Impaired Executive Function Research Articles

Response inhibition as a critical executive function in differentiating attention-deficit/hyperactivity disorder from autism spectrum disorder: a comprehensive attention test study

BackgroundAutism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are both associated with impairment in executive function, particularly in complex attention. Although previous studies using clinical assessments have attempted to delineate differences between these disorders, the findings have been inconclusive. Our study aims to elucidate the differences of endophenotype between ASD, ADHD, and their co-occurring condition utilizing a uniform computerized test.MethodsThe study included children diagnosed with ASD, ASD co-occurring with ADHD (ASD+ADHD), or ADHD who completed the comprehensive attention test (CAT) at Severance Hospital between October 2013 to May 2023. We excluded children with intellectual disability and comorbid major psychiatric or neurologic disorders possibly affecting attention measurement. The participants were categorized into three groups for the comparative analysis of CAT measures: (a) ASD (n=112), (b) ASD+ADHD (n=155), and (c) ADHD (n=104). The study also conducted an exploratory analysis utilizing multivariate linear regression analysis to examine the association between the CAT measures and parent-reported scales.ResultsNotably, the ASD+ADHD and ADHD groups exhibited higher frequency of commission errors (CE) and perseveration errors (PE) compared to the ASD group. In the exploratory analysis, a significant negative association was observed between reaction time (RT) and both the social communication questionnaire (SCQ) and the child behavior checklist (CBCL) externalization scores in the ASD+ADHD and ADHD groups. The ASD+ADHD group tended to show higher standard deviation of reaction time (RTSD) compared to the ASD group.ConclusionsOur findings suggest that impaired response inhibition is more pronounced in ADHD compared to ASD. We propose altered visual attention, reflecting response inhibition, may serve as potential endophenotypic markers differentiating ADHD from ASD in attentional assessment. Elevated RTSD in the ASD+ADHD group demonstrates additive pathology, suggesting that the neurological mechanisms underpinning impaired sustained attention may differ between the two conditions.

Manifestation of Psychosis and Impairments of Executive Functions Emphasize the Interaction of Psychological and Neurological Dysfunctions in People Who Use Methamphetamine

Aim: Cumulative evidence has demonstrated the neurotoxic effect of methamphetamine (Meth) on the central nervous system. Meth can induce psychotic symptoms and impairments of cognitive abilities, including executive function (EF). Method: In this study, we hypothesized the interaction of the neurotoxic effects of Meth on psychotic symptoms and EF performances. The Stroop test evaluated the EF performances, Go/No-Go task, one-back test (OBT), and Wisconsin Card Sorting Test (WCST) in people who use Meth with psychosis (MWP) and without psychosis (MWOP) compared with healthy control participants. Result: The results showed that MWOP and MWP exhibited EF deficits in attention, working memory, and initial conceptualization. Moreover, a deficit in inhibition was observed in MWOP, while poorer processing speed and cognitive flexibility were found in MWP. Conclusion: The correlation between psychotic symptoms and poor EF performances was observed in MWP. These findings underline the interaction of the mechanistic neurotoxic effect of Meth to induce psychological and neurological dysfunctions in people who use Meth.

Orexinergic modulation of chronic jet lag-induced deficits in mouse cognitive flexibility.

Cognitive flexibility and working memory are important executive functions mediated by the prefrontal cortex and can be impaired by circadian rhythm disturbances such as chronic jet lag (CJL) or shift work. In the present study, we used mice to investigate whether (1) simulated CJL impairs cognitive flexibility, (2) the orexin system is involved in such impairment, and (3) nasal administration of orexin A is able to reverse CJL-induced deficits in cognitive flexibility and working memory. Mice were exposed to either standard light-dark conditions or simulated CJL consisting of series of advance time shifts. Experiment (1) investigated the effects of a mild CJL protocol on cognitive flexibility using the attentional set shifting task. Experiment (2) used a stronger CJL protocol and examined CJL effects on the orexin system utilizing c-Fos and orexin immunohistochemistry. Experiment (3) tested whether nasal orexin application can rescue CJL-induced deficits in cognitive flexibility and working memory, the latter by measuring spontaneous alternation in the Y-maze. The present data show that CJL (1) impairs cognitive flexibility and (2) reduces the activity of orexin neurons in the lateral hypothalamus. (3) Nasal administration of orexin A rescued CJL-induced deficits in working memory and cognitive flexibility. These findings suggest that executive function impairments by circadian rhythm disturbances such as CJL are caused by dysregulation of orexinergic input to the prefrontal cortex. Compensation of decreased orexinergic input by nasal administration of orexin A could be a potential therapy for CJL- or shift work-induced human deficits in executive functions.

