Meta-analytical and electrophysiological evidence for executive dysfunction in primary dystonia

Interaction of oxidative stress and BDNF on executive dysfunction in patients with chronic schizophrenia

Executive dysfunctions are part of the clinical symptoms of a stroke and can inhibit the process of rehabilitation. Patients with impaired executive functions may manifest aggression, impulsiveness, impaired thinking and planning. The aim of this study was to assess the effect of the ischemic focus location on the effectiveness of physiotherapy in improving the executive functions in patients after stroke. Ninety patients after unilateral ischemic cerebral stroke were studied. We studied 45 patients treated at the Department of Rehabilitation and Physical Medicine of the WAM University Hospital of Lodz for 5 weeks. The rehabilitation program included: kinesitherapy, physiotherapy, speech therapy, psychological consultations and psychotherapy. The control group consisted of patients who were waiting for admission to the Department of Rehabilitation. The patients in both groups were divided into three subgroups with different locations of stroke: front, back and subcortical. Executive functions were measured by the Wisconsin Card Sorting Test (WCST), the trail making test (TMT - A, TMT - B), the verbal fluency test (VFT). Patients rehabilitated in the hospital with the front and subcortical lesion location reported improvement in executive functions in terms of a greater number of the analyzed indicators of the Wisconsin Card Sorting Test (WCST) than those with the back lesion location. Patients rehabilitated at home with the subcortical lesion location did not experience a significant improvement in executive functions in any of the analyzed indicators of the Wisconsin Card Sorting Test (WCST). Most of the indicators, with the exception of the total errors of Wisconsin Card Sorting Test (WCST) and TMT B, have not been modified by the location of stroke. Executive dysfunction occurs not only in patients with an anterior location of the stroke, but also in the posterior and subcortical locations. Patients with a subcortical location of the stroke require more treatment to mitigate the dysfunction.

Objectives Although primary dystonia is typically characterized as a movement disorder, it is also associated with cognitive alterations in the domain of executive functioning which may arise from changes in cortico-basal ganglia circuits. Specifically, in comparison to healthy controls, patients with dystonia show deficits in neuropsychological tests of cognitive flexibility. However, it is unclear whether cognitive inflexibility is caused by the pathomechanisms underlying primary dystonia or by confounding factors such as depression or symptom-related distraction.Methods The present study aimed to eliminate these confounds by examining cognitive flexibility in dystonia patients and in patients with similar motor symptoms but without a comparable central pathophysiology. Eighteen patients with primary blepharospasm, a common form of dystonia affecting the muscles around the eyes, and 19 patients with hemifacial spasm, a facial nerve disorder causing similar eyelid spasms, completed a computerized version of the Wisconsin Card Sorting Test (cWCST). The two groups were further compared on tests of global cognitive functioning, psychiatric symptoms, health status, and impulsiveness. Results Blepharospasm patients committed significantly more errors on the cWCST than patients with hemifacial spasm. Group differences were most pronounced with regard to integration errors, a measure of rule-inference processes on the cWCST. Integration errors were also associated with impulsiveness in patients with blepharospasm. Conclusions Primary blepharospasm is related to deficits in cognitive flexibility, even when blepharospasm patients are compared with patients who suffer from motor symptoms of non-dystonic origin. Our results support the possibility that cognitive inflexibility results from the specific pathophysiological processes underlying primary dystonia. (JINS, 2016, 22, 662-670).

