QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients.

Background: This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients. Methods: A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume. Results: Higher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps ≤ 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps ≤ 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks. Discussion: Iron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in non-demented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients.

Psychosocial and executive functioning late effects in pediatric brain tumor survivors after proton radiation.

PURPOSE: Pediatric brain tumor survivors can experience detrimental effects from radiation treatment. This cross-sectional, large cohort study examined late psychosocial and executive functioning effects in pediatric patients treated ≥ 3 years after proton radiation therapy (PRT). METHODS: Parents of 101 pediatric brain tumor survivors completed the Behavior Assessment System for Children and the Behavior Rating Inventory of Executive Function. Standard scores were compared to published normative means, rates of impairment (T-score > 65) were calculated, and demographic and clinical characteristics were examined. RESULTS: Mean age at PRT was 8.12 years and mean interval from PRT to assessment was 6.05 years. Half were female (49.5%), 45.5% received craniospinal irradiation (CSI), and 58.4% were diagnosed with infratentorial tumors. All mean T-scores were within normal range. Mean T-scores were significantly elevated compared to the norm on the withdrawal, initiate, working memory, and plan/organize scales. Rates of impairment were notably high in working memory (24.8%), initiate (20.4%), withdrawal (18.1%), and plan/organize (17.0%). Greater withdrawal was significantly associated with CSI and also with chemotherapy and diagnosis of hearing loss. Mean T-scores were significantly lower than the norm on the hyperactivity, aggression, conduct problems, and inhibition scales. No significant problems were identified with social skills or depression. Interval since treatment was not correlated with any scale. CONCLUSION: Although psychosocial and executive functioning was within the normal range, on average, social withdrawal and metacognitive executive functioning (working memory, initiating, planning/organizing) were areas of concern. Targeted yearly screening and proactive executive skill and social interventions are needed for this population.

Neuropsychiatric Symptoms in Rhombencephalosynapsis: A Clinical Report.

Rhombencephalosynapsis (RES) is a hindbrain malformation characterized by a missing cerebellar vermis with apposition or fusion of the cerebellar hemispheres. The present clinical case report provides a comprehensive, longitudinal overview of cognitive and affective manifestations in a 22-year-old patient with RES. The patient shows clinical signs of emotional reactivity and dysregulation, impulsivity, and impairments in executive functioning since early childhood. These features fit the constellation of neuropsychiatric symptoms observed in patients with congenital and acquired abnormalities of the posterior vermis. It is proposed that patients with RES may show affective and cognitive difficulties which increase their vulnerability to psychological stress and risk of developing mental health issues.

Executive functioning profiles and mathematical and reading achievement in Grades 2, 6, and 10.

Using a person-centered approach, we aimed to identify different executive functioning profiles to assess heterogeneity across individuals within the same school grade through latent profile analysis. A sample of 150 Grade 2 (7-8 years old), 150 Grade 6 (11-12 years old), and 150 Grade 10 (15-16 years old) children and adolescents were assessed on 11 different executive tasks representative of the three main executive functioning subcomponents (i.e., inhibition, cognitive flexibility, and working memory), fluid intelligence, processing speed, problem-solving, and reading comprehension. Three different executive functioning profiles of different patterns of interactions based on inhibition, cognitive flexibility, and working memory within and between grades were identified. Moreover, these profiles were differentially related to reading comprehension and mathematical achievement. Second, as expected, we did not find these profiles to be associated with sociodemographic variables such as chronological age or sex. Still, fluid intelligence and processing speed were differentially related to the different profiles at each grade. We also found that the executive functioning profiles interacted with each cognitive skill (i.e., fluid intelligence and processing speed) in predicting reading comprehension and math achievement. These findings provide valuable insights for developing preventive and intervention strategies in education.

Leveraging bifactor modeling to test prospective direct and indirect effects of adolescent alcohol use and externalizing symptoms on the development of task-general executive functioning.

Adolescence is a period of substantial maturation in brain regions underlying Executive Functioning (EF). Adolescence is also associated with initiation and escalation of Alcohol Use (AU), and adolescent AU has been proposed to produce physiological and neurobiological events that derail healthy EF development. However, support has been mixed, which may be due to (1) failure to consider co-occurring externalizing symptoms (including other drug use) and poor social adaptation, and (2) heterogeneity and psychometric limitations in EF measures. We aimed to clarify the AU-EF association by: (1) distinguishing general externalizing symptoms from specific symptoms (AU, aggression, drug use) using bifactor modeling, (2) testing prospective associations between general externalizing symptoms and specific symptoms, and task-general EF, as indexed by a well-validated computational modeling framework (diffusion decision model), and (3) examining indirect pathways from externalizing symptoms to deficits in task-general EF through poor social adaptation. A high-risk longitudinal sample (N = 919) from the Michigan Longitudinal Study was assessed at four time-points spanning early adolescence (10-13 years) to young adulthood (22-25). Results suggested a critical role of social adaptation within peer and school contexts in promoting healthy EF. There was no evidence that specific, neurotoxic effects of alcohol or drug use derailed task-general EF development.