Cortical Alterations Associated with Executive Function Deficits in Youth with a Congenital Heart Defect

Abstract Adolescents and young adults born with a complex congenital heart defect (CHD) are at risk for executive function (ExF) impairments, which contribute to the psychological and everyday burden of CHD. Cortical dysmaturation has been well described in fetuses and neonates with CHD and early evidence suggests that cortical alterations in thickness, surface area, and gyrification index are non-transient and can be observed in adolescents with CHD. However, cortical alterations have yet to be correlated with ExF deficits in youth with CHD. This study aims to use a data-driven approach to identify the most important cortical features associated with ExF deficits in adolescents and young adults with CHD. To do so, we combined two comparable datasets acquired at the Research Institute of the McGill University Health Centre and the University Children’s Hospital Zurich each including both youth with CHD and healthy controls. For each participant, a high-resolution T1-weighted magnetic resonance image, a self-reported ExF assessment (the Behaviour Rating Inventory of Executive Function— Adult Scale), and their clinical and demographic characteristics were available. Corticometric Iterative Vertex-Based Estimation of Thickness (CIVET) was used to extract cortical thickness, cortical surface area, and local gyrification index measures. Using orthogonal projective non-negative matrix factorization (OPNMF), we identified non-overlapping spatial components that integrate cortical thickness, cortical surface area, and local gyrification index and capture structural covariance across these features. Behavioural partial least squares correlation (bPLS) analysis was then used to compute correlations between the individual variability in the OPNMF covariance patterns and ExF outcomes for each subject. A total of 56 youth with CHD who underwent cardiopulmonary bypass surgery before three years of age and 56 age- and sex-matched healthy controls were included in our analyses. Cortical grey matter volume, cortical thickness, and cortical surface area were found to be significantly reduced in CHD patients compared to controls. OPNMF identified 12 stable cortex-wide components summarizing the inter-subject variability in cortical thickness, cortical surface area, and local gyrification index. bPLS revealed two significant latent variables (LV) accounting for a total of 82.8% of the variance in the sample, each describing distinct patterns between the brain and cognitive data. LV1 summarized a pattern of belonging to the CHD group, worse scores on most BRIEF-A scales, younger age at MRI, and female sex. This pattern was associated with increased cortical thickness, local gyrification index, and decreased cortical surface area in several OPNMF components. Finally, we identified a positive relationship between the LV1 brain-behaviour pattern and total aortic cross-clamp time in the CHD group, indicating that longer aortic cross-clamp time was associated with worse neurodevelopmental outcomes. In this study, we uncover novel multivariate relationships between ExF and alterations in cortical thickness, surface area, and local gyrification index in adolescents and young adults with CHD using a data-driven approach. Although our findings highlight the important role played by the cortex in higher order cognitive processes, future studies are needed to elucidate the individual contribution of individual and clinical attributes into the deficits observed in this population.

Self-confidence as a mediator in the relationship between executive functioning and depression among ICU survivors: a latent variable analysis