Background: Alcohol Use Disorder (AUD) is associated with significant cognitive impairments, particularly in executive functioning, yet evidence for cognitive rehabilitation therapy (CRT) in low-resource settings remains limited. This study evaluated the efficacy of CRT for mild executive dysfunction among male AUD patients in Zambia. Methods: A randomized controlled trial was conducted with 56 participants (aged 18-40 years) recruited from a residential rehabilitation center in Lusaka. Participants were randomized to either an 8-week CRT program (Brain Wave-R, n=28) or active control (painting sessions, n=28), both delivered alongside standard treatment. Executive function was assessed pre- and post-intervention using the Zambian Neurobehavioral Test Battery, including the Wisconsin Card Sorting Test (WCST), Colour Trails Test 2 (CTT), and Stroop Test. Results: The CRT group demonstrated significant improvements in response inhibition (Stroop Test: fewer errors, p=0.01; more words completed, p<0.01) compared to controls. However, no significant between-group differences emerged for cognitive flexibility (WCST: correct responses p=0.87; categories completed p=0.06) or task-switching (CTT: errors p=0.12; time p=0.56). Secondary analyses revealed government-employed participants showed better outcomes on WCST (p=0.04) and CTT (p=0.03), while those with chronic medical conditions performed worse on WCST (p<0.001). The control group showed unexpected but significant Stroop Test improvements (p<0.001), suggesting non-specific benefits of structured activities. Conclusion: CRT shows selective efficacy for improving response inhibition in Zambian AUD patients, with employment status and health conditions moderating treatment effects. These findings support targeted implementation of CRT in low-resource settings, particularly for patients without significant comorbidities. Future research should investigate optimal intervention duration and strategies to enhance effects on complex executive functions.

Executive dysfunction (ED) may lead to problem behaviour and impaired activities of daily living in many neuropsychiatric disorders, but the neuroanatomical correlates of ED are still not well known. Different aspects of executive functions were studied by widely used neuropsychological tests in 214 elderly patients 3 months after ischaemic stroke, and a sum score of eight different measures was counted in each patient. The number and site of brain infarcts as well as severity and location of white matter lesions (WMLs) and brain atrophy on magnetic resonance imaging were recorded and compared between patients with and without ED. ED was present in 73 (34.1%) of the 214 patients. The mean frequency of brain infarcts in the brain and in the left hemisphere was higher in the patients with ED. Lesions affecting the frontal-subcortical circuits (e.g. pallidum, corona radiata or centrum semiovale) were more frequent in patients with ED than in those without. Also, patients with pontine brain infarcts frequently had ED, but this may have been due to more extensive ischaemic changes in these patients in general. Mean number of brain infarcts affecting the pons and posterior centrum semiovale on the left side, moderate to severe medial temporal atrophy, the Fazekas white matter score, the Mini-Mental State Examination score and low education were independent correlates of ED. Brain infarcts and WML affecting the frontal-subcortical circuits or the pons may increase risk for ED in stroke patients.

P3-013: Correlations between cognitive and behavioral measures of executive dysfunction in patients with mild Alzheimer’s disease

Background:The relationship between depression, hippocampus (HC), and executive dysfunctions seems complex and has been the focus of research. Recent evidence indicates a possible role of HC in executive dysfunction seen in depression. No such studies on Indian population have been done.Aim:To look for changes in HC and executive functions in depression.Settings and Design:A cross-sectional analytical controlled study. Sample size 50 (controls 50).Materials and Methods:Hippocampal volume and executive dysfunction was measured using structural magnetic resonance imaging (MRI) and Wisconsin Card Sorting Test (WCST), respectively. Findings on these two parameters were compared between depressives and healthy matched controls as well as between first episode (FE) and recurrent depressives and across the severity of depression (mild, moderate, and severe).Statistical Analysis:Statistical Package for Social Sciences (SPSS) version 17 was used for analysis. Normally distributed continuous variables were analyzed with independent t-tests. Analysis of variance (ANOVA) was used for multiple comparisons. Categorical data were compared with χ2 or Fisher's exact test. Clinical correlations were conducted using Pearson correlations.Result:Depressed patients had a smaller left (Lt) hippocampal volume as well as poor performance on several measures of executive functions. Smaller hippocampal volume was found even in FE. Those who had a past burden of depressive illness had an even smaller hippocampal volume. No direct correlation was found between the HC volume and cognitive dysfunction.Conclusion:Depressive illness appears to be toxic to the HC. The relationship between HC and executive dysfunction in depression may be indirect through its functional connections.

