Impaired Executive Function Research Articles

Further investigations into performance variance on the Multiple Errands Test.

The Multiple Errands Test (MET) is a complex, performance-based assessment that is useful for characterising the impact of impairments of executive function on everyday activities. However, performance variance amongst those without neurological pathology, and the impact of non-cognitive factors on this, requires further investigation. This was a cross-sectional analytic study, conducted with a convenience sample of 40 neurologically intact community-dwelling Australian adults. Participants completed a hospital or shopping centre version of the MET, where their Performance Efficiency, Task Completions and Rule Breaks were recorded. Non-cognitive factors of interest were demographic (age, sex and education), psychological (measured with the Hospital Anxiety and Depression Scale and self-ratings of test anxiety) and assessment-related (assessment site, self-reported site familiarity and observed strategy use). MET performance was analysed using descriptive statistics. A series of standard multiple and binary logistic regression analyses examined the relationships between MET performance and non-cognitive factors. Most participants (n = 35, 87.5%) completed at least 10 of the 12 prescribed tasks and broke an average of four rules (SD = 2.36). They achieved an average performance efficiency rating of 0.75/1 (SD = 0.15), suggesting variability in the extent to which participants made non-essential location stops and/or failed to complete tasks whilst at an essential location. The assessment site and participant site familiarity had a statistically significant (p < 0.05) impact on Performance Efficiency and Task Completion scores, and psychological factors had a statistically significant (p < 0.05) relationship with Rule Breaks. Findings suggest that the impact of factors other than cognition should be considered when interpreting MET performance. The assessment site and participant site familiarity may contribute to significant variability in Performance Efficiency scores. Clinicians should also be aware of the potential impact of these assessment-related factors on Task Completions and psychological distress on Rule Breaks.

Impact of insulin resistance on mild cognitive impairment in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease

AimsInsulin resistance (IR) is a pivotal factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Nevertheless, the impact of IR on cognitive dysfunction in T2DM patients with NAFLD remains inadequately understood. We aim to investigate the effect of IR on mild cognitive impairment (MCI) in T2DM individuals with NAFLD.Materials and methods143 T2DM individuals were categorized into Non-MCI and MCI groups, as well as Non-NAFLD and NAFLD groups. Clinical parameters and cognitive preference test outcomes were compared. Correlation and regression analyses were executed to explore the interconnections between IR and cognitive details across all T2DM patients, as well as within the subgroup of individuals with NAFLD.ResultsIn comparison to the Non-MCI group, the MCI group displayed elevated HOMA-IR levels. Similarly, the NAFLD group exhibited higher HOMA-IR levels compared to the Non-NAFLD group. Additionally, a higher prevalence of MCI was observed in the NAFLD group as opposed to the Non-NAFLD group. Notably, HOMA-IR levels were correlated with Verbal Fluency Test (VFT) and Trail Making Test-B (TMTB) scores, both related to executive functions. Elevated HOMA-IR emerged as a risk factor for MCI in the all patients. Intriguingly, increased HOMA-IR not only correlated with TMTB scores but also demonstrated an influence on TMTA scores, reflecting information processing speed function in patients with NAFLD.ConclusionIR emerges as a contributory factor to cognitive dysfunction in T2DM patients. Furthermore, it appears to underlie impaired executive function and information processing speed function in T2DM individuals with NAFLD.

SARS-CoV-2 infection and cognition in community-dwelling and nursing home residents in southern Switzerland

BackgroundCOVID-19 patients can report ‘brain fog’ and may exhibit cognitive symptoms for months after recovery (Cognitive COVID). However, evidence on whether and the extent to which SARS-CoV-2 infection impacts cognition irrespective of COVID-19 course and severity is limited to clinical samples and mainly comes from prognostic studies. We aimed to explore the association between serologically confirmed SARS-CoV-2 infection and cognitive functioning in community-based and institutionalized older adults, irrespective of COVID-19 symptoms. MethodsWe conducted a case-control study nested into two cohorts in Southern Switzerland. Eligible subjects were Italian speaking older adults, without a previous diagnosis of dementia, who underwent serological testing for anti-SARS-CoV-2 antibodies between November 2020 and July 2021. We manually selected age-, sex- and education-matched cases (i.e., individuals with a serologically confirmed SARS-CoV-2 infection), with seronegative controls, and we conducted in-person neuropsychological assessments using validated, highly sensitive cognitive tests. ResultsWe completed 38 neuropsychological assessments in a mostly female sample of older adults (Mean age: 83.13 ± 8.95; 86.8% women). 17 were community dwelling individuals while 21 lived in a nursing home. As expected, socio-demographic characteristics of age, gender and educational level were similarly distributed between cases (n = 14) and controls (n = 24). In linear regression models, cases had significantly lower scores in cognitive tasks of memory (β = −0.367, p = 0.023), attention (β = 0.428, p = 0.008) and executive functions (β = 0.326, p = 0.046). We found no significant difference in tests of language and spatial-temporal orientation (all p values > 0.05). ConclusionsSARS-CoV-2 infection was associated with cognitive impairment in memory, attention, and executive functions in older adults. Our findings are consistent with mechanistic evidence of the neurotropism of the virus and provide empirical support for the “Cognitive COVID” construct also in non-clinical samples. With nearly 800 million COVID-19 cases (in April 2023), and many more infections worldwide, the clinical and public health implications of Cognitive COVID due to SARS-CoV-2 infection may be massive and warrant further epidemiological investigations.