BackgroundExecutive dysfunction and depression are common among ICU survivors, yet the mechanisms linking these two factors remain poorly understood. Self-confidence has been implicated as a key mediator in the relationship between cognitive impairments and mental health outcomes. This study aimed to explore the mediating role of self-confidence in the association between executive functioning and depression in ICU survivors.MethodA provisional questionnaire was used in a cross-sectional study to assess quality of life in 395 adult ICU survivors, each with a minimum 72-h stay at one of three ICUs at a Swedish university hospital, six months to three years post-discharge. Responses to questions on executive function, self-confidence, and depression were analysed. Structural equation modelling and confirmatory factor analysis were employed to examine the mediating effect of self-confidence on the relationship between executive function and depression. Model fit was evaluated using established indicators. Reliability of the measures was assessed using McDonald’s Omega and Cronbach’s Alpha.ResultsA significant positive correlation was found between depressive symptoms and both diminished self-confidence (r = 0.80, p < 0.001) and poorer executive function (r = 0.55, p < 0.001). Additionally, a correlation was observed between reduced self-confidence and compromised executive function (r = 0.62, p < 0.001). Age was negatively associated with depression, self-confidence, and executive function, while male gender was positively correlated with higher self-confidence.Mediation analysis revealed that the effect of impaired executive function on depressive symptoms was fully mediated by diminished self-confidence (B = 0.45; 95% CI 0.34–0.59). The direct effect of executive function on depression became non-significant when self-confidence was included in the model (B = 0.07, p = 0.18), suggesting complete mediation. The overall model fit was satisfactory (CFI = 0.962; RMSEA = 0.075), highlighting the robustness of the mediation pathway.ConclusionsSelf-confidence mediates the relationship between executive function and depression among ICU survivors. Interventions aimed at enhancing self-confidence could mitigate depressive symptoms in the ICU survivor population. Longitudinal studies are needed to confirm these findings and further explore the causal pathways involved.Trial registration ClinicalTrials.gov Ref# NCT02767180; Registered 28 April 2016.

A novel approach to ADHD classification based on severity and emotional impairment: Findings from artificial intelligence analysis

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder characterized by symptoms of inattention and executive dysfunction, although there is not always agreement on the onset, course and long-term stability of the diagnosis. This study aims to detect differences in the cognitive profile according to the subtype of ADHD following a professional diagnosis and to propose an alternative classification. The scores obtained for each cognitive construct were compared using the Student’s t-test. In order to explore different diagnostic categories based on groupings made by Artificial Intelligence (AI) subjects were grouped based on their performance through the K-means clustering technique. The results obtained by Artificial Intelligence (AI) identified groups based on the severity of the cognitive profile and the presence of emotional impairment. Difficulties in perceived planning within family and school environments were highlighted as major risk factors in the severity of ADHD in children. Emotional disturbances perceived by both parents, such as depressive symptoms, anxiety, and somatization, were observed subsequently. In accordance with the results, an alternative way to classify ADHD is possible, involving categorization according to the presence or absence of emotional impairment, along with the severity of impairment in attentional and executive functions.

Executive functioning in adults with attention deficit hyperactivity disorder: A systematic review

Introduction: Executive function deficits are associated with attention deficit hyperactivity disorder (ADHD) in both children and adults. The inattentive subtype is primary related to “cold” executive functions, while the hyperactive subtype is related to “warm” executive functions. Objective: To systematically review studies on executive functioning in adults with attention deficit hyperactivity disorder published during the last decade. Methodology: A documentary research was conducted, encompassing 33 articles retrieved from PubMed, Web of Science and EBSCO platforms. The analysis considered years and countries of publication, attention deficit hyperactivity disorder diagnostic criteria, participants, comorbidities, subtypes, medication use, assessment tools, and processes of executive functions evaluated. Results: It was evidenced that there is a high percentage of adults with attention deficit hyperactivity disorder who present a deficit or lower performance in executive function tests. However, the results varied depending on specific characteristics of the study and/or participants, which confirms the heterogeneity of the disorder. In addition, the main instruments for measuring executive functions and diagnostic criteria for adult attention deficit hyperactivity disorder were identified. Discussion: These results support the established links between attention deficit hyperactivity disorder , impaired executive functions, and major life activities found in the adult attention deficit hyperactivity disorder literature. However, some of the limitations were the poorly controlled variables such as comorbidities, attention deficit hyperactivity disorder subtypes that were not assessed, and usage of instruments that measure executive functions that can lead to reduced credibility of the results presented here. Conclusions: According to the results presented, there is a high percentage of adults with attention deficit hyperactivity disorder who present a deficit or lower performance in executive function tests, compared to both neurotypical adults and those with other psychiatric disorders. Further research is recommended to continue studies on the topic and to include other variables.