Neuropsychological Functioning Among Patients with OCD in Asian Countries: A Systematic Review.

Objective: This systematic review aimed to identify the effect of obsessive compulsive disorder (OCD) on cognitive processes, such as memory, executive functioning, and cognitive flexibility, among the adult populations of Asian countries. Methods: The systematic review progressed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It is comprised of articles sourced from Asian countries published from 2018 to 2022, and literature about deficits in memory, executive functioning, and cognitive flexibility in the OCD population was gathered from five electronic databases, including Google Scholar, PubMed, Research Gate, Science Direct, and Wiley Online Library. Full-text impact factor articles in the English language were considered in this study. Results: This study screened 44 articles; five were included based on the eligibility criteria for the present systematic review. Four articles found cognitive deficits in the domains of executive functioning, memory, and cognitive flexibility among patients with OCD, whereas results of one article showed normal cognitive performance of the patients. Demographic variables showed no significant differences between patients with OCD and healthy controls. Conclusion: This systematic review indicated deficits specifically in the cognitive functioning and flexibility of patients with OCD. Despite a noticeable prevalence of OCD in Asian countries, the literature on correlates and neurological functioning is scarce. Further studies are required to examine the effects on the larger population and provide knowledge in those countries and areas where people are suffering because of minimal knowledge regarding OCD.

Inhibitory P300 subprocesses and neural compensation in genetic risk for Alzheimer's disease: The case for temporal-spatial principal component analysis.

The P300 event-related potential (ERP) is widely investigated in cognitive neuroscience, including related to aging, with smaller amplitudes and delayed latency consistently reported in Alzheimer's disease (AD). Given that AD-related neurological changes begin years before symptom onset, ERPs in asymptomatic elders with AD risk may characterize early changes. ERPs are seldom studied in this population. Yet, healthy carriers of apolipoprotein-E (APOE) ε4 have evidenced delayed P300 latencies, while P300 amplitude differences are seldom found. However, despite its frequent study, the specific cognitive processes reflected by P300 remain unclear. We propose that these challenges are due to the relatively long P300 window, which likely encompasses multiple underlying subprocesses that overlap in time. Temporal-spatial principal component analysis (tsPCA) maintains the high temporal resolution of EEG and is better suited to isolate processes that overlap in time. Thus, we interrogated APOE ε4 differences in P300 activity during successful stop-signal inhibitory control in healthy, cognitively intact older adults (25 ε4-, 20 ε4+), using both conventional ERP metrics (i.e., mean and peak amplitude) and P300 tsPCA factors. P300 amplitudes did not differ by ε4 using conventional metrics. tsPCA revealed two P300 factors in each ε4 group: first, a Posterior P300 (attention allocation) factor, and second, a relatively Anterior P300 (performance monitoring, evaluating, and updating) factor. tsPCA uniquely revealed greater activity in ε4+ vs. ε4- in Anterior P300. ε4 groups had comparable task performance, suggesting that greater P300 activity in ε4+ likely reflects neural compensation for ε4-related deficits, thereby enabling the maintenance of good task performance.

Executive deficits after SARS-CoV-2 infection: A cross-sectional population study.

Importance: Despite the major implications of executive deficits in day-to-day functioning, few studies have investigated this in post-acute sequelae of SARS-CoV-2 infection using standardized measures that differentiate between aspects of executive function. Objective: Examine whether SARS-CoV-2 infection is associated with deficits in executive functions and if so, investigate the duration of this association. Design Setting and Participants: The present research has a cross-sectional design and uses data from the Norwegian Covid-19 Cohort study. The current cohort (n = 8102) completed the Behavior Rating Inventory of Executive Function- Adult Version (BRIEF-A) electronically between April 2021 and September 2021. During the assessment, 4183 of the included participants had a prior positive polymerase chain reaction test (PCR) for SARS-CoV-2 and 3919 were untested or had a confirmed negative PCR test. Exposure: Laboratory-confirmed SARS-CoV-2 infection. Main outcomes and measures: Executive functions were measured using the BRIEF-A, a self-report questionnaire comprising 75 items within nine theoretically and empirically distinct clinical scales. All participants self-reported on demographical variables and comorbidity. Information on sex and age was derived from the personal identification number, and vaccination status was obtained from the Norwegian Immunization Registry (SYSVAK). Results: Participants with a positive SARS-CoV-2 status reported executive deficits in everyday life above the clinical threshold (T-score ≥65) more often than non-infected controls (383 vs. 225). Specifically, the SARS-CoV-2 positive status group indicated significantly more deficits related to metacognition, with the greatest difference demonstrated for working memory. This difference remained when adjusting for various demographic factors and comorbidities, with significantly greater odds of reporting above the clinical threshold following SARS-CoV-2 infection, as observed on the global executive composite score 6-12 months after infection (OR 1.97; 95% CI 1.51 to 2.55). Conclusions: Our study confirms more perceived executive deficits following SARS-CoV-2 infection compared to non-infected controls, with metacognitive aspects being the most affected. These findings shed light on the potential functional difficulties that individuals may encounter during the post-acute phase of SARS-CoV-2 infection and may guide further development of targeted interventions addressing metacognitive domains of executive functioning.