Effects of mammary cancer and chemotherapy on neuroimmunological markers and memory function in a preclinical mouse model

Treatment modalities for breast cancer, including cyclophosphamide chemotherapy, have been associated with the development of cognitive decline (CRCD), which is characterized by impairments in memory, concentration, attention, and executive functions. We and others have identified a link between inflammation and decreased cognitive performance in patients with breast cancer receiving chemotherapy. In order to better understand the inflammation-associated molecular changes within the brain related to tumor alone or in combination with chemotherapy, we orthotopically implanted mouse mammary tumors (E0771) into female C57BL/6 mice and administered clinically relevant doses of cyclophosphamide and doxorubicin intravenously at weekly intervals for four weeks. We measured serum cytokines and markers of neuroinflammation at 48 h and up to one month post-treatment and tested memory using a reward-based delayed spatial alternation paradigm. We found that breast tumors and chemotherapy altered systemic inflammation and neuroinflammation. We further found that the presence of tumor and chemotherapy led to a decline in memory over time at the longest delay, when memory was the most taxed, compared to shorter delay times. These findings in a clinically relevant mouse model shed light on possible biomarkers for CRCD and add to the growing evidence that anti-inflammatory strategies have the potential to mitigate cancer- or treatment-related side effects.

Ayurvedic Management of Comorbid State of Autism with Attention Deficit Hyperactivity Disorder w.s.r Unmada

Unmada a term used in Ayurveda, refers to a condition characterized by mental instability, restlessness and abnormal behaviors. It similar to modern day autism spectrum disorder (ASD) and attention deficit hyperactive disorder (ADHD). ASD and ADHD are neuro developmental and neuropsychiatric disorder. These disorders have shared genetic heritability and are both associated with shared impairment in social functioning and executive functioning. However, in the phenotypic presentation of the impairment which characterized ASD and ADHD. The fundamental principles of Ayuvedic management are to restore the balance of the Doshas. In the case of Unmada, particularly when comorbid with autism and ADHD, the focus on pacifying the aggravated Vata dosha. This can be achieved through a combination of dietary modification, lifestyle changed, Balpanchkarma and Marma therapies and Medhya Dravya. Aim and Objective: A case study of Ayurvedic management of comorbid state of Autism and Attention Deficit Hyperactivity Disorder w.s.r Unmaad. Material and Method: A 5-year-old female patient was come to the OPD of Kaumarbhritya Department, Rishikul Campus, UAU, Haridwar. With complain of difficulty in speaking as per development age, poor eye contact, hyperactive in nature with addiction of mobile in the last three year. This condition can be understood as Unmada. Treatment including with some Balpanchkarma and Marma therapies, and Ayurvedic formulations for 2-3 months. Result: There significant improvement in the condition of the patient. Ayurvedic intervention in this case reveals the true potential and efficacy of our Ayurvedic science.

Occupational therapy practice to support executive function impairment after acquired brain injury: A UK clinical survey

Introduction: This study explored treatment of executive functioning impairment in adults after acquired brain injury (ABI), clinician’s confidence and support received, in a sample of occupational therapists in the United Kingdom. Methods: A 24-item online questionnaire was sent to 750 members of the Royal College of Occupational Therapists Specialist-Section in Neurological Practice. Data was collected at a nominal and ordinal level and included yes/no Likert-type scale and free field comments. Descriptive statistical analysis was completed. Results: Seventy-six occupational therapists working in a range of neurological settings completed the survey. Frequently used interventions included education ( n = 57, 75%), task modification ( n = 56, 73%), instrumental activities of daily living (ADL) ( n = 54, 71%), personal ADL ( n = 53, 70%) and goal setting ( n = 53, 70%). Seventy-one percent used metacognitive strategies. Occupation-based metacognitive approaches were rarely used. Thirty-one (41%) participants reported being fairly confident and 28 (37%) were very confident. Support for clinical practice was accessed most frequently through joint clinical sessions ( n = 30, 39%). Findings: Participants used various clinical interventions to treat service users with executive dysfunction after ABI. Meta-cognitive strategies were employed; however, occupation-based metacognitive approaches were infrequently utilised, suggesting uncertainty in adopting these in practice. The need for further training on evidence-based interventions and knowledge translation support was highlighted.

Childhood trauma, intraindividual reaction time variability, baseline respiratory sinus arrhythmia, and perceived relapse tendency among males with substance use disorders

ABSTRACTBackground: People with substance use disorders (SUDs) who have experienced serious childhood trauma may have executive function impairments contributing to relapse. Baseline respiratory sinus arrhythmia (RSA) reflects physiological regulation capacity, which has been found to buffer the negative effects of childhood trauma. Baseline RSA has also been found to be related to intraindividual reaction time variability (IIRTV), which is an index of executive function.Objectives: The present study examined the relationship between childhood trauma and perceived relapse tendency, the mediation role of IIRTV, and the moderation role of baseline RSA.Methods: The study is cross-sectional, a total of 110 males with SUDs participated (Mage = 46.45 years, SD = 11.24). The Childhood Trauma Questionnaire and Intention to Rehabilitate Questionnaire were used to assess childhood trauma and perceived relapse tendency, the two-choice oddball task was used to measure IIRTV, and electrocardiogram (ECG) data were collected to obtain baseline RSA.Results: IIRTV mediated the relationship between childhood trauma and perceived relapse tendency (Coeff = 0.049, Boot CI [0.004, 0.121]); interaction of childhood trauma and Baseline RSA negatively influences IIRTV (β = –0.208, t = –2.022, p = .046).Conclusion: The results suggest that males with SUDs who have experienced serious childhood trauma may have executive function impairments that contribute to relapse, and baseline RSA may buffer the negative effect of childhood trauma on IIRTV. These findings suggest that the prevention of relapse through cognitive enhancement can be complemented by the enhancement of physiological regulation.