Association between trace elements and cognitive function among hemodialysis patients in Turkey.

Cognitive impairment is common among patients with hemodialysis. Hemodialysis patients have theoretical risks for both deficiency and accumulation of trace elements. We aimed to investigate the relationship between cognitive dysfunction and whole blood levels of trace elements in hemodialysis patients. We also aimed to examine the effect of baseline trace element status and cognitive dysfunction on mortality. Maintenance hemodialysis patients and age-and sex-matched controls were included. The whole blood levels of trace elements were measured by inductively coupled plasma mass spectrometry. Cognitive impairment was defined as a score of ≤24 points on the Montreal Cognitive Assessment test. Executive dysfunction was also defined as Trails A score of more than 75 s and Trails B score of more than 180 s. Forty-two patients and 35 controls were included. Cognitive impairment was detected in 69% of the patients and 45.7% of the controls (p = 0.039). Cognitively impaired patients had lower education years (p = 0.003) and higher whole blood levels of manganese (Mn) and lead (Pb) (p = 0.026, p = 0.019, respectively) compared to patients without cognitive impairment. Mn levels were also found statistically higher in patients with executive dysfunction compared to patients without executive dysfunction (p = 0.005). Lower education years and higher Pb levels were independent risk factors for cognitive impairment in hemodialysis patients (odds ratio [OR] 0.589 [95% confidence interval, CI 0.400-0.866, p = 0.007] and OR 1.047 [95% CI 1.001-1.096, p = 0.047, respectively]). Cognitive impairment, especially impaired executive function, is common among patients with hemodialysis patients. Cognitive impairment is not found to be associated in cross-sectional analysis with several modifiable end-stage renal disease- and dialysis-associated factors. The accumulation of trace elements especially Mn and Pb might exacerbate the cognitive dysfunction in hemodialysis patients.

Clinical features of vascular cognitive impairment

Vascular cognitive impairment (VCI) can occur in cerebrovascular disease of varying degree of severity, which requires further investigation.Objective: to identify specific features of attention deficit and executive function (EF) impairment in VCI and to determine the relationship between cognitive, neurological and radiological signs of the disease.Material and methods. The study involved 80 patients (51 with VCI – the main group and 29 healthy volunteers – the control group). All participants underwent clinical and neuropsychological examination and MRI of the brain. VCI was diagnosed according to 2014 VASCOG criteria. The neuropsychological examination included an assessment of the general cognitive function (MoCA test, MMSE); general EF (FAB, EXIT-25); episodic memory (12-word memory test and Benton Visual Retention Test); semantic memory (categorical association method); initiation and productivity of cognitive activity (literal associations); attention [TMT-A, Symbol-Digit Modalities Test (SDMT)]; cognitive flexibility (TMT-B); cognitive control (Stroop test).Results. As a result of the study, three subgroups of patients with VCI were identified: 1) predominantly attention deficit (AD); 2) AD and significant decrease in cognitive flexibility (CFD); 3) AD in combination with a significant cognitive control deficiency (CCD). The TMT-A and SDMT tests were significantly worse in all subgroups of VCI compared to the control group, with the worst SDMT score in subgroup 2. Subgroup 2 also had the longest time to complete the TMT-B test. Subgroup 3 was characterized by the worst Stroop test results, and uncontrolled arterial hypertension was more common in this group. Gait disturbances were significantly more frequent in subgroup 2, and increased reflexes of oral automatism and grasp reflex were observed in subgroup 3. White matter hyperintensity (WMH) was more pronounced in subgroup 2, and lacunar infarcts (LI) were more frequent in subgroup 3. Prevalence of LI and severity of WMH were lowest in subgroup 1.Conclusion. The main features of VCI are attention deficit and EF impairment, characteristics of EF disorders depend on the severity and type of vascular lesions of the brain. Progression of WMH is associated with more pronounced CFD and an increase in the number of LI is associated with CCD. There is a correlation between CFD and gait disturbances and between CCD and lack of primitive reflexes inhibition.

