The Adolescent Transplant Recipient: An Overview of Neurocognitive Functioning and Implications for Long-Term Outcomes.

BACKGROUND: Solid organ transplantation (SOT) offers improved long-term survival for youth with end-stage organ disease. From a neurodevelopmental, cognitive, and academic perspective, children with solid organ transplant have a number of unique risk factors. While cognitive functioning may improve post-transplantation, it is important to understand the trajectory of neurocognitive development starting in transplant candidacy to evaluate the implications of early deficits. AIM: The aim of this paper is to describe the neurocognitive risks and long-term implications for adolescent transplant recipients. METHOD: This paper provides an overview of neurocognitive functioning in youth with end-stage organ dysfunction with discussion of implications for adolescent transplant recipients. RESULTS: Post-transplant, adolescent, and young adult solid organ transplant recipients exhibit significant levels of executive dysfunction, with implications for decision-making, regimen adherence, and transition to adult transplant care. CONCLUSION: Transplantation may reduce the risk for poor long-term neurocognitive effects, yet adolescent transplant recipients remain at increased risk, particularly in executive functioning, which has implications for adherence and transition to adulthood. Baseline and follow-up assessments for youth with end-stage organ disease and transplant are important for the monitoring of neurocognitive development and may be used to mitigate risk for low adherence to post-transplantation treatment regimens and reduce barriers to transitioning to adult transplant care.

Individualized trajectories in postradiotherapy neurocognitive functioning of patients with brain metastases.

Background: The increasing incidence of brain metastases (BMs) and improved survival rates underscore the necessity to investigate the effects of treatments on individuals. The aim of this study was to evaluate the individual trajectories of subjective and objective cognitive performance after radiotherapy in patients with BMs. Methods: The study population consisted of adult patients with BMs referred for radiotherapy. A semi-structured interview and comprehensive neurocognitive assessment (NCA) were used to assess both subjective and objective cognitive performance before, 3 months and ≥ 11 months after radiotherapy. Reliable change indices were used to identify individual, clinically meaningful changes. Results: Thirty-six patients completed the 3-month follow-up, and 14 patients completed the ≥ 11-months follow-up. Depending on the domain, subjective cognitive decline was reported by 11-22% of patients. In total, 50% of patients reported subjective decline in at least one cognitive domain. Intracranial progression 3 months postradiotherapy was a risk-factor for self-reported deterioration (P = .031). Objective changes were observed across all domains, with a particular vulnerability for decline in memory at 3 months postradiotherapy. The majority of patients (81%) experienced both a deterioration as well as improvement (eg, mixed response) in objective cognitive functioning. Results were similar for the long-term follow-up (3 to ≥11 months). No risk factors for objective cognitive change 3 months postradiotherapy were identified. Conclusions: Our study revealed that the majority of patients with BMs will show a mixed cognitive response following radiotherapy, reflecting the complex impact. This underscores the importance of patient-tailored NCAs 3 months postradiotherapy to guide optimal rehabilitation strategies.

A preliminary study on the neurocognitive deficits associated with loneliness in young adults.

The experience of loneliness is universal and may have an adverse effect on neurocognitive functioning even at a younger age. Using a comprehensive neurocognitive functioning test (NCFT) battery, we examined the possible negative effects of loneliness on neurocognitive functioning in young adults. The high-loneliness and low-loneliness groups were screened using the UCLA Loneliness Scale v. 3, and measures pertaining to the domains of intelligence, attention, memory, executive function, and psychomotor functioning were tested and compared. As depression and anxiety were significantly higher in the high-loneliness group, an analysis of covariance was conducted. As a result, the high-loneliness group showed significantly poor performance on measures of executive function and attention prior to controlling for depression and anxiety, and executive function retained its significance even after controlling for these variables. Additional analysis showed that depression and anxiety did not significantly mediate the relationship between loneliness and neurocognitive functioning. Such results suggest that loneliness is likely to negatively affect executive functioning and attention in early adulthood and then progressively spread to other domains of cognitive functioning, as reported in the older adult population. The limitations and implications of the present study were considered and addressed.

Health-related quality of life and neurocognitive functioning in patients with recurrent glioblastoma treated with intracerebral immune checkpoint inhibition.