12 Does Executive Functioning Predict Diagnostic Timing of Autism?

Objective:Executive functioning (EF) is impaired in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), and EF challenges are exacerbated in youth with ASD and ADHD (ASD+ADHD), which may impact diagnostic timing. We hypothesized youth with ASD+ADHD would be more impaired in EF (as opposed to other functional domains) compared to autistic youth without ADHD (ASD-only), with particular deficits in metacognition and inhibition. We also predicted youth with ASD+ADHD would be at significant risk for delayed ASD diagnosis and that greater EF challenges would predict earlier age of ASD diagnosis across groups.Participants and Methods:Data from a clinical database was extracted for 400 youth who received a new diagnosis of ASD after age 5, either with a co-occurring diagnosis of ADHD (ASD+ADHD group: n=297; Mage of ASD diagnosis=10.49; 25.9% female; 48.1% white) or without a co-occurring ADHD diagnosis (ASD-only group: n=100; Mage of ASD diagnosis=12.02; 34.0% female; 44.7% white). EF was measured with the BRIEF-2 parent-report, and ASD symptom strength was measured with the SRS-2 School Age form. Independent samples t-tests investigated whether a) the ASD+ADHD group was uniquely impaired in EF compared to the ASD-only group, b) parents of ASD+ADHD report elevated EF problems, and c) the ASD+ADHD group was at significant risk for delayed ASD diagnosis. Pearson correlations examined the association between age of ASD diagnosis and EF for each diagnostic group. Hierarchical linear regressions further analyzed whether specific EF domains concurrently predicted age of ASD diagnosis, after controlling for the known predictors of assigned sex at birth, FSIQ, and ASD symptom strength.Results:The ASD+ADHD group had greater challenges in overall EF (t=-6.42, p&lt;.001), metacognitive skills (t=-6.47, p &lt;.001), and inhibition skills (t=-7.06, p&lt;.001). There was no significant difference in parent-reported autism symptoms between the ASD and ASD+ADHD groups (t=0.973, p=.331). The ASD+ADHD group received ASD diagnoses earlier than the ASD-only group (t=4.194, p&lt;.001). In the ASD-only group, age of ASD diagnosis was not significantly correlated to overall EF, metacognitive skills, nor inhibition skills (ps&gt;.05). In the ASD+ADHD group, ASD diagnosis was significantly related to overall EF (r(297)=.128, p=.027) and metacognitive skills (r(297)=.329, p&lt;.001) but not inhibition skills (r(297)=.078, p=.180). Hierarchical linear regressions controlling for assigned sex at birth, FSIQ, and SRS-2 T-scores were used to determine whether these EF components significantly predicted age of ASD diagnosis. Overall EF did not predict age of ASD diagnosis in the ASD+ADHD group (ß=.034, t=1.417, p=.157), but metacognitive skills did (ß=.123, t=5.582, p&lt;.001).Conclusions:Our findings suggest youth with ASD+ADHD have greater impairment in overall EF, metacognition, and inhibition compared to ASD-only youth, despite similar levels of ASD traits, consistent with hypotheses. Contrary to our hypothesis, youth with ASD+ADHD in this sample were diagnosed with ASD earlier. However, results also suggest EF problems, specifically metacognitive deficits, predict later age of ASD diagnosis. Future research is needed to replicate findings and better understand how EF and other functional domains predict ASD diagnostic timing.

1 Executive Functioning and Anxiety/Depressive Symptoms as Mediators Between ADHD and Quality of Life: A 10-year Longitudinal Study

Objective:Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with impaired executive functioning and anxiety/depressive symptoms, which may contribute to reduced quality of life. We tested the hypotheses that (1) a childhood diagnosis of ADHD is related to reduced quality of life in emerging adulthood and that (2) this relationship is mediated by impaired executive functioning and anxiety/depressive symptoms.Participants and Methods:We assessed 85 children and adolescents with ADHD and 50 typically developing peers at baseline (Mean age = 11.6 years, 58% males), two-year follow-up, and 10-year follow-up with neuropsychological tests of executive functioning, the Behavioral Rating Inventory of Executive Function (BRIEF), the Short Moods and Feelings Questionnaire (SMFQ), and the Revised Children’s Manifest Anxiety Scale, second edition (RCMAS-2), as well as the Perceived Quality of Life scale (PQoL) at the 10-year follow-up. Four neuropsychological tests of executive functioning, the Letter-Number Sequencing test (working memory), the Color-Word Interference test condition 3 (response inhibition), the Color-Word Interference test condition 4 (shifting), and the trail making test condition 4 (cognitive flexibility) were combined into a neuropsychological executive functioning composite score based on high factor loadings (&gt; .73). the parent-reported BRIEF indexes, the behavioral regulation index, and the metacognition index were used as measures of everyday executive functioning. We conducted independent samples t-tests to compare the groups and simple and parallel mediation analyses with full information maximum likelihood estimation to examine whether the different executive functioning measures and anxiety/depressive symptoms at two-year follow-up mediated the relationship between baseline ADHD and self-reported quality of life at 10-year follow-up.Results:Baseline ADHD was associated with more difficulties with executive functioning on a composite measure of neuropsychological tests (p &lt; .001, Hedges g = .79) and parent-reported everyday metacognitive (p &lt; .001, Hedges g = 2.37) and behavioral regulation executive functioning (p &lt; .001, Hedges g = 1.55), as well as self-reported anxiety (p &lt; .001, Hedges g = 1.05) and depressive symptoms (p &lt; .001, Hedges g = 1.00) at two-year follow-up. Baseline ADHD was associated with lower self-reported quality of life (p = .001, Hedges g = -.67) at 10-year follow-up. The mediation analysis showed that everyday metacognitive executive functioning (p = .011, ß = -.497) and an anxiety/depressive symptoms composite (p &lt; .001, ß = -.404) parallelly mediated the relationship between ADHD and quality of life.Conclusions:Impaired everyday executive functioning and anxiety/depressive symptoms may represent two distinct pathways to reduced quality of life in emerging adults with a childhood diagnosis of ADHD. These findings stress the importance of targeting both cognitive and emotional aspects in interventions for children and adolescents with ADHD to improve later quality of life.