Genetically stratified Parkinson's disease with freezing of gait is related to specific pattern of cognitive impairment and non-motor dominant endophenotype.

Freezing of gait (FOG) is an important milestone in the individual disease trajectory of people with Parkinson's disease (PD). Based on the cognitive model of FOG etiology, the mechanism behind FOG implies higher executive dysfunction in PDFOG+. To test this model, we investigated the FOG-related phenotype and cognitive subdomains in idiopathic PD (iPD) patients without genetic variants linked to PD from the Luxembourg Parkinson's study. A cross-sectional analysis comparing iPDFOG+ (n = 118) and iPDFOG- (n = 378) individuals was performed, followed by the application of logistic regression models. Consequently, regression models were fitted for a subset of iPDFOG+ (n = 35) vs. iPDFOG- (n = 126), utilizing a detailed neuropsychological battery to assess the association between FOG and cognitive subdomains. Both regression models were adjusted for sociodemographic confounders and disease severity. iPDFOG+ individuals presented with more motor complications (MDS-UPDRS IV) compared to iPDFOG- individuals. Moreover, iPDFOG+ individuals exhibited a higher non-motor burden, including a higher frequency of hallucinations, higher MDS-UPDRS I scores, and more pronounced autonomic dysfunction as measured by the SCOPA-AUT. In addition, iPDFOG+ individuals showed lower sleep quality along with lower quality of life (measured by PDSS and PDQ-39, respectively). The cognitive subdomain analysis in iPDFOG+ vs. iPDFOG- indicated lower scores in Benton's Judgment of Line Orientation test and CERAD word recognition, reflecting higher impairment in visuospatial, executive function, and memory encoding. We determined a significant association between FOG and a clinical endophenotype of PD with higher non-motor burden. While our results supported the cognitive model of FOG, our findings point to a more widespread cortical impairment across cognitive subdomains beyond the executive domain in PDFOG+ with additional higher impairment in visuospatial function and memory encoding.

Postoperative Electroacupuncture Boosts Cognitive Function Recovery after Laparotomy in Mice.

Postoperative cognitive dysfunction (POCD) is a common complication that affects memory, executive function, and processing speed postoperatively. The pathogenesis of POCD is linked to excessive neuroinflammation and pre-existing Alzheimer's disease (AD) pathology. Previous studies have shown that acupuncture improves cognition in the early phase of POCD. However, POCD can last for longer periods (up to weeks and years). The long-term effects of acupuncture are unknown. In this study, we hypothesized that electroacupuncture (EA) could reduce inflammation and cognitive dysfunction induced by laparotomy over a longer period. We characterized the effects of postoperative EA on cognitive changes and investigated the underlying molecular mechanisms in mice. Laparotomy was performed in 3-month-old mice followed by daily EA treatment for 2 weeks. Our data indicated that laparotomy induced prolonged impairment in memory and executive functions, which were mitigated by postoperative EA. EA also reduced tau phosphorylation and suppressed the activation of tau-related kinases and glia, with effects comparable to ibuprofen. These findings demonstrate the beneficial effects of EA in a mouse model of POCD, suggesting that EA's ability to suppress neuroinflammation may contribute to its protective effects. In conclusion, EA may be a viable non-pharmacological intervention for managing POCD in different phases of the medical condition.

Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection.