PURPOSE: After glioblastoma (GB) recurrence, prognosis is very cumbersome. Therefore, health-related quality of life (HRQoL) and neurocognitive functioning (NCF) have become important endpoints in clinical trials when evaluating novel treatments. We aimed to evaluate the HRQoL and NCF in patients with recurrent glioblastoma (rGB) treated with a combination of surgical intervention (reoperation or biopsy) and intracerebral immune checkpoint inhibition. METHODS: Patients who participated in the trial (N = 23), at a single-center university hospital were included. Data were collected using 3 patient-reported outcome measures (EORTC-QLQ-C30, EORTC-QLQ-BN20, and HADS) and computerized NCF testing. In the responder group, baseline values were compared to results at a 6-month follow-up. Additionally, exploratory analyses compared baseline HRQoL and NCF between responders and non-responders. RESULTS: There were five responders and 18 non-responders. When comparing the mean and individual baseline with follow-up results for the responders, we observed overall a stable to slight clinically relevant improvement of HRQoL in multiple subsets of the questionnaires while maintaining a stable NCF. One patient deteriorated on anxiety and depression symptoms from baseline to follow-up. CONCLUSIONS: In patients that responded to intracerebral immunotherapy in our institutional trial, HRQoL and NCF remained stable over time, suggesting that no detrimental effect on cognitive function or quality of life may be expected with this treatment approach. Furthermore, there seems to be an overall tendency for responders to score better on HRQoL and NCF than non-responders at baseline.

Differential sensitivity of intraindividual variability dispersion and global cognition in the prediction of functional outcomes and mortality in precariously housed and homeless adults.

OBJECTIVE: To examine cognitive intraindividual variability (IIV) dispersion as a predictor of everyday functioning and mortality in persons who are homeless or precariously housed. METHOD: Participants were 407 community-dwelling adults, followed for up to 13 years. Neurocognition was assessed at baseline and IIV dispersion was derived using a battery of standardized tests. Functional outcomes (social, physical) were obtained at baseline and last follow-up. Mortality was confirmed with Coroner's reports and hospital records (N = 103 deaths). Linear regressions were used to predict current social and physical functioning from IIV dispersion. Repeated measures Analysis of Covariance were used to predict long-term change in functioning. Cox regression models examined the relation between IIV dispersion and mortality. Covariates included global cognition (i.e. mean-level performance), age, education, and physical comorbidities. RESULTS: Higher IIV dispersion predicted poorer current physical functioning (B = -0.46 p = .010), while higher global cognition predicted better current (B = 0.21, p = .015) and change in social functioning over a period of up to 13 years (F = 4.23, p = .040). Global cognition, but not IIV dispersion, predicted mortality in individuals under 55 years old (HR = 0.50, p = .013). CONCLUSIONS: Our findings suggest that indices of neurocognitive functioning (i.e. IIV dispersion and global cognition) may be differentially related to discrete dimensions of functional outcomes in an at-risk population. IIV dispersion may be a complimentary marker of emergent physical health dysfunction in precariously housed adults and may be best used in conjunction with traditional neuropsychological indices.

Psychopathology as long-term sequelae of maltreatment and socioeconomic disadvantage: Neurocognitive development perspectives.

Neuroscience research underscores the critical impact of adverse experiences on brain development. Yet, there is limited understanding of the specific pathways linking adverse experiences to accelerated or delayed brain development and their ultimate contributions to psychopathology. Here, we present new longitudinal data demonstrating that neurocognitive functioning during adolescence, as affected by adverse experiences, predicts psychopathology during young adulthood. The sample included 167 participants (52% male) assessed in adolescence and young adulthood. Adverse experiences were measured by early maltreatment experiences and low family socioeconomic status. Cognitive control was assessed by neural activation and behavioral performance during the Multi-Source Interference Task. Psychopathology was measured by self-reported internalizing and externalizing symptomatology. Results indicated that higher maltreatment predicted heightened frontoparietal activation during cognitive control, indicating delayed neurodevelopment, which, in turn predicted higher internalizing and externalizing symptomatology. Furthermore, higher maltreatment predicted a steeper decline in frontoparietal activation across adolescence, indicating neural plasticity in cognitive control-related brain development, which was associated with lower internalizing symptomatology. Our results elucidate the crucial role of neurocognitive development in the processes linking adverse experiences and psychopathology. Implications of the findings and directions for future research on the effects of adverse experiences on brain development are discussed.