66 Association of Executive Functions and Instrumental Activities of Daily Living in Parkinson’s Disease

Objective:Executive function (EF) abilities tend to decline with age, and disproportionately so for people with neurodegenerative disorders such as Parkinson’s Disease (PD), where EF deficits are commonly seen in the early stages of the disease. Due to their nature, EF are essential for performing tasks of daily life, particularly for the more complex instrumental activities of daily living (IADL), and deficits can impair the ability to execute IADL in PD participants. The aim of this study was to examine how EF impairments relate to IADL deficits in both healthy elderly controls and PD participants.Participants and Methods:Seventy-four participants with idiopathic PD and 66 elderly controls were recruited. All participants were non-demented. A comprehensive neuropsychological assessment was administered including the following measures of EF: Hayling Sentence Completion, Brixton Spatial Anticipation, Trail Making Test A and B, Stroop Color-Word Test, Symbol Span (Wechsler Memory Scale-III), Digit Span (Wechsler Adult Intelligence Scale-III), F-A-S test, and Semantic Fluency (Animals and Actions). Z scores were calculated from respective test manuals. Independence was measured using the 8-item Lawton IADL Scale where items are coded from 0 (dependent) to 1 (independent) and the total score ranges from 0 to 8. Motor impairments were assessed using Part III of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale. Regression models were run with each cognitive measure as the dependent variable, with group (control vs. PD), age, sex, education, and motor severity as predictors, to examine the effect of group on each cognitive variable. Correlations were then run between the total IADL score, demographic variables, and cognitive variables for each participant group separately to identify the relationship between IADL and EF measures.Results:PD participants were predominantly males (n=51, 68.9%), with an average age of 70.64±6.03 and 15.22±2.78 education years. Controls were predominantly female (n=34, 51.5%) and had an average age of 71.19±7.75 and 15.85±2.82 education years. Regarding IADL function, all participants were relatively independent in their IADLs (PD: 7.72±0.69, range 4-8, Controls: 7.98±0.13, range 7-8). The most difficult IADL items for PD participants were shopping (8.2% dependent) and food preparation (12.2% dependent). When correcting for age, education, sex, and motor severity, only the Stroop Interference z-score was significant for participant group (b=0.44, t=2.14, p=0.034), where controls had slightly lower scores (-0.33±0.77) than PD participants (-0.31±0.91). Correlations in controls were significant between IADL total score and Hayling trials 1 (r=0.35, p=0.005) and 2 (r=0.33, p=0.008), and semantic fluency actions trial (r=0.34, p=0.006). In PD participants, IADL total score was only correlated with semantic fluency (animals trial, r=0.26, p=0.028).Conclusions:There were only weak associations between EF abilities and IADL in both healthy controls and PD participants, suggesting that impairments in EF do not necessarily translate into worse ability to execute IADL in PD. More correlations were found in the control group, which may be confounded by the inclusion (in both groups) of participants who already had cognitive impairment. This highlights a further need to examine whether EF impairments in people with PD influence IADL functioning above and beyond normal aging and whether specific deficits have more real-life consequences not attainable through IADL questionnaires.

