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Background: Preclinical studies in transgenic models of Alzheimer's disease (AD) suggest that DHP1401 has neuroprotective and memory-enhancing effects.Objective: To evaluate the efficacy and safety of DHP1401 in AD patients treated with donepezilMethods:Methods: In a double-blind study, patients with mild-to-moderate AD were randomized (1:1:1) to receive a twice daily total dose of 500 mg or 1000 mg DHP1401 or placebo for 24 weeks. Tolerability and safety were monitored at baseline and weeks 12 and 24.Results: total of 180 patients were randomized to Active 1 (500 mg: n = 62), Active 2 (1000 mg: n = 53), and control groups (n = 65) in 16 sites in Korea. There was no significant difference in the Alzheimer's Disease Assessment Scale (ADAS-cog) score, the primary efficacy endpoint, from baseline. However, in the subgroup with mild AD patients (MMSE, 20-26) who received the high dose of DHP1401 and the group that received donepezil 5 mg, the ADAS-cog scores improved. MMSE and K-TMT-e type B were significant in both active groups at week 24. The most frequently observed symptom was dizziness (2.78%), and the most commonly observed reactions were related to metabolism and nutrition disorders (5.00%). No remarkable adverse events were observed for 24 weeks.Conclusion: Although the effectiveness of DHP1401 was not proved to be superior as the primary efficacy endpoint, the secondary endpoints, MMSE and K-TMT-e type B, showed significant beneficial effects. Also, the subgroups showed that ADAS-cog scores significantly were improved. DHP1401 could be proven beneficial for the AD treatment by further clinical trials. [ABSTRACT FROM AUTHOR]

Background and Purpose: In patients with acute ischemic stroke treated with thrombectomy, additional retriever passes may increase the likelihood of recanalization, but also the risk of intracranial hemorrhage. This multicenter retrospective register study aimed to evaluate the impact of retriever passes on treatment efficacy and safety outcomes in patients treated with mechanical thrombectomy.Materials and Methods: Patients with ischemic stroke due to large artery occlusion in anterior circulation and treated with mechanical thrombectomy were enrolled. The primary efficacy outcome was a favorable functional outcome defined as modified Rankin Scale score of 0-2 at 90 days. Major safety outcome was symptomatic intracranial hemorrhage (SICH) and mortality. Multivariate logistic regression was used to analyze the impact of retriever passes on efficacy and safety outcomes.Results: Of the 472 enrolled patients, the likelihood of favorable outcome declined in patients with more than three retriever passes (44.4% in patients with three passes, 26.3% with four passes, 14.8% with five or more passes). Multivariate logistic regression analysis identified three or less passes as an independent predictor for favorable functional outcomes (OR 2.44, 95% CI 1.10-5.45, P = 0.029). More than three passes was associated with an increased risk of SICH (OR 2.24, 95% CI 1.16-4.33, P = 0.016).Conclusions: More than three retriever passes may increase the rate of recanalization, but not the likelihood of favorable functional outcomes in ischemic stroke patients treated with mechanical thrombectomy. Notably, multiple retriever passes may also increase the risk of intracranial hemorrhage.Evidence-based Medicine: Level of Evidence: Level 4, Case Series. [ABSTRACT FROM AUTHOR]

Background: Effective treatments to alleviate depression in Alzheimer's disease (AD) have been scarce.Objective: To investigate the efficacy and tolerability of escitalopram in the treatment of depression in AD.Methods: In this 12-week randomized, double-blind, placebo-controlled trial with open-label, 12-week extension, AD subjects over 50 years of age, with depression defined by Olin's provisional diagnostic criteria, were enrolled. The Cornell Scale for Depression in Dementia (CSDD), and other measures of depression and cognition were repeated.Results: 91 subjects were screened, and 84 were randomized into either the study group or placebo group (n = 42 for both groups). Twenty-four subjects (29%) were unable to finish the study, yielding a per protocol population of 60 subjects (study group: n = 27; placebo group: n = 33). At week 12, differences in measures of depression and cognition between the two groups were not statistically significant. However, exploratory analysis suggested that further research on a subset of subjects with 'definite major depression' (baseline CSDD score ≥18) is needed. The number of treatment-related adverse-events (AE) did not differ between groups (p = 0.83) and no serious treatment-related AE were observed.Conclusion: The use of escitalopram was well tolerated in depressive dementia patients. Future studies focusing on subjects with more severe levels of depression, and with more statistical power, will be needed. [ABSTRACT FROM AUTHOR]

Background& Objective: Depression frequently combines with dementia, including early-onset Alzheimer's disease (EOAD). We investigated differences in prevalence and characteristics of depressive symptoms according to dementia severity in EOAD patients.Methods: The 15-item Korean version of the Geriatric Depression Scale (GDS-15) was administered to 412 EOAD patients. Factor analysis was used to assess GDS-15 factor structure. We subdivided participants into three groups by disease severity, then compared the frequencies and scores of individual GDS-15 items and performed logistic regression analysis to assess associations between depressive symptoms and EOAD stage.Results: Factor analysis yielded three factor categories: 1) "hopelessness and ominousness" (symptoms no. 6, 8, 12, 14, 15); 2) "unhappiness and dissatisfaction" (no. 1, 3, 5, 7, 11); and 3) "monotony and lack of energy" (no. 2, 4, 9, 10, 13). Factor 2 depressive symptoms (no. 1, 5, 11) were less common in moderate EOAD. The risk of Factor 1 symptoms: no. 12 (OR, 2.04; 95% CI, 1.19-3.50; p = 0.010) and 14 (OR, 1.84; 95% CI, 1.07-3.16; p = 0.028) was higher in mild than very mild EOAD. The risk of Factor 2 symptoms: no. 9 (OR, 2.69; 95% CI, 1.08-6.71; p = 0.033) and 13 (OR, 2.12; 95% CI, 1.02-4.40; p = 0.043) was higher in moderate than mild EOAD.Conclusion: We confirmed that depressive symptoms differ according to EOAD severity. When assessing depressive symptoms related to dementia progression, we recommend focusing on "hopelessness and ominousness" in very mild EOAD and "unhappiness and dissatisfaction" in mild EOAD. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear.Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement.Results: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function.Conclusions: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research.Registration: URL: https://www.Clinicaltrials: gov. Unique identifier: NCT03284827. [ABSTRACT FROM AUTHOR]

Background: Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion.Methods: We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556.Findings: Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group.Interpretation: There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study.Funding: Jiangsu Provincial Special Program of Medical Science. [ABSTRACT FROM AUTHOR]