Gender disparities in neuropsychological assessment research in drug abuse populations: A systematic review.

Objective: To systematically review the literature on the neurocognitive effects of drug use to determine if there are significant gender differences. Methods: In April 2023, we conducted a broad search in MEDLINE (via PubMed), PsycINFO, and Embase for original research studies that used objective neuropsychological assessment to evaluate neurocognition in persons with drug use. Data extraction was performed in a masked, duplicate fashion. Results: Our initial search returned 22,430 records, of which 273 articles were included in our analysis. We found significant underrepresentation of women as participants in the studies. Twenty-one percent of studies had exclusively male participants; when women were included, they averaged only 23% of the sample. Only 49 studies sufficiently documented an analysis of their results by gender; due to the heterogeneity in study characteristics, no conclusions about cognitive differences between women and men could be made. Conclusions: Women are significantly underrepresented in the research on cognition in drug use. Increased efforts to include more women participants and consistent analysis and reporting of data for potential gender differences will be required to close this gap in knowledge, which may lead to improved substance abuse treatment approaches for women.

State-level working memory and dysregulated eating in children and adolescents: An exploratory ecological momentary assessment study.

BACKGROUND: Children with loss of control (LOC) eating and overweight/obesity have relative deficiencies in trait-level working memory (WM), which may limit adaptive responding to intra- and extra-personal cues related to eating. Understanding of how WM performance relates to eating behavior in real-time is currently limited. METHODS: We studied 32 youth (ages 10-17 years) with LOC eating and overweight/obesity (LOC-OW; n = 9), overweight/obesity only (OW; n = 16), and non-overweight status (NW; n = 7). Youth completed spatial and numerical WM tasks requiring varying degrees of cognitive effort and reported on their eating behavior daily for 14 days via smartphone-based ecological momentary assessment. Linear mixed effects models estimated group-level differences in WM performance, as well as associations between contemporaneously completed measures of WM and dysregulated eating. RESULTS: LOC-OW were less accurate on numerical WM tasks compared to OW and NW (ps < .01); groups did not differ on spatial task accuracy (p = .41). Adjusting for between-subject effects (reflecting differences between individuals in their mean WM performance and its association with eating behavior), within-subject effects (reflecting variations in moment-to-moment associations) revealed that more accurate responding on the less demanding numerical WM task, compared to one's own average, was associated with greater overeating severity across the full sample (p = .013). There were no associations between WM performance and LOC eating severity (ps > .05). CONCLUSIONS: Youth with LOC eating and overweight/obesity demonstrated difficulties mentally retaining and manipulating numerical information in daily life, replicating prior laboratory-based research. Overeating may be related to improved WM, regardless of LOC status, but temporality and causality should be further explored. PUBLIC SIGNIFICANCE STATEMENT: Our findings suggest that youth with loss of control eating and overweight/obesity may experience difficulties mentally retaining and manipulating numerical information in daily life relative to their peers with overweight/obesity and normal-weight status, which may contribute to the maintenance of dysregulated eating and/or elevated body weight. However, it is unclear whether these individual differences are related to eating behavior on a moment-to-moment basis.

Effects of Bumetanide on Neurocognitive Functioning in Children with Autism Spectrum Disorder: Secondary Analysis of a Randomized Placebo-Controlled Trial.

We present the secondary-analysis of neurocognitive tests in the 'Bumetanide in Autism Medication and Biomarker' (BAMBI;EUDRA-CT-2014-001560-35) study, a randomized double-blind placebo-controlled (1:1) trial testing 3-months bumetanide treatment (≤ 1 mg twice-daily) in unmedicated children 7-15 years with ASD. Children with IQ ≥ 70 were analyzed for baseline deficits and treatment-effects on the intention-to-treat-population with generalized-linear-models, principal component analysis and network analysis. Ninety-two children were allocated to treatment and 83 eligible for analyses. Heterogeneous neurocognitive impairments were found that were unaffected by bumetanide treatment. Network analysis showed higher modularity after treatment (mean difference:-0.165, 95%CI:-0.317 to - 0.013,p = .034) and changes in the relative importance of response inhibition in the neurocognitive network (mean difference:-0.037, 95%CI:-0.073 to - 0.001,p = .042). This study offers perspectives to include neurocognitive tests in ASD trials.