85 Evaluating the Improvement on the Naturalistic Action Task After the Virtual Kitchen Intervention: A Case Study

Objective:The goal-control model of the functional impairment in dementia posits two different underlying mechanisms: decay of task goals (reduced task accomplishment) and poor control over goal execution (high error rates). Here we present a case series in which we explore the effects of a performance-based, functional intervention on two participants. Outcomes were evaluated using the goal-control framework.Participants and Methods:Two participants with dementia (CS: age 70, 14 years of education; EM: age 93, 18 years of education) completed neuropsychological tests (scored using age, education, and IQ-adjusted norms) and baseline testing with the Naturalistic Action Task (NAT; a validated performance-based task of everyday function including a Breakfast and Lunch task). The Virtual Kitchen (VK) was used to train, through repeated performance, either the Breakfast (CS) or Lunch (EM) tasks for 30 minutes (or 10 total repetitions) per day over 5 days. After VK training, participants performed the NAT Breakfast and Lunch tasks again to evaluate improvement on the trained and untrained tasks. Baseline and post-training NATs were scored for task accomplishment and errors by two coders observing video recordings. Z scores were derived by calculating accomplishment and error change scores for each participant relative to the mean and standard deviations of change scores from a cohort of 36 healthy controls (mean age: 73.3, SD: 6.44; mean education: 17.42, SD: 2.17).Results:Both participants exhibited similar cognitive profiles: high estimated IQ; low MMSE (total = 19 for both CS and EM; 1st percentile); anterograde amnesia, slowed processing speed and impaired executive function; average scores on tests of attention, language, and self-reported depression. Informant report of daily functioning (FAQ) suggested that EM (FAQ=28) exhibited greater functional impairment than CS (FAQ=9). Both participants completed all VK training sessions. Z scores of the change from pre- to post-training showed significant increases in task accomplishment on the trained task (trained condition change z scores: EM = +27.69; CS =+ 6.06), but significantly less improvement or worse task accomplishment on the untrained task (untrained condition change z scores: EM = +4.06; CS = -13.69). The training did not reduce errors, as error rates increased for both participants on the trained task.Conclusions:The participants presented in this case study exhibited comparable cognitive profiles, including marked anterograde amnesia. Our results suggest that repeated training in a virtual context can improve specific aspects of functioning on real, life everyday tasks. Further, according to the goal-control framework, repeated practice reduces the decay of the task goal, as represented by greater task accomplishment, but does not improve executive control over the task execution. Important future directions are to determine if people with different cognitive profiles will demonstrate different benefits from VK training and to examine if virtual training of personally relevant, everyday tasks can promote independent living and improve quality of life.

8 The Battery for Executive Functions in Addiction: Validation of a Novel Screening Tool

Objective:Executive functions (EF) are a primary mediator of both typical and atypical functioning, influencing the progression of psychopathology due to their role in supporting self-monitoring/regulation and top-down control of cognitive processes. According to recent models, EF impairments may contribute to the functional decline of patients with substance use disorder (SUD), exacerbating secondary affective and social symptoms. Despite these potential implications, the tools now commonly used to outline neurocognitive, and specifically EF, impairments in patients with addiction are not tailored to this clinical population, having been developed to assess cognitive or dysexecutive deficits in neurology or geriatric patients. Because of their different clinical focus, such tools are frequently unable to fully delineate the dysfunctional EF profile of addiction patients. We here present the development and validation of a novel specific screening battery for executive disorders in addiction: Battery for Executive Functions in Addiction (BFE-A).Participants and Methods:151 SUD patients and 55 control persons were recruited for the validation of the BFE-A battery. The battery consists of two computerized neurocognitive tasks (Stroop and Go/No-go tasks) and five digitalized neuropsychological tests (focus: short/long-term memory, working memory, focused attention, verbal/non-verbal cognitive flexibility). The tests are designed to assess executive control, inhibition mechanisms, and attention bias toward drugs of abuse.Results:In tests of verbal memory, focused attention, and cognitive flexibility, as well as in computerized tasks, inferential statistical analyses revealed lower performance in SUD patients compared to control participants, indicating a lack of inhibitory processes and dysfunctional management of cognitive resources. The investigation of Cohen’s d values has revealed that inhibitory control, verbal/nonverbal fluency, and short/long-term memory are the areas with the most significant impairments.Conclusions:While the evaluation of EF dysfunctions associated to addiction is a currently underrepresented component of the diagnostic procedure in drug assistance/treatment programs, is also is an essential step for both profiling of patients and design of rehabilitation protocols. Clinical interviews should be complemented by early assessment of cognitive weaknesses and preserved EF skills in order to establishing personalized therapy strategy and perhaps organizing a concurrent phase of cognitive rehabilitation.

Multimodal personalised executive function intervention (E-Fit) for school-aged children with complex congenital heart disease: protocol for a randomised controlled feasibility study

IntroductionChildren with congenital heart disease (CHD) are at risk for executive functions (EF) impairments. To date, interventions have limited effects on EF in children and adolescents with complex CHD. Therefore,...

Abstract 152: Exploring Age‐related Changes in Brain Metabolism among Individuals with Cardiovascular Risk Factors: An FDG‐PET Analysis

