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Many studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment. 237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls. Dysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA. This profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients.

\"Reviewing the state of the science in a dynamic, thriving field, this influential handbook integrates knowledge from multiple psychological subdisciplines. Foremost experts address the neurobiological and cognitive bases of emotion regulation and examine how individuals develop and use regulatory strategies across the lifespan. The social context of emotion regulation is explored, as are personality processes and individual differences. Critical implications are discussed for psychopathology, psychosocial interventions, and health. Including helpful cross-referencing among chapters, the volume describes cutting-edge methods and identifies promising directions for future investigation. New to This Edition *Incorporates significant scientific advances and many new topics. *Greatly expanded coverage of clinical issues and applications. *Chapters on neural systems, delay of gratification, decision making, and health. *Chapters on adolescence, social baseline theory, and desire regulation, plus more\"-- Provided by publisher.

Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12–20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1–18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45–5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86–3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35–0·63]; p<0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference −33·6% [95% CI −45·3 to −21·8], p<0·00031). Median overall survival was 12·2 months (95% CI 9·7–16·0, 69 deaths) for SRS and 11·6 months (9·9–18·0, 67 deaths) for WBRT (HR 1·07 [95% CI 0·76–1·50]; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths. Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population. National Cancer Institute.

ObjectiveTo better concurrently address emotional and neuropsychological symptoms common in veterans with comorbid post-traumatic stress disorder (PTSD) and history of traumatic brain injury (TBI), we integrated components of compensatory cognitive training from the Cognitive Symptom Management and Rehabilitation Therapy (CogSMART) programme into cognitive processing therapy (CPT) for PTSD to create a hybrid treatment, SMART-CPT (CogSMART+CPT). This study compared the efficacy of standard CPT with SMART-CPT for treatment of veterans with comorbid PTSD and history of TBI reporting cognitive symptoms.MethodsOne hundred veterans with PTSD, a history of mild to moderate TBI and current cognitive complaints were randomised and received individually delivered CPT or SMART-CPT for 12 weeks. Participants underwent psychological, neurobehavioural and neuropsychological assessments at baseline, on completion of treatment and 3 months after treatment.ResultsBoth CPT and SMART-CPT resulted in clinically significant reductions in PTSD and postconcussive symptomatology and improvements in quality of life. SMART-CPT resulted in additional improvements in the neuropsychological domains of attention/working memory, verbal learning/memory and novel problem solving.ConclusionSMART-CPT, a mental health intervention for PTSD, combined with compensatory cognitive training strategies, reduces PTSD and neurobehavioural symptoms and also provides added value by improving cognitive functioning.

Early cognitive intervention is the only routine therapeutic approach used for amelioration of intellectual deficits in individuals with Down's syndrome, but its effects are limited. We hypothesised that administration of a green tea extract containing epigallocatechin-3-gallate (EGCG) would improve the effects of non-pharmacological cognitive rehabilitation in young adults with Down's syndrome. We enrolled adults (aged 16–34 years) with Down's syndrome from outpatient settings in Catalonia, Spain, with any of the Down's syndrome genetic variations (trisomy 21, partial trisomy, mosaic, or translocation) in a double-blind, placebo-controlled, phase 2, single centre trial (TESDAD). Participants were randomly assigned at the IMIM-Hospital del Mar Medical Research Institute to receive EGCG (9 mg/kg per day) or placebo and cognitive training for 12 months. We followed up participants for 6 months after treatment discontinuation. We randomly assigned participants using random-number tables and balanced allocation by sex and intellectual quotient. Participants, families, and researchers assessing the participants were masked to treatment allocation. The primary endpoint was cognitive improvement assessed by neuropsychologists with a battery of cognitive tests for episodic memory, executive function, and functional measurements. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01699711. The study was done between June 5, 2012, and June 6, 2014. 84 of 87 participants with Down's syndrome were included in the intention-to-treat analysis at 12 months (43 in the EGCG and cognitive training group and 41 in the placebo and cognitive training group). Differences between the groups were not significant on 13 of 15 tests in the TESDAD battery and eight of nine adaptive skills in the Adaptive Behavior Assessment System II (ABAS-II). At 12 months, participants treated with EGCG and cognitive training had significantly higher scores in visual recognition memory (Pattern Recognition Memory test immediate recall, adjusted mean difference: 6·23 percentage points [95% CI 0·31 to 12·14], p=0·039; d 0·4 [0·05 to 0·84]), inhibitory control (Cats and Dogs total score, adjusted mean difference: 0·48 [0·02 to 0·93], p=0·041; d 0·28 [0·19 to 0·74]; Cats and Dogs total response time, adjusted mean difference: −4·58 s [–8·54 to −0·62], p=0·024; d −0·27 [–0·72 to −0·20]), and adaptive behaviour (ABAS-II functional academics score, adjusted mean difference: 5·49 [2·13 to 8·86], p=0·002; d 0·39 [–0·06 to 0·84]). No differences were noted in adverse effects between the two treatment groups. EGCG and cognitive training for 12 months was significantly more effective than placebo and cognitive training at improving visual recognition memory, inhibitory control, and adaptive behaviour. Phase 3 trials with a larger population of individuals with Down's syndrome will be needed to assess and confirm the long-term efficacy of EGCG and cognitive training. Jérôme Lejeune Foundation, Instituto de Salud Carlos III FEDER, MINECO, Generalitat de Catalunya.