Different profiles of neurocognitive functioning in patients with brain metastases prior to brain radiotherapy.

OBJECTIVE: Patients with brain metastases (BrMs) are a heterogeneous population, with almost 50% experiencing cognitive impairment before brain radiotherapy. Defining pre-radiotherapy cognitive profiles will aid in understanding of the cognitive vulnerabilities and offer valuable insight and guidance for tailoring interventions. METHODS: The study population consisted of 58 adult patients with BrMs referred for radiotherapy. A semi-structured interview and comprehensive battery including 10 neuropsychological tests were used to assess subjective and objective cognitive performance prior to radiotherapy. RESULTS: A majority (69%) of patients report decline in cognitive performance compared to their premorbid level (i.e. pre-cancer). Objective testing revealed memory (52%), processing speed (33%) and emotion recognition (29%) deficits were most frequent. 21% of patients had no cognitive deficits while 55% had deficits (-1.5SD) in at least two cognitive domains. Hierarchical cluster analysis based on patient deficit profiles identified four clusters: (I) no or limited cognitive deficits selectively restricted to processing speed or executive function, (II) psychomotor speed deficits, (III) memory deficits and (IV) extensive cognitive deficits including memory. No patient or clinical-related (e.g. age, number of BrMs, previous treatment) differences were found between clusters. CONCLUSIONS: Patterns of cognitive performance in patients with BrMs are heterogeneous, with most experiencing at least some degree of neurocognitive dysfunction. We identified four meaningful cognitive clusters. Stability of these clusters over time and in different samples should be assessed to advance understanding of the cognitive vulnerability of this patient population.

Executive Control and Associated Brain Activity in Children With Familial High-Risk of Schizophrenia or Bipolar Disorder: A Danish Register-based Study.

BACKGROUND AND HYPOTHESES: Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children. STUDY DESIGN: Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study-VIA 11. STUDY RESULTS: We included 85 (44% female) FHR-SZ, 63 (52% female) FHR-BP and 98 (50% female) PBC in the analyses. Executive control effects, caused by the spatial visuomotor conflict, showed no differences between groups. Bayesian ANOVA of reaction time (RT) variability, quantified by the coefficient of variation (CVRT), revealed a group effect with similarly higher CVRT in FHR-BP and FHR-SZ compared to PBC (BF10 = 6.82). The fMRI analyses revealed no evidence for between-group differences in task-related brain activation. Post hoc analyses excluding children with psychiatric illness yielded same results. CONCLUSION: FHR-SZ and FHR-BP at age 11-12 show intact ability to resolve a spatial visuomotor conflict and neural efficacy. The increased variability in RT may reflect difficulties in maintaining sustained attention. Since variability in RT was independent of existing psychiatric illness, it may reflect a potential endophenotypic marker of risk.

Examining the influence of pain and fatigue on neurocognitive functioning in adolescents and young adults with sickle cell disease.

Pain and fatigue are among the most common and impactful complications of sickle cell disease (SCD). Individuals with SCD are also more likely to have neurocognitive deficits. Previous studies have suggested that pain and fatigue might influence neurocognitive functioning in patients with SCD. However, these studies are limited by small sample sizes and inadequate measurement of cognitive performance. The present study aimed to investigate the relationship between pain and fatigue with neurocognitive functioning using performance-based measures of neurocognition. Pain and fatigue were not associated with neurocognitive performance. Implications and directions for future research are discussed.

Neurocognitive and clinical characteristics of elementary school-aged children with a history of suicidal thoughts and behaviors.

BACKGROUND: Suicidal thoughts and behaviors (STBs) in elementary school-aged youth have increased in recent years. Understanding the risks associated with childhood STBs is necessary for prevention efforts. METHODS: The current study examined clinical and neurocognitive characteristics of a community sample of elementary school-aged children with (STB+) and without (STB-) a history of STBs. The final sample included 93 families with children average age of 7.8 years (SD = 1.3). Children in this sample were racially diverse, evenly split by sex, and most identified as non-Hispanic. Neurocognitive functioning was assessed using computerized behavioral measures. Child clinical characteristics were assessed using self-report measures and STB history was assessed using semi-structured interviews. RESULTS: Of the 93 families, 64 STB- children and 29 STB+ children participated. On average, STB+ children were older, reported higher levels of depressive and anxiety symptoms, and were more likely to have a parental history of suicidal behavior (PH+). Regarding neurocognitive functioning, STB+ children exhibited lower raw scores for both the NIH Dimensional Change Card Sort Task (NIH-DCCS) and NIH Flanker Inhibitory Control and Attention Test (NIH-Flanker). Multivariable regression analyses revealed raw scores for NIH-DCCS and NIH-Flanker, PH+ status, and child age were associated with childhood STBs. LIMITATIONS: Prospective data is needed to confirm cross-sectional findings. CONCLUSIONS: Poorer neurocognitive functioning and PH+ status may serve as risk markers for STBs in elementary school-aged children. Targeting prevention programming for these risks may reduce the likelihood of STBs in at-risk elementary school-aged youth.