Neuropsychiatric complications of SARS-CoV-2 infection, also known as neurologic postacute sequelae of SARS-CoV-2 infection (NeuroPASC), affect 10%-60% of infected individuals. There is growing evidence that NeuroPASC is a multi system immune dysregulation disease affecting the brain. The behavioral manifestations of NeuroPASC, such as impaired processing speed, executive function, memory retrieval, and sustained attention, suggest widespread WM involvement. Although previous work has documented WM damage following acute SARS-CoV-2 infection, its involvement in NeuroPASC is less clear. We hypothesized that macrostructural and microstructural WM differences in NeuroPASC participants would accompany cognitive and immune system differences. In a cross-sectional study, we screened a total of 159 potential participants and enrolled 72 participants, with 41 asymptomatic controls (NoCOVID) and 31 NeuroPASC participants matched for age, sex, and education. Exclusion criteria included neurologic disorders unrelated to SARS-CoV-2 infection. Assessments included clinical symptom questionnaires, psychometric tests, brain MRI measures, and peripheral cytokine levels. Statistical modeling included separate multivariable regression analyses of GM/WM/CSF volume, WM microstructure, cognitive, and cytokine concentration between-group differences. NeuroPASC participants had larger cerebral WM volume than NoCOVID controls (β = 0.229; 95% CI: 0.017-0.441; t = 2.16; P = .035). The most pronounced effects were in the prefrontal and anterior temporal WM. NeuroPASC participants also exhibited higher WM mean kurtosis, consistent with ongoing neuroinflammation. NeuroPASC participants had more self-reported symptoms, including headache, and lower performance on measures of attention, concentration, verbal learning, and processing speed. A multivariate profile analysis of the cytokine panel showed different group cytokine profiles (Wald-type-statistic = 44.6, P = .046), with interferon (IFN)-λ1 and IFN-λ2/3 levels higher in the NeuroPASC group. NeuroPASC participants reported symptoms of lower concentration, higher fatigue, and impaired cognition compatible with WM syndrome. Psychometric testing confirmed these findings. NeuroPASC participants exhibited larger cerebral WM volume and higher WM mean kurtosis than NoCOVID controls. These findings suggest that immune dysregulation could influence WM properties to produce WM volume increases and consequent cognitive effects and headaches. Further work will be needed to establish mechanistic links among these variables.

Abnormal changes in neuropsychological function, brain structure and cerebral perfusion in patients with unruptured intracranial aneurysms.

Patients with unruptured intracranial aneurysms (UIAs) often experience emotional changes and cognitive impairments. However, the specific mechanisms underlying these impairments are still not fully understood. In the present study, voxel-based morphometry (VBM) and surface-based morphometry (SBM) were employed to investigate structural alterations in 49 patients diagnosed with UIAs compared with 50 healthy controls. Additionally, this study aimed to analyze the correlations among cortical morphological indices, cerebral blood perfusion values and neuropsychological test results. Compared with control group, UIA patients exhibited increased gray matter volume in the right anterior orbitofrontal cortex and decreased gray matter volume in the left thalamus pulvinar and hippocampus. Furthermore, the fractal dimension was lower in the right postcentral gyrus and entorhinal cortex. The cerebral perfusion values in the abnormal brain regions demonstrated a downward trend, which was associated with a reduction in gray matter volume in the left thalamus pulvinar and hippocampus, elevated anxiety levels and impaired executive function. UIA patients are prone to cognitive impairment and emotional dysregulation, which are accompanied by subtle changes in local gray matter volume and decreases in fractal dimension and cerebral blood flow. These findings provide new insights into the potential mechanisms underlying the cognitive impairment observed in UIA patients.

Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats.

Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking. Adult male rats were trained to perform a "simple" or "complex" version of a delayed-match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression. Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence. These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance before drug exposure may predict vulnerability to future drug use.

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown. We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean. Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}]=0.44 [0.26, 0.76], p=0.003) and executive function (adjusted HR [95% CI]=0.60 [0.37, 0.97], p=0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory. CHIP was associated with lower risks of impairment in attention and executive function among CKD patients. Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

The cumulative impact of clinical risk on brain networks and associations with executive function impairments in adolescents with congenital heart disease.