Longitudinal associations of effort and reward at work with changes in cognitive function: evidence from a national study of U.S. workers.

PURPOSE: This study aimed to examine longitudinal associations of workplace effort and reward with changes in cognitive function among United States workers. METHODS: Data from the national, population-based Midlife in the United States (MIDUS) study with a 9-year follow-up were used. Validated workplace effort and reward scales were measured at baseline, and cognitive outcomes (including composite cognition, episodic memory, and executive functioning) were measured with the Brief Test of Adult Cognition by Telephone (BTACT) at baseline and follow-up. Multivariable linear regression analyses based on generalized estimating equations (GEE) examined the longitudinal associations under study. RESULTS: Among this worker sample of 1,399, after accounting for demographics, socioeconomics, lifestyle behaviors, health conditions, and job control, high reward at baseline was associated with increased composite cognition (regression coefficient: 0.118 [95% CI: 0.049, 0.187]), episodic memory (0.106 [0.024, 0.188]), and executive functioning (0.123 [0.055, 0.191]) during follow-up. The joint exposure of 'high effort and high reward' was also associated with increased composite cognition (0.130 [0.030, 0.231]), episodic memory (0.131 [0.012, 0.250]), and executive functioning (0.117 [0.017, 0.216]), while the combination of 'low effort and high reward' was associated with increased composite cognition (0.106 [0.009, 0.204]) and executive functioning (0.139 [0.042, 0.235]). CONCLUSION: Findings suggest that workplace high reward is related to improved cognitive scores among United States workers. Future research should investigate larger cohorts over longer timespans and expand into disease outcomes such as dementia. If these findings emerge as causal, relevant workplace rewards to promote worker cognitive health should be considered.

Identifying exercise and cognitive intervention parameters to optimize executive function in older adults with mild cognitive impairment and dementia: a systematic review and meta-analyses of randomized controlled trials.

Physical exercise is recognized for its beneficial effects on brain health and executive function, particularly through the careful manipulation of key exercise parameters, including type, intensity, and duration. The aim of this systematic review and meta-analysis was to delineate the optimal types, intensities, and durations of exercise that improve cognitive functions in older adults with mild cognitive impairment (MCI) or dementia. A comprehensive search was conducted in Scopus, Web of Science, and PubMed from their inception until December 2023. The methodological quality and publication bias of the included studies were assessed using the PEDro scale and Egger's regression test, respectively. Separate meta-analyses were performed to assess the overall impact of exercise on cognitive assessments and to explore the effects of different exercise types (i.e., aerobic, resistance, dual-task, mind-body, and multi-component exercises) and intensities (i.e., low, moderate, and high) on executive function. Results were presented as standardized mean differences (SMD) and 95% confidence intervals (95% CI). A meta-regression analysis was conducted to examine the correlation between exercise duration and mean effects. In total, 15,087 articles were retrieved from three databases, of which 35 studies were included in our final analyses. The results indicated high overall methodological quality (PEDro score = 8) but a potential for publication bias (t = 2.08, p = 0.045). Meta-analyses revealed that all types of exercise (SMD = 0.691, CI [0.498 to 0.885], p < 0.001) and intensities (SMD = 0.694, CI [0.485 to 0.903], p < 0.001) show significant effects favoring exercise. Notably, dual-task exercises (SMD = 1.136, CI [0.236 to 2.035], p < 0.001) and moderate-intensity exercises (SMD = 0.876, CI [0.533 to 1.219], p < 0.001) exhibited the greatest effect. No significant correlation was observed between exercise duration and SMD (R² = 0.038, p = 0.313). Overall, our meta-analyses support the role of physical exercise in enhancing executive function in older adults with MCI or dementia. It is essential to carefully tailor exercise parameters, particularly type and intensity, to meet the specific needs of older adults with MCI or dementia. Such customization is crucial for optimizing executive function outcomes and improving overall brain health.