Introduction Patients with cognitive impairment often have a history of cardiovascular disease (CVD) or multiple cardiovascular risk factors (CRFs) such as hypertension, obesity, and hypercholesterolemia. The literature reports that CVD with CRFs may increase the risk of developing vascular dementia and Alzheimer’s Disease. 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) allows for the in vivo study of cerebral glucose metabolism, and can detect metabolic alterations in several neurological diseases. As we age, the brain undergoes both structural and functional changes; the regional distribution of these alterations mirrors cognitive decline. This study aims to assess the effect of aging on regional glucose uptake in subjects with known cardiovascular risk factors. Methods In total, 40 subjects (mean age 55.9 ± 11.89 years, 50% males) with known cardiovascular risk factors underwent FDG‐PET scanning, and 70 whole brain structures were analyzed in each subject. Participants were recruited from a group of patients with chest pain syndromes who were referred for coronary CT angiography. All subjects underwent whole‐body FDG‐PET/CT imaging 180 minutes after the administration of 4.0 MBq/kg dose of FDG. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). MIMneuro provides region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Pearson’s R was calculated and evaluated for significance in all variables. The threshold for significance was set at P &lt; 0.05. Results Various significant associations between age and FDG uptake across all 70 brain regions of interest were observed. In particular, age was found to have an inverse correlation with regional metabolism in the middle temporal gyrus (r= ‐0.364, p=0.021), superior frontal gyrus (r= ‐0.433, p=0.005), superior parietal lobule (r= ‐0.354, p=0.025), supplementary motor area (r= ‐0.436, p=0.005), and temporal operculum (r= ‐0.370, p=0.019). Conclusion The results demonstrate a significant inverse correlation between age and FDG uptake in five regions among individuals with cardiovascular risk factors. This information may be useful in the determination of whether such scans might be useful in the evaluation of patients with a history of CVD/CRF or with mild cognitive impairment (MCI). Previous literature has reported that increased medial temporal gyrus atrophy is a predictor of dementia in subjects with MCI, and alterations within this lobe mark the beginning of the disease process. Our strongest inverse correlation, the superior frontal gyrus, has been shown to be related to working memory; hypometabolism in this region has previously correlated with severity of cognitive impairments in attention, executive function, and language. Further research is needed to determine the potential for using FDG‐PET imaging as a tool for early detection and intervention for cognitive decline. If patients with CVD or CRFs can be properly diagnosed, if there exists a metabolic signature of regional functional change, intervention may prove highly beneficial for cognitive function, quality of life, and overall well‐being.

4 Relationships Between Task-Switching Performance and Adaptive Behavior Outcomes in Survivors of Pediatric Brain Tumor

Objective:Survivors of pediatric brain tumor (BT) experience impaired executive function (EF) and adaptive behavior (i.e. the ability to complete daily living tasks independently). The literature hypothesizes that executive dysfunction contributes to suboptimal adaptive behavior outcomes in BT survivors; however, the aspects of EF that drive this relationship remain unexplored. Task-switching is an EF component that involves switching between concurrently presented tasks. This skill is critical for many day-to-day activities and may therefore contribute to observed adaptive functioning difficulties. This study investigates relationships between performance on two task-switching measures and adaptive behavior outcomes in BT survivors compared to healthy controls.Participants and Methods:86 survivors of pediatric BT (Mage(SD)= 23.42(4.24), 44 females) and 86 age- and sex-matched controls (Mage(SD) = 23.09(4.40), 44 females) from the Atlanta area completed the Delis-Kaplan Executive Function System Trail Making Test (TMT) and Verbal Fluency Test (VFT). Respectively, the Letter-Number Sequencing (LNS) and Category Switching (CS) conditions were isolated as measures of task-switching. Baseline conditions, representing the foundational skills needed to perform these timed task-switching measures rapidly (TMT: Letter Sequencing, Number Sequencing; VFT: Category Fluency), were included as covariates in all regressions. Informants familiar with the participants’ daily living were interviewed with the Scales of Independent Behavior-Revised (SIB-R) to measure adaptive behavior in four domains (Motor Skills, Social Communication, Personal Living, Community Living). Linear regressions and t-tests confirmed group differences on task-switching performance and on adaptive functioning outcomes, respectively. Then, linear regressions investigated relationships between performance on each task-switching measure (LNS, CS) and SIB-R scores for survivors. A group by task-switching interaction was added to directly explore group differences in these relationships. α=.0125 was used due to Bonferroni correction for the four SIB-R comparisons within each task-switching measure.Results:BT survivors were more impaired than controls on LNS, CS, and SIB-R scores (p&lt;.05, except Personal Living p=.058). For TMT, decreased performance on LNS predicted lower SIB-R scores in Social Communication (p=.001, r2semipartial=.14), Personal Living (p=.002, r2semipartial=.13), and Community Living (p=.003, r2semipartial =.11), but not Motor Skills (p=.184) in BT survivors. Strength of significant relationships was greater for survivors than controls (all p&lt;.002). For VFT, decreased performance on CS predicted lower SIB-R scores in Personal Living (p=.036, r2semipartial =.06) and Community Living (p=.04, r2semipartial =.05), but not in Motor Skills (p=.716) or Social Communication (p=.14) in BT survivors. Positive relationships between CS and SIB-R scores for all 4 domains were greater in survivors than controls (p&lt;.0125).Conclusions:These findings reveal a robust, positive relationship between task-switching performance and independent, daily behaviors that is specific to BT survivors. The relationship between LNS and Motor Skills may have been weakened by covariates involving baseline motor abilities; however, CS results suggest that task-switching is important for motor skills in survivors relative to controls. Community living skills were impaired in survivors and consistently related to task-switching performance. This work may inform interventions to target task-switching abilities and consequently, promote everyday living skills. Interventions aimed at vulnerabilities in adaptive behavior may help increase independence and quality-of-life as survivors transition to adulthood.

Sociodemography, pattern, and response inhibition in suicide survivors: A case-control study.