Patients with congenital heart disease (CHD) demonstrate altered structural brain network connectivity. However, there is large variability between reported results and little information is available to identify those patients at highest risk for brain alterations. Thus, we aimed to investigate if network connectivity measures were associated with the individual patient's cumulative load of clinical risk factors and with family-environmental factors in a cohort of adolescents with CHD. Further, we investigated associations with executive function impairments. In 53 adolescents with CHD who underwent open-heart surgery during infancy, and 75 healthy controls, diffusion magnetic resonance imaging and neuropsychological assessment was conducted at a mean age of 13.2 ± 1.3 years. Structural connectomes were constructed using constrained spherical deconvolution tractography. Graph theory and network-based statistics were applied to investigate network connectivity measures. A cumulative clinical risk (CCR) score was built by summing up binary risk factors (neonatal, cardiac, neurologic) based on clinically relevant thresholds. The role of family-environmental factors (parental education, parental mental health, and family function) was investigated. An age-adjusted executive function summary score was built from nine neuropsychological tests. While network integration and segregation were preserved in adolescents with CHD, they showed lower edge strength in a dense subnetwork. A higher CCR score was associated with lower network segregation, edge strength, and executive function performance. Edge strength was particularly reduced in a subnetwork including inter-frontal and fronto-parietal-thalamic connections. There was no association with family-environmental factors. Poorer executive functioning was associated with lower network integration and segregation. We demonstrated evidence for alterations of network connectivity strength in adolescents with CHD - particularly in those patients who face a cumulative exposure to multiple clinical risk factors over time. Quantifying the cumulative load of risk early in life may help to better predict trajectories of brain development in order to identify and support the most vulnerable patients as early as possible.

NEUROCOGNITIVE EVALUATION OF PATIENTS WITH DIGEORGE SYNDROME

BackgroundDiGeorge syndrome (DGS), the most common microdeletion syndrome, affects multiple organs, including the heart, the nervous system, and the immune system. In this study, we aimed to evaluate the clinical, laboratory, brain MRI, and neurocognitive findings of our patients with DGS. MethodsClinical and laboratory data of fifty-two patients with DGS between June 2000- March 2022 were evaluated retrospectively. Brain MRI and neuropsychological tests were performed to assess the neurocognitive status of the patients. ResultsFifty-two patients (28 males and 24 females) were included in our study. Fifteen of them died during the follow-up. All 37 patients who are alive had partial DGS. The median age of patients was ten years and seven months, and the median age at diagnosis was five years and four months. Bilateral conduction deceleration in the anterior visual pathways in 6 (20%) of 30 patients was determined by the VEP (Visual Evoked Potentials). The auditory brainstem evoked potential test (BAEP) showed sensorineural hearing loss in 11 out of 30 (36.6%) patients. Brain MRI disclosed brain parenchymal abnormalities in 18 out of 25 (72%) patients. Impairments in executive functions, expressive language, and verbal memory were noted in 18 patients who were neuropsychologically assessed. ConclusionIt is important to keep in mind that patients with DiGeorge syndrome may be accompanied by neurocognitive findings. Awareness of the potential for underlying psychiatric and neurodevelopment disorders is key to anticipatory guidance, optimization of therapies, and maximizing life quality.

Parents' Distress and Demands for Children With Cancer-Related Cognitive Impairment in Western China: A Qualitative Study.

Cancer-related cognitive impairment is one of the common complications in children with cancer, but our understanding of their experience with cognitive deficits remains limited. From the perspective of parents, this study aimed to explore the distress and demands faced by children with cancer-related cognitive impairment, to provide references for developing targeted intervention strategies for cancer children. We used a purposeful sampling method to conduct semi-structured interviews with the parents of 18 children with cancer-related cognitive impairment. The transcripts were analyzed using Colaizzi's method. Three categories and 11 subcategories were obtained from the data analysis, including diverse levels of cognitive impairment in children (speech communication difficulties, impaired executive function, attention deficit, and intellectual disability), persistent negative emotions (anxiety and worry, complaints and resentment, negative avoidance and positive experiences after psychological adjustment), multiple needs (need for disease information, need for professional management, and an urgent need for more external support). Parents of children with cancer-related cognitive impairment face a significant psychological burden, coupled with confusion and numerous inquiries regarding the symptoms and management of their children's cognitive impairment. It is imperative for medical professionals to strengthen the dissemination of information related to cancer-associated cognitive impairments, while promptly recognizing and intervening in related symptoms. Rational allocation of resources, establishment of targeted support systems, and enhancement of social acceptance may be the key points that policymakers could consider. These efforts hold immense significance, as they play a pivotal role in elevating cognitive capabilities and enhancing the overall quality of life for children with cancer.

Structural and functional brain markers of cognitive impairment in healthcare workers following mild SARS-CoV-2 infection during the original stream.