Studies of adults who have been diagnosed with, and treated for, bipolar disorder have shown that these patients exhibit impairment on measures of executive functioning. However, it is unclear whether executive dysfunction precedes the diagnosis of bipolar illness, or develops subsequent to its onset. Moreover, investigators have failed to control for the effects of premorbid attentional problems on cognitive performance in these patients. The present authors explored these questions using data from a longitudinal prospective study of individuals at risk for major mood disorder. Results revealed that 67% of participants who met criteria for bipolar disorder in young adulthood showed impairment on the Wisconsin Card Sorting Test (WCST) when they were assessed during adolescence, as compared with 17% of individuals with no major mood diagnosis, and 19% with unipolar depression. This association between performance on the WCST and bipolar illness was not accounted for by high rates of premorbid attentional disturbance. In fact, among participants with early attentional problems, only those who ultimately developed bipolar disorder exhibited impairment on the WCST. Early attentional problems that preceded unipolar depression or no mood disorder were not associated with executive dysfunction.

ObjectiveLimited research exists to explain differential executive functioning impairment in clinical populations, particularly between the Wisconsin Card Sorting Task (WCST) and the Trail Making Test (TMT).MethodsThe distribution of clinical diagnoses was examined in patients failing none, one, or both tasks, and executive task performance was compared among dementia-related diagnoses. 266 participants received evaluations through an Alzheimer’s Disease Research Center, which included executive tasks. Dementia-related diagnoses were established through consensus.ResultsChi-Square analyses indicated that TMT failure, with or without WCST failure, possessed higher associations with dementia diagnoses. Repeated measures ANOVA similarly indicated that participants with dementia, especially Mild and Moderate severity, performed worse on TMT.ConclusionsExecutive dysfunction was observed in dementia-related diagnoses, and TMT failure was implicated in dementia in higher proportions than WCST impairment. TMT appears more sensitive than WCST for assessing executive impairment across diagnoses, especially when time and resources are limited in screening and clinical settings.

Catechol-O-Methyltranferase (COMT) plays a crucial role in the removal of cortical dopamine and is strongly implicated in human executive function. Numerous studies have reported associations of the COMT Val158Met (rs4680) polymorphism with executive function in healthy subjects. However, little work has investigated this in the Thai population and the relationship of age and education with this association remains unclear. Therefore, this study was designed to investigate the association of this polymorphism of the COMT gene with executive cognitive brain function in healthy subjects and the relationship with age and education. The Wisconsin Card Sorting Test (WCST) was performed to assess executive function in 254 healthy Thai subjects (aged 20-72 years). The results showed a significant association of rs4680 with executive function, in which Val/Met heterozygotes demonstrated better cognitive set shifting performance. Moreover, Met allele carriers showed a significantly stronger effect in the categories completed score than did Val homozygotes. Furthermore, age and education also showed a significant association with COMT genotype and WCST. These results revealed that executive cognitive function is associated with COMT genotype and influenced by age and/or education level in a Thai sample.

Atomoxetine selectively inhibits the reuptake of norepinephrine. Given the noradrenergic system's role in executive function, pharmacotherapy options that affect norepinephrine are of particular clinical interest in Parkinson disease-related executive dysfunction. The aim of this study was to assess the efficacy and safety of atomoxetine for Parkinson disease-related executive dysfunction. MEDLINE (1946 to May 2018) and EMBASE (1947 to May 2018) were queried using the search term combination: Parkinson's disease, Parkinson disease, inhibition, impulse behavior, impulse control disorder, executive function, executive dysfunction, cognition, cognitive dysfunction, cognitive defect, response inhibition, strategic planning, strategy, or verbal fluency and atomoxetine hydrochloride or atomoxetine. Studies analyzed for relevance evaluated clinical outcomes of patients treated with atomoxetine for Parkinson disease-related executive dysfunction. Studies appropriate to the objective were evaluated, including 1 open-label flexible dose trial, 2 placebo-controlled longitudinal trials, and 4 placebo-controlled crossover single-dose trials. In patients with Parkinson disease, treatment with atomoxetine resulted in improvements in several markers of executive dysfunction including impulsivity, risk taking, and global cognition. Study durations ranged from single-dose trials to 10 weeks and used varying doses of atomoxetine. Atomoxetine was well tolerated in most studies with some reports of gastrointestinal adverse effects and insomnia. Based on the reviewed literature, atomoxetine continues to be a therapy of interest for the treatment of executive dysfunction in patients with Parkinson disease. Larger long-term trials are necessary to further define the role of atomoxetine for patients with Parkinson disease-related executive dysfunction.