Acute illness requiring hospitalization frequently is a sentinel event leading to long-term disability in older people. Prolonged bed rest increases the risk of developing cognitive impairment and dementia in acutely hospitalized older adults. Exercise protocols applied during acute hospitalization can prevent functional decline in older patients, but exercise benefits on specific cognitive domains have not been previously investigated. We aimed to assess the effects of a multicomponent exercise intervention for cognitive function in older adults during acute hospitalization. We performed a secondary analysis of a single-blind randomized clinical trial (RCT) conducted from February 1, 2015, to August 30, 2017 in an Acute Care of the Elderly (ACE) unit in a tertiary public hospital in Navarre (Spain). 370 hospitalized patients (aged ≥75 years) were randomly allocated to an exercise intervention (n = 185) or a control (n = 185) group (usual care). The intervention consisted of a multicomponent exercise training program performed during 5-7 consecutive days (2 sessions/day). The usual care group received habitual hospital care, which included physical rehabilitation when needed. The main outcomes were change in executive function from baseline to discharge, assessed with the dual-task (i.e., verbal and arithmetic) Gait Velocity Test (GVT) and the Trail Making Test Part A (TMT-A). Changes in the Mini Mental State Examination (MMSE) test and verbal fluency ability were also measured after the intervention period. The physical exercise program provided significant benefits over usual care. At discharge, the exercise group showed a mean increase of 0.1 m/s (95% confidence interval [CI], 0.07, 0.13; p < 0.001) in the verbal GVT and 0.1 m/s (95% CI, 0.08, 0.13; p < 0.001) in the arithmetic GVT over usual care group. There was an apparent improvement in the intervention group also in the TMT-A score (-31.1 seconds; 95% CI, -49.5, -12.7 versus -3.13 seconds; 95% CI, -16.3, 10.2 in the control group; p < 0.001) and the MMSE score (2.10 points; 95% CI, 1.75, 2.46 versus 0.27 points; 95% CI, -0.08, 0.63; p < 0.001). Significant benefits were also observed in the exercise group for the verbal fluency test (mean 2.16 words; 95% CI, 1.56, 2.74; p < 0.001) over the usual care group. The main limitations of the study were patients' difficulty in completing all the tasks at both hospital admission and discharge (e.g., 25% of older patients were unable to complete the arithmetic GVT, and 47% could not complete the TMT-A), and only old patients with relatively good functional capacity at preadmission (i.e., Barthel Index score ≥60 points) were included in the study. An individualized, multicomponent exercise training program may be an effective therapy for improving cognitive function (i.e., executive function and verbal fluency domains) in very old patients during acute hospitalization. These findings support the need for a shift from the traditional (bedrest-based) hospitalization to one that recognizes the important role of maintaining functional capacity and cognitive function in older adults, key components of intrinsic capacity. ClinicalTrials.gov Identifier: NCT02300896.

Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n =12) or placebo (placebo; n =12) in a double-blind randomized design 1 h and a half before the test. The same number of HC ( n =12) performed the SPST without receiving any medication. Each volunteer participated in only one experimental session in a double-blind procedure. Subjective ratings on the Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) and physiological measures (blood pressure, heart rate, and skin conductance) were measured at six different time points during the SPST. The results were submitted to a repeated-measures analysis of variance. Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group as assessed with the VAMS. The SSPS-N scores evidenced significant increases during the testing of placebo group that was almost abolished in the CBD group. No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS. The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD, resulting in a similar response as the HC.

The efficacy of vortioxetine 10 and 20 mg/d vs. placebo on cognitive function and depression in adults with recurrent moderate-to-severe major depressive disorder (MDD) was evaluated. Patients (18–65 yr, N = 602) were randomized (1:1:1) to vortioxetine 10 or 20 mg/d or placebo for 8 wk in a double-blind multi-national study. Cognitive function was assessed with objective neuropsychological tests of executive function, processing speed, attention and learning and memory, and a subjective cognitive measure. The primary outcome measure was change from baseline to week 8 in a composite z-score comprising the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test (RAVLT) scores. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). In the pre-defined primary efficacy analysis, both doses of vortioxetine were significantly better than placebo, with mean treatment differences vs. placebo of 0.36 (vortioxetine 10 mg, p < 0.0001) and 0.33 (vortioxetine 20 mg, p < 0.0001) on the composite cognition score. Significant improvement vs. placebo was observed for vortioxetine on most of the secondary objectives and subjective patient-reported cognitive measures. The differences to placebo in the MADRS total score at week 8 were −4.7 (10 mg: p < 0.0001) and −6.7 (20 mg: p < 0.0001). Path and subgroup analyses indicate that the beneficial effect of vortioxetine on cognition is largely a direct treatment effect. No safety concern emerged with vortioxetine. Vortioxetine significantly improved objective and subjective measures of cognitive function in adults with recurrent MDD and these effects were largely independent of its effect on improving depressive symptoms.

ObjectiveIn multiple sclerosis (MS), MRI measures at the whole brain or regional level are only modestly associated with disability, while network-based measures are emerging as promising prognostic markers. We sought to demonstrate whether data-driven patterns of covarying regional grey matter (GM) volumes predict future disability in secondary progressive MS (SPMS).MethodsWe used cross-sectional structural MRI, and baseline and longitudinal data of Expanded Disability Status Scale, Nine-Hole Peg Test (9HPT) and Symbol Digit Modalities Test (SDMT), from a clinical trial in 988 people with SPMS. We processed T1-weighted scans to obtain GM probability maps and applied spatial independent component analysis (ICA). We repeated ICA on 400 healthy controls. We used survival models to determine whether baseline patterns of covarying GM volume measures predict cognitive and motor worsening.ResultsWe identified 15 patterns of regionally covarying GM features. Compared with whole brain GM, deep GM and lesion volumes, some ICA components correlated more closely with clinical outcomes. A mainly basal ganglia component had the highest correlations at baseline with the SDMT and was associated with cognitive worsening (HR=1.29, 95% CI 1.09 to 1.52, p<0.005). Two ICA components were associated with 9HPT worsening (HR=1.30, 95% CI 1.06 to 1.60, p<0.01 and HR=1.21, 95% CI 1.01 to 1.45, p<0.05). ICA measures could better predict SDMT and 9HPT worsening (C-index=0.69–0.71) compared with models including only whole and regional MRI measures (C-index=0.65–0.69, p value for all comparison <0.05).ConclusionsThe disability progression was better predicted by some of the covarying GM regions patterns, than by single regional or whole-brain measures. ICA, which may represent structural brain networks, can be applied to clinical trials and may play a role in stratifying participants who have the most potential to show a treatment effect.