Severe acute respiratory syndrome coronavirus 2 infection often involves the nervous system, leading to cognitive dysfunctions, fatigue and many other neurological signs that are becoming increasingly recognized. Despite mild forms of the disease accounting for most cases worldwide, research on the pathophysiology driving mild coronavirus disease 2019 (COVID-19) has received little attention. In this respect, recent evidence has pointed out that around 30-40% of non-critical, mild-to-moderate severity COVID-19 survivors may display cognitive disturbances several months post-illness. Hence, the impact of COVID-19 on the brain structure and function, through potential neuropathological mechanisms underpinning cognitive alterations in post-mild COVID-19 infections, remains largely unexplored. This retrospective multicentre observational cohort study, entirely based on a healthcare worker sample (n = 65; 55% females, aged 21-61), investigated the cognitive status and the structural and functional brain integrity among non-hospitalized individuals who developed mild COVID-19 symptoms during the occurrence of severe acute respiratory syndrome coronavirus 2 variants Alpha to Delta, compared with healthy controls tested before the pandemic onset. All evaluations were performed at an average of 9-month follow-up post-infection period. Participants completed a comprehensive neuropsychological assessment and structural and functional MRI exams. Radiological inspection sought to detect the presence of white matter hyperintensities on axial fluid-attenuated inversion recovery images. Global and regional grey matter integrity assessment, analysing changes in grey matter volumes and cortical thinning, and functional connectivity alterations of resting-state brain networks were also conducted. Regression analyses tested the relationships between the presence of specific cognitive impairments and potential structural and functional brain findings. Our results revealed that clinical, cognitive screening and neuropsychological examinations were average between both groups, except for specific impairments related to executive functions in the mild COVID-19. Compared to healthy controls, mild COVID-19 subjects exhibited increased juxtacortical white matter hyperintensities, thalamic and occipital volume loss and diminished resting-state functional connectivity involving the left precuneus and cuneus in default-mode network and affecting the right angular gyrus and left precuneus in the dorsal attentional network. Reduced thalamic volume was the only variable selected in the final model explaining the observed executive function impairment in mild COVID-19. The presence of cognitive, structural and functional brain abnormalities over time suggests that the action of widespread neurovascular and inflammatory phenomena on the nervous system might also occur in mild forms following COVID-19 infection rather than permanent brain damage linked to the direct or indirect action of the virus. Our findings emphasize the need to pay attention to the long-term brain-related consequences of mild COVID-19 infections during the original stream.

Retinal Microvasculature Changes Linked to Executive Function Impairment after COVID-19

Background/Objectives: Studies using optical coherence tomography angiography (OCTA) have revealed that individuals recovering from COVID-19 have a reduced retinal vascular density (VD) and larger foveal avascular zones (FAZs) than healthy individuals, with more severe cases showing greater reductions. We aimed to examine aspects of the retinal microvascularization in patients with post-COVID-19 condition (PCC) classified by COVID-19 severity and how these aspects relate to cognitive performance. Methods: This observational cross-sectional study included 104 PCC participants from the NAUTILUS Project, divided into severe (n = 59) and mild (n = 45) COVID-19 groups. Participants underwent cognitive assessments and OCTA to measure VD and perfusion density (PD) in the superficial capillary plexus (SVP) and FAZ. Analysis of covariance and partial Pearson and Spearman correlations were used to study intergroup differences and the relationships between cognitive and OCTA variables. Results: Severe PCC participants had significantly lower central (p = 0.03) and total (p = 0.03) VD, lower central (p = 0.02) PD measurements, and larger FAZ areas (p = 0.02) and perimeters (p = 0.02) than mild cases. Severe cases showed more cognitive impairment, particularly in speed processing (p = 0.003) and executive functions (p = 0.03). Lower central VD, lower central PD, and larger FAZ areas and perimeters were associated with worse executive function performance in the entire PCC sample and in the mild COVID-19 group. Conclusions: Retinal microvascular alterations, characterized by reduced VD and PD in the SVP and larger FAZ areas, were associated with cognitive impairments in PCC individuals. These findings suggest that severe COVID-19 leads to long-lasting microvascular damage, impacting retinal and cognitive health.