Anomalous self-experiences and neurocognitive functioning in adolescents at risk for psychosis: Still no significant associations found between these two vulnerability markers.

BACKGROUND: Anomalous self-experiences (ASEs) and neurocognitive impairments are considered essential domains of vulnerability for developing psychotic disorders. However, little research exists of possible associations between ASEs and neurocognitive functions in individuals at-risk for psychosis. The interconnections between ASEs and neurocognitive impairments should therefore be clarified as much as possible, especially in young individuals at risk. No previous studies have investigated these two fundamental domains in non-help-seeking adolescents at risk for developing psychosis. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). Adolescents (N = 48, 94% females, mean age = 15.3) were invited to participate after completing a 14-year-old survey distributed by MoBA. At-risk adolescents were selected based on the 0.4% highest scores on 19 items assessing both psychotic-like experiences and ASEs. Five specifically selected and formulated items measuring ASEs were computed to an ASEs total score. Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery. RESULTS: Regression analyses revealed no significant relationships between ASEs and any neurocognitive domain. CONCLUSIONS: We did not find any significant associations between ASEs and neurocognitive functions in non-help-seeking adolescents at risk for psychotic disorders, which is in line with reports from other types of cohorts. Thus, ASEs and neurocognitive functions may be understood as two relatively separate domains that co-exist in at-risk states. These results underline the need for a wider scope when making predictions about future trajectories, e.g. the development of psychotic disorders. Including both ASEs and neurocognitive functioning in at-risk populations may increase the specificity of vulnerability criteria in this population and enhance our understanding of early psychosis psychopathology.

Can circadian rhythm predict changes in neurocognitive functioning in bipolar disorder: protocol of a 12-month longitudinal cohort study based on research domain criteria.

Introduction: Bipolar disorder (BD) is a prevalent and disabling mental disorder characterized by disrupted circadian rhythms and impaired neurocognitive features, both of which fall under the major domains of Research Domain Criteria (RDoC). However, there is limited evidence regarding the interaction between circadian rhythms and long-term neurocognitive functioning. Therefore, this longitudinal cohort study protocol aims to explore whether circadian rhythm can predict changes in neurocognitive functioning over time in patients with BD.Methods: This study adopts a longitudinal cohort design, aiming to recruit 100 BD patients in either depressive or remitted states. Participants will undergo evaluations from clinical, circadian rhythm, and neurocognitive perspectives at baseline, 6-month, and 12-month follow-ups, involving questionnaires, actigraphy, and computed neurocognitive tests. We will examine both cross-sectional and longitudinal associations between participants' circadian rhythm patterns and neurocognitive functioning. Statistical analyses will employ Spearman correlation and mixed regression models.Discussion: We anticipate that circadian rhythms may serve as predictors of neurocognitive functioning changes. The findings of this study could offer supplementary insights into BD pathophysiology, potential treatment targets, and prediction.Trial Registration: This study has been registered with the Chinese Clinical Trial Registry under the registration code ChiCTR2200064922 on 21st October 2022.

Mobile Assessments of Mood, Cognition, Smartphone-Based Sensor Activity, and Variability in Craving and Substance Use in Patients With Substance Use Disorders in Norway: Prospective Observational Feasibility Study.

