysfunction in cerebral small vessel vascular disease. In this paper, we report 2 cases of cerebral small vessel disease with significant differences in cognitive function and analyze them by multidimensional assessment using imaging technology so as to provide a methodological reference for identifying and diagnosing the causes of differences in cognitive function in cerebral small vessel disease patients.Patient concerns:Patient 1 was a 64-year-old middle-aged man who presented 10 years ago with slow reaction time, memory loss, and loss of self-care ability, and MRI suggested multiple ischemic infarct foci with cerebral white matter changes. Patient 2 was a 69-year-old middle-aged woman, who did not have any significant abnormalities in cognitive function, and imaging suggested multiple ischemic foci, infarct foci, and cerebral white matter degeneration.Diagnosis:MRI showed a large fusion of high signal in the cerebral white matter in both patients, which belonged to the category of cerebral small vessel disease according to the Fazekas classification of grade 3.Interventions:We used imaging techniques to compare the 2 MRI brain white matter high signals in a multidimensional manner and further compared the differences in cognitive functioning between the 2 in terms of brain age, brain functional networks, focal loading of white matter fiber tracts, and neuropsychological scales.Outcomes:Brain age difference was assessed by whole-brain level and brain function network, white matter fiber bundle lesion load, and Montreal Cognitive Assessment and Mini-Mental State Examination scale scores; the results suggested that patient 1 had relatively poor cognitive function.Lessons:In this paper, we concluded that the volume of high white matter signal in WMH is not positively correlated with the severity of cognitive impairment. In addition to cerebral WMHs, we believe that alterations in cerebral network connectivity and white matter microstructure may be the neuroimaging basis of cognitive decline in patients with WMH, which may provide a new idea for the early diagnosis of cognitive function in patients with cerebral small vessel disease.

Evaluation of: Diener HC, Connolly SJ, Ezekowitz MD et al.: Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 9(12), 1157–1163 (2010). This study aimed to assess the efficacy and safety of daibgatran in two doses (110 and 150 mg) compared with warfarin in a prespecified subgroup analysis of patients with previous stroke or transient ischemic attack in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. There were nonsignificant risk reductions for the primary outcome (stroke and systemic embolism) for both doses of dabigatran compared with warfarin in this subgroup of patients. However, the 110-mg dose of dabigatran provided significantly greater reductions of mortality and higher net clinical benefit compared with warfarin. This was not seen in the 150-mg dose. The bleeding complication rates of this subgroup were consistent with the main RE-LY trial. In the warfarin group, patients with previous history of stroke or transient ischemic attack developed more intracranial bleeding than patients without this history, but this was not the case in dabigatran treatment groups.

Background: One year after stroke 50-70% of survivors have information processing speed (IPS) impairment. IPS is a complex, elemental cognitive function with close but separate relationships with memory, attention, executive function, reading, and writing. IPS impairment can be devastating, even without physical deficits. Hypothesis: The frequency and severity of IPS impairment in patients with acute stroke is unrelated to stroke severity. Methods: In a longitudinal study, 30 adults with acute mild (NIHSS <5) versus moderate stroke (NIHSS 5-12) were assessed for IPS and memory impairments at three time points (< 72 hours, Week 3, and Week 12). The Symbol Digit Modalities Test (SDMT) was the primary IPS instrument, scores below the norm (51-62 points) indicate impairment. Results: Using linear mixed model regression, no significant difference was noted between patients with mild and moderate stroke in frequency and severity of IPS impairment (p=0.2). All patients had baseline abnormal SDMT scores, improving 21% by Week 12 (p=.005) with one patient scoring as unimpaired (51 points). Patients with mild stroke (n=18) had baseline scores on average 53% lower than SDMT norm (mean score 24 (12), [95% CI] 6 [18, 30], Standard Error (SEM) 3) and 32% lower at Week 12 (mean 34 (11), [95% CI] 5 [29, 40], SEM 3). Patients with moderate stroke (n=12) had baseline SDMT scores 60% lower than norm (mean 21 (11), [95% CI] 6 [15, 27], SEM 3) and 39% lower by Week 12 (mean 31 (12), [95% CI] 7 [25, 38], SEM 3). Memory impairment at enrollment (<72 hours post stroke) was noted in 100% of patients with moderate stroke and 78% of patients with mild stroke; at Week 12 the frequency of memory impairment was equal in both groups (67%). Conclusion: IPS were critically impaired, in both mild and moderate stroke, with minimal spontaneous recovery at Week 12. IPS impairment is clinically significant during stroke recovery. IPS impairment should be considered in the planning of healthcare of stroke victims even with mild stroke.

Introduction: We examined if language preference was associated with differences in neurological, functional, and cognitive stroke outcomes among Mexican Americans (MAs). Methods: Ischemic or hemorrhagic stroke patients identified from the Brain Attack Surveillance in Corpus Christi (BASIC) Project (2009-2018). Poststroke outcomes at 90 days included neurological [National Institutes of Health Stroke Scale (NIHSS) range 0-44, higher worse], functional [activities of daily living/instrumental activities of daily living (ADL/iADL) range 1-4, higher worse], and cognitive [modified Mini-Mental State Examination (3MSE) range 0-100, lower worse]. Language was determined by which language participant preferred to complete outcome interview in. Differences in stroke outcomes by language were analyzed by weighted Tobit regression. Weights (baseline and outcome interview participation) were created by logistic regression to account for attrition. Age, education, initial NIHSS score, smoking status, BMI, insurance status, sex, and comorbidities were included in weighted Tobit regression models. Results: Of 1,096 patients, 1,001 preferred English and 95 Spanish. Spanish speakers were older (72 versus 66 years; p < 0.01), received less education (p < 0.01), and had higher prevalence of atrial fibrillation (p = 0.02) than English speakers. No other significant differences in baseline demographics or clinical factors were found. In fully adjusted models (Table 1) Spanish speakers had significantly better neurological and functional but worse cognitive outcomes compared with English speakers. Conclusion: This population-based study found better neurologic and functional stroke outcomes among Spanish speaking versus English speaking MAs. The difference in the cognitive outcome may be explained, at least in part, to lack of cultural equivalence of the test instrument. These data suggest further research into the resilience observed among Spanish speakers.