Suicide is a global phenomenon. Psychiatric disorders are estimated to contribute to a large proportion of suicides; however, impulsive suicide is also common. Among the ages of 15-29 years, suicide was the second leading cause of death worldwide and has been hypothesized to have reduced response inhibition and decision-making abilities as contributing factors, which directly relate to impaired executive functioning and suicidal behavior. This study aimed to study sociodemography, method, and pattern of suicide, and response inhibition in suicide survivors. A case-control study was designed in a tertiary medical center in Madhya Pradesh using convenient sampling of suicide survivors and controls from the general population over 3 months. Data collection was semi-structured pro forma, and response inhibition was assessed using the Stroop test. Statistical analysis was performed using IBM Statistical Package for the Social Sciences (SPSS) Windows version 25.0. Independent-samples Student's t-test, Chi-square test, and Mann-Whitney U-test were used for analyzing means of continuous data, nominal data, and ordinal data, respectively. The level of significance was at P < 0.05. A total of 126 suicide survivors and 99 controls were assessed after the end of the study period. Age (mean age for cases 25.4 ± 9.16; controls 23 ± 7.9), gender (F ~ M), and socioeconomic status were used to match cases and controls. 85.7% of suicide survivors had no history of suicide, but the majority had precipitating factors. Anomic suicide was the most common type, and poisoning was the most common method of suicide. Response inhibition between cases and control was significantly different. The majority of suicide attempts were impulsive in youth, with no gender discrimination. Response inhibition seemed to play a role in a suicide attempt.

1 Predictors of Neurocognitive Outcome in Pediatric Ischemic and Hemorrhagic Stroke

Objective:Neurocognitive deficits commonly occur following pediatric stroke and can impact many neuropsychological domains. Despite awareness of these deleterious effects, neurocognitive outcome after pediatric stroke, especially hemorrhagic stroke, is understudied. This clinical study aimed to elucidate the impact of eight factors identified in the scientific literature as possible predictors of neurocognitive outcome following pediatric stroke: age at stroke, stroke type (i.e., ischemic vs. hemorrhagic), lesion size, lesion location (i.e., brain region, structures impacted, and laterality), time since stroke, neurologic severity, seizures post-stroke, and socioeconomic status.Participants and Methods:Ninety-two patients, ages six to 25 and with a history of pediatric stroke, chose to participate in the study and were administered standardized neuropsychological tests assessing verbal reasoning, abstract reasoning, working memory, processing speed, attention, learning ability, long-term memory, and visuomotor integration. A standardized parent questionnaire provided an estimate of executive functioning. Statistical analyses included spline regressions to examine the impact of age at stroke and lesion size, further divided by stroke type; a series of one-way analysis of variance to examine differences in variables with three levels; Welch’s t-tests to examine dichotomous variables; and simple linear regressions for continuous variables.Results:Lesion size, stroke type, age at stroke, and socioeconomic status were identified as predictors of neurocognitive outcome in our sample. Large lesions were associated with worse neurocognitive outcomes compared to small to medium lesions across neurocognitive domains. Exploratory spline regressions suggested that ischemic stroke was associated with worse neurocognitive outcomes than hemorrhagic stroke. Based on patterns shown in graphs, age at stroke appeared to have an impact on outcome depending on the neurocognitive domain and stroke type, with U-shaped trends suggesting worse outcome across most domains when stroke occurred at approximately 5 to 10 years of age. Socioeconomic status positively predicted outcomes across most neurocognitive domains. Participants with seizures had more severe executive functioning impairments than youth without seizures. Youth with combined cortical-subcortical lesions scored lower on abstract reasoning than youth with cortical and youth with subcortical lesions, and lower on attention than youth with cortical lesions. Neurologic severity predicted scores on abstract reasoning, attention, processing speed, and visuomotor integration, depending on stroke type. There was no evidence of differences on outcome measures based on time since stroke, lesion laterality, or lesion region defined as supra-versus infratentorial.Conclusions:The current study contributed to the scientific literature by identifying lesion size, stroke type, age at stroke, and socioeconomic status as predictors of neurocognitive outcome following pediatric stroke. Future research should examine other possible predictors of neurocognitive outcome that remain unexplored. Multisite collaborations would provide larger sample sizes and allow teams to build models with better statistical power and more predictors. Enhancing understanding of neurocognitive outcomes following pediatric stroke is a first step towards improving appraisals of prognosis.Findings are clinically applicable as they provide professionals with information that can help assess individual expected patterns of recovery and thus refer patients to appropriate support services.