BACKGROUND: Patients with substance use disorders (SUDs) are at increased risk for symptom deterioration following treatment, with up to 60% resuming substance use within the first year posttreatment. Substance use craving together with cognitive and mental health variables play important roles in the understanding of the trajectories from abstinence to substance use. OBJECTIVE: This prospective observational feasibility study aims to improve our understanding of specific profiles of variables explaining SUD symptom deterioration, in particular, how individual variability in mental health, cognitive functioning, and smartphone use is associated with craving and substance use in a young adult clinical population. METHODS: In this pilot study, 26 patients with SUDs were included at about 2 weeks prior to discharge from inpatient SUD treatment from 3 different treatment facilities in Norway. Patients underwent baseline neuropsychological and mental health assessments; they were equipped with smartwatches and they downloaded an app for mobile sensor data collection in their smartphones. Every 2 days for up to 8 weeks, the patients were administered mobile ecological momentary assessments (EMAs) to evaluate substance use, craving, mental health, cognition, and a mobile Go/NoGo performance task. Repeated EMAs as well as the smartphone's battery use data were averaged across all days per individual and used as candidate input variables together with the baseline measures in models of craving intensity and the occurrence of any substance use episodes. RESULTS: A total of 455 momentary assessments were completed out of a potential maximum of 728 assessments. Using EMA and baseline data as candidate input variables and craving and substance use as responses, model selection identified mean craving intensity as the most important predictor of having one or more substance use episodes and with variabilities in self-reported impulsivity, mental health, and battery use as significant explanatory variables of craving intensity. CONCLUSIONS: This prospective observational feasibility study adds novelty by collecting high-intensity data for a considerable period of time, including mental health data, mobile cognitive assessments, and mobile sensor data. Our study also contributes to our knowledge about a clinical population with the most severe SUD presentations in a vulnerable period during and after discharge from inpatient treatment. We confirmed the importance of variability in cognitive function and mood in explaining variability in craving and that smartphone usage may possibly add to this understanding. Further, we found that craving intensity is an important explanatory variable in understanding substance use episodes.

Prospective, longitudinal study to isolate the impacts of marijuana use on neurocognitive functioning in adolescents.

Introduction: Policies to legalize possession and use of marijuana have been increasingly supported across the United States. Although there are restrictions on use in minors, many substance abuse scientists anticipate that these policy changes may alter use patterns among adolescents due to its wider availability and a softening of beliefs about its potentially harmful consequences. Despite the possibility that these policies may increase the prevalence of use among adolescents, the effects of marijuana on neurodevelopment remain unclear, clouding arguments in favor of or opposition to these policies. Methods: The present prospective, longitudinal study was designed to isolate the neurodevelopmental consequences of marijuana use from its precursors during adolescence-a period of heightened vulnerability for both substance use and disrupted development due to environmental insults. Early adolescents who were substance-naïve at baseline (N = 529, aged 10-12) were recruited and tracked into adolescence when a subgroup initiated marijuana use during one of three subsequent waves of data collection, approximately 18 months apart. Results: Results suggest that marijuana use may be specifically related to a decline in verbal learning ability in the short term and in emotion recognition, attention, and inhibition in the longer-term. Discussion: These preliminary findings suggest that marijuana use has potential to adversely impact vulnerable neurodevelopmental processes during adolescence. Intensive additional investigation is recommended given that state-level policies regulating marijuana use and possession are rapidly shifting in the absence of good scientific information.

Neurocognitive functioning in comorbid insomnia and sleep apnea patients is better after positive airway pressure therapy, but worse after cognitive behavioral therapy for insomnia: exploratory analysis of cognitive outcomes from the Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea study.

STUDY OBJECTIVES: Neurocognitive impairments in comorbid insomnia and sleep apnea (COMISA) are not well documented. We explored neurocognitive functioning and treatment effects in individuals with COMISA as an ancillary study to a randomized clinical trial. METHODS: Participants with COMISA (n = 45; 51.1% female; mean age = 52.07 ± 13.29 years), from a 3-arm randomized clinical trial combining cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) concurrently (CBT-I+PAP) or sequentially, completed neurocognitive testing at baseline, and post-treatment. Using Bayesian linear mixed models, we estimated effects of CBT-I, PAP, or CBT-I+PAP, compared to baseline, and CBT-I+PAP compared to PAP on 12 metrics across five cognitive domains. RESULTS: This COMISA sample had worse neurocognitive performance at baseline than reported for insomnia, sleep apnea, and controls in the literature, though short-term memory and psychomotor speed performance appears intact. When comparing PAP to baseline, performance on all measures was better after treatment. Performance after CBT-I was worse compared to baseline, and only performance in attention/vigilance, executive functioning via Stroop interference and verbal memory was better with moderate-high effect sizes and moderate probability of superiority (61-83). Comparisons of CBT-I+PAP to baseline generated results similar to PAP and comparing CBT-I+PAP to PAP revealed superior performance in only attention/vigilance via psychomotor vigilance task lapses and verbal memory for PAP. CONCLUSIONS: Treatment combinations involving CBT-I were associated with poorer neurocognitive performance. These potentially temporary effects may stem from sleep restriction, a component of CBT-I often accompanied by initially reduced total sleep time. Future studies should examine long-term effects of individual and combined COMISA treatment pathways to inform treatment recommendations. CLINICAL TRIAL: This was an ancillary study from a clinical trial (Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS), which was preregistered at www.clinicaltrials.gov (NCT01785303)).