Readers Discuss: the Business of Nursing

Borderline Personality Disorder (BPD) features impulsivity, emotional dysregulation, and self-injurious behaviors (SIB). Cognitive deficits, such as executive dysfunction (ED) and working memory (WM) impairments, may drive these symptoms, yet their roles remain underexplored. This study examined relationships among ED, WM, impulsivity, and SIB in BPD to identify cognitive predictors of these behaviors. This cross-sectional study assessed 30 individuals with BPD per DSM-5 criteria. Participants completed the Barratt Impulsiveness Scale (BIS-11) for impulsivity, Deliberate Self-Harm Inventory (DSHI) for SIB, Wisconsin Card Sorting Test (WCST) for ED, and Letter-Number Sequencing (LNS) task for WM. Spearman's correlations and regression analyses evaluated associations between cognitive deficits, impulsivity, and SIB. Elevated impulsivity was linked to more WCST perseverative errors (ρ = 0.45, p = .02) and lower LNS scores (ρ = -0.38, p = .04). SIB correlated with ED (ρ = 0.41, p = .03) but not WM (ρ = -0.20, p > .05). High-impulsivity participants had greater WCST errors (median = 20 vs. 11, H = 8.12, p < .05) and lower LNS scores (median = 6 vs. 10, H = 7.33, p < .05) than low-impulsivity peers. Regression confirmed BIS-11 scores predicted WCST errors (β = 0.40, p < .01) and LNS performance (β = -0.35, p < .05). The ED and WM impairments were linked to impulsivity, with ED also tied to SIB. Cognitive remediation may reduce these behaviors. Lacking a control group, longitudinal research is needed.

To investigate attention, memory, verbal-linguistic ability, and executive functions in symptom-free young offspring having a parent with bipolar I disorder (BD1O) in comparison with healthy controls (CO). Materials and methods: Thirty symptom-free BD1O and 37 CO were recruited. The groups (both all participants and those &amp;amp;gt;=11 years of age) were well-matched for age, sex, IQ, and years of education. The neurocognitive battery included the Rey Auditory Verbal Learning and Memory Test, Controlled Word Association Test, Digit Span Test, Trail Making Test, Auditory Consonant Trigram Test, Wisconsin Card Sorting Test, Stroop Test, and Test of Variables of Attention. Results: The BD1O group demonstrated impairments in psychomotor speed, focused attention, verbal attention, phonemic verbal fluency, short-term memory, and learning functions and performed marginally worse in divided attention, information processing, and working memory. No group difference was found in sustained attention, executive functions, or alternating attention. Conclusion: Divided attention, information processing, and working memory seem to be important in evaluating the cognitive pathology before the onset of affective psychopathology.

Clonazepam (CNZ) is a drug used for insomnia treatment. Our objective was to search CNZ effects on executive functions (EF) in patients with chronic primary insomnia (CPI)-CNZ treated. Ninety participants were studied divided into three groups: a group of patients with CPI only (n = 30), a group of patients with CPI-CNZ treated (n = 30) and a healthy control drug-free subjects group (n = 30). EF were examined by means of E-Prime and by the Tower of London tests. Data of the EF were compared between groups, and correlation calculations between EF and CNZ dose were performed. Patients with CPI-CNZ treated showed more deleterious effects on EF (attention, inhibition, working memory, planning, cognitive flexibility, and monitoring) than patients with CPI only. Attention and cognitive flexibility correlated with CNZ dose. In conclusion, CNZ treatment was associated with deficits in some EF in patients with CPI-CNZ treated compared to CPI only and controls. We found a dose dependency between CNZ and some EF deficits.