24 Adaptive Functioning and Academic Achievement in Survivors of Childhood Acute Lymphoblastic Leukemia

Objective:Executive functioning (EF) and socioeconomic status (SES) are associated with functional outcomes (adaptive functioning and academic achievement) in healthy controls and pediatric populations with executive dysfunction. However, these relationships have yet to be investigated in survivors of childhood acute lymphoblastic leukemia (ALL), a population with EF impairment resulting from disease and treatment characteristics. The objective of this study was to examine the associations of functional outcomes with EF and SES (neighborhood-specific variables and academic support) in survivors of childhood ALL.Participants and Methods:Forty-four participants (38.6% female, 72.7% non-Hispanic White, ages 6-17) previously diagnosed with low-risk or standard-risk pre-B cell ALL and treated with chemotherapy-only were included. Participants were evaluated on performance-based measures of EF (cognitive flexibility, verbal fluency, working memory, and processing speed) and academic achievement (word reading and math calculation), and parent-ratings of EF and adaptive functioning. All measures were expressed as T-scores with lower scores indicating better performance. Neighborhood-specific variables were based on participants’ zip codes and census block group, and included area deprivation index (ADI) and child opportunity index (COI). Lower ADI and COI indicate lesser deprivation and greater opportunity. Individualized education plan (IEP) status was used as a proxy of academic support, coded dichotomously as with or without IEP. Percentages of participants showing impairments in functional outcomes were calculated using a cutoff of &gt; 1 SD above the normative mean. Partial correlations were conducted while controlling for age at evaluation, age at diagnosis, sex, and verbal IQ, to examine whether participants with poorer performance-based and parent-rated EF would show reduced functional outcomes. Multiple regression analyses were conducted to evaluate whether neighborhood-specific variables and IEP status would predict functional outcomes while controlling for covariates.Results:Compared to population norms, survivors of childhood ALL showed worse functional outcomes. Within adaptive functioning, 45.5% of participants showed impairment in activities of daily living and leadership. Adaptive functioning was significantly positively correlated with parent-rated, but not performance-based, EF (r=0.694, p&lt;0.001). Compared to female survivors, male survivors were at increased risk for adaptive functioning difficulties (r=-0.401, p&lt;0.05). Impairments for word reading and math calculation were 25% and 41.7%, respectively. Greater math calculation was associated with better verbal fluency (r=0.378, p&lt;0.05) and processing speed (r=0.439, p&lt;0.05). Older participants at evaluation (/3=-0.580, p&lt;0.001) and those without IEP support (ß=0.465, p&lt;0.05) showed better word reading. Lower ADI predicted better verbal fluency (ß=0.282, p=0.041), however, neighborhood-specific variables were not associated with functional outcomes.Conclusions:Prior findings indicate that performance-based measures and parent-ratings assess different constructs of EF. Thus, adaptive functioning may relate more to the behavioral construct of EF than its cognitive construct. Current findings also suggest that male survivors are at increased risk for reduced adaptive functioning, consistent with recent reports that male survivors of ALL are at greater risk for specific neurocognitive outcomes. Overall, functional outcomes may be more strongly related to EF than neighborhood-specific variables. Long-term goals include early screening of adaptive and academic difficulties, targeted intervention, and neuropsychological monitoring to support pediatric survivors’ neurocognitive and psychosocial development.

Risk factors for violent behaviour before and after the onset of schizophrenia spectrum disorder: A naturalistic case-control study in the Netherlands

BackgroundRisk factors for violent behaviour may differ depending on whether this begins before (VBO) or after (VAO) the onset of schizophrenia spectrum disorder. However, previous studies have been limited by selective samples of forensic patients and crude outcome measures. MethodsThe sample consisted of 1013 patients with schizophrenia spectrum disorders recruited from various treatment settings across the Netherlands. Putative risk factors and outcomes were measured with standardised instruments. We used logistic regression models to compare patients with VBO (n = 48), patients with VAO (n = 130) and nonviolent (NV) patients (n = 708) on each risk factor, adjusting for sex and age. ResultsPatients with VBO more often lived in a socially disorganised neighbourhood than NV patients (adjusted odds ratio [aOR] 3.3, 95 % confidence interval [CI] 1.3–8.0) and patients with VAO (aOR 3.3, 95 % CI 1.1–9.6). Clinical risk factors were more prevalent in patients with VAO than in NV patients, with substance misuse (aOR 1.5, 95 % CI 1.0–2.3), impairments in executive functions (aOR 1.6, 95 % CI 1.0–2.4), poor impulse control (aOR 2.4, 9 % CI 1.5–3.6), delusions (aOR 1.5, 95 % CI 1.1–2.3) and lack of illness insight (aOR 1.5, 95 % CI 1.0–2.2) reaching statistical significance. Patients with VBO were also more likely to have poor impulse control than NV patients (aOR 2.6, 95 % CI 1.3–5.1). ConclusionStrategies to predict and prevent violence in schizophrenia spectrum disorders should distinguish between VBO and VAO.

High burdens of phosphorylated tau protein and distinct precuneus atrophy in sporadic early-onset Alzheimer’s disease

Early-onset Alzheimer’s disease (EOAD) is a rare devastating subclassification of Alzheimer’s disease (AD). EOAD affects individuals <65 years old, and accounts for 5%–10% of all AD cases. Previous studies on EOAD primarily focused on familial forms, whereas research on sporadic EOAD (sEOAD), which represents 85%–90% of EOAD cases, is limited. In this prospective cohort study, participants were recruited between 2018 and 2023 and included patients with sEOAD (n = 110), late-onset AD (LOAD, n = 89), young controls (YC, n = 50), and older controls (OC, n = 25). All AD patients fulfilled the diagnostic criteria based on biomarker evidence. Familial EOAD patients or non-AD dementia patients were excluded. Single molecule array technology was used to measure fluid biomarkers, including cerebrospinal fluid (CSF) and plasma amyloid beta (Aβ) 40, Aβ42, phosphorylated tau (P-tau) 181, total tau (T-tau), serum neurofilament light chain and glial fibrillary acidic protein (GFAP). Patients with sEOAD exhibited more severe executive function impairment and bilateral precuneus atrophy (P < 0.05, family-wise error corrected) than patients with LOAD. Patients with sEOAD showed elevated CSF and plasma P-tau181 levels (154.0 ± 81.2 pg/mL, P = 0.002; and 6.1 ± 2.3 pg/mL, P = 0.046). Moreover, precuneus atrophy was significantly correlated with serum GFAP levels in sEOAD (P < 0.001). Serum GFAP levels (area under the curve (AUC) = 96.0%, cutoff value = 154.3 pg/mL) displayed excellent diagnostic value in distinguishing sEOAD patients from the control group. These preliminary findings highlight the crucial role of tau protein phosphorylation in the pathogenesis and progression of sEOAD.