Long-Term Follow-Up of Daily Life Functioning After Pediatric Intensive Care Unit Admission.

OBJECTIVE: To investigate the long-term impact of pediatric intensive care unit (PICU) admission on daily life functioning while exploring the potential mediating role of neurocognitive outcome. STUDY DESIGN: This cross-sectional observational study compared children aged 6-12 years with previous PICU admission (age ≤1 year) for bronchiolitis requiring mechanical ventilation ("patient group," n = 65) to demographically comparable healthy peers ("control group," n = 76). The patient group was selected because bronchiolitis is not expected to affect neurocognitive functioning in itself. Assessed daily life outcome domains were behavioral and emotional functioning, academic performance, and health-related quality of life (QoL). The role of neurocognitive outcomes in the relationship between PICU admission and daily life functioning was assessed by mediation analysis. RESULTS: The patient group did not differ from the control group regarding behavioral and emotional functioning but performed poorer on academic performance and school-related QoL (Ps ≤ .04, d = -0.48 to -0.26). Within the patient group, lower full-scale IQ (FSIQ) was associated with poorer academic performance and school-related QoL (Ps ≤ .02). Poorer verbal memory was associated with poorer spelling performance (P = .002). FSIQ mediated the observed effects of PICU admission on reading comprehension and arithmetic performance. CONCLUSIONS: Children admitted to the PICU are at risk for long-term adverse daily life outcomes in terms of academic performance and school-related QoL. Findings suggest that lower intelligence may contribute to academic difficulties after PICU admission. Findings underline the importance of monitoring daily life and neurocognitive functioning after PICU admission.

Association between objective neurocognitive functioning and neurocognitive complaints in recurrent high-grade glioma: Longitudinal evidence of cognitive awareness from EORTC brain tumour trials.

BACKGROUND: Patients' reduced awareness of neurocognitive functioning (NCF) may negatively affect the reliability of patient-reported outcomes (PROs) and clinical decision-making. This study evaluated cognitive awareness, defined as the association between NCF and neurocognitive complaints, over the disease course of patients with recurrent high-grade glioma (HGG). METHODS: We assessed NCF using the EORTC core clinical trial battery and neurocognitive complaints using the Medical Outcome Study questionnaire. Patients were categorised as impaired or intact, based on their neurocognitive performance. Spearman's rank correlations were calculated between NCF and neurocognitive complaints at baseline and each 12 weeks, until 36. The association between changes in NCF and neurocognitive complaints scores between these follow-up assessments was determined using Pearson's correlation. RESULTS: A total of 546 patients were included. Neurocognitively impaired patients (n = 437) had more neurocognitive complaints (range: 10.51 [p < 0.001] to 13.34 [p = 0.001]) than intact patients (n = 109) at baseline, at 12 and 24 weeks. In intact patients, NCF and neurocognitive complaints were correlated for only one domain at baseline (0.202, p = 0.036), while in impaired patients correlations were more frequently found in various domains and time points (range: 0.164 [p = 0.001] to 0.334 [p = 0.011]). Over the disease course, NCF and neurocognitive complaints were correlated for only one domain at baseline (0.357, p = 0.014) in intact patients while in impaired patients they were correlated for more domains and time points (range: 0.222 [p < 0.001] to 0.366 [p < 0.001]). CONCLUSION: Neurocognitively impaired patients with recurrent HGG are aware of their neurocognitive limitations at study entry and during follow-up, which should be considered in clinical decision-making and when interpreting PRO results.