Neurocognitive Function Research Articles

8.G. Scientific session: The German National Cohort (NAKO): Current state, follow up data collection and selected results

Abstract This workshop aims to give an overview on current state and selected results of the German National Cohort (NAKO). NAKO is the largest, multidisciplinary population-based cohort study in Germany. The overall aims of NAKO are: 1) to elucidate pathways to major chronic diseases such as diabetes, cancer, cardiovascular, pulmonary, neuro-psychiatric, and infectious diseases, focusing on determinants and exposures (e.g., socioeconomic, psychosocial, behavioural, occupational, and environmental factors); 2) to assess regional differences; and to improve prevention and early detection of disease. Between 2014 and 2019 more than 205,000 men and women aged 20-74 years at baseline were recruited in 18 study centres across Germany. During their examination participants underwent an extensive programme including a face-to-face interview, self-administered, computer-based questionnaires, in-depth biomedical examinations, and the collection of various bio-samples. In addition, at 5 study centres a subgroup of almost 31,000, received whole-body magnet resonance imaging (MRI). In 4-5 year intervals, all study participants are re-invited for examination at the study centres. The first re-examination started in October 2018 and will be finished in July 2024. In parallel the pilot phase for the second re-examination will start in May 2024. The programme for both re-examinations is similar to the baseline programme. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. During the COVID-19 pandemic two supplemental questionnaires focusing on pandemic-related aspects were provided to all NAKO participants at two different time points. The first COVID-19 questionnaire collected data on more than 160,000 participants during the first COVID-19-related lockdown in Spring 2020. The questionnaire included questions on general state of health, Sars-CoV-2 symptoms, changes in psychosocial, socioeconomic, and behavioural factors (e.g., physical activity). The workshop session consists of four presentations. The first presentation will provide insights into the extensive examination programme of NAKO, will give a short overview on the current state and plans for follow-up of data collection. In addition, it will briefly inform about possibilities to get access to NAKO data. Furthermore, the workshop will include three presentations on selected results of NAKO to demonstrate its broad research scope. The presentations will focus on the following topics: 1) cardiovascular disease and sex differences according to socioeconomic position, 2) cognitive functioning according to income, employment and living alone, 3) physical activity and changes during the COVID-19 pandemic. Key messages • Due to the large sample size, and the broad research scope, NAKO provides an excellent resource to scientists form different research disciplines and enforces interdisciplinary collaborations. • The workshop will be informative to researchers who are planning to work with NAKO data as data access within the European Union/the European Economic Area is open since spring 2024.

Relationship between intracranial pressure and neurocognitive function among older adults after radical resection of rectal cancer

Relationship between intracranial pressure and neurocognitive function among older adults after radical resection of rectal cancer

A Comparative Analysis of Neurocognitive Function in Community- and Hospital-Based Patients With Schizophrenia.

The study compared differences in various neurocognitive characteristics across treatment modalities among schizophrenia patients recruited in one city between July 2020 and June 2023 who were on regular medication. Of the 151 participants, 113 were included in the analysis. Participants were divided into community-based and hospital-based groups, and their demographics and clinical characteristics, including insight, quality of life, positive and negative symptoms, and personal and social functioning, were examined. In addition, several aspects of cognition were assessed using neurocognitive assessments such as the Trail Making Test (TMT), Stroop test, and Wisconsin Card Sorting Test (WCST). After adjusting for age differences between groups, the final analysis included data from 42 participants in the community-based group and 33 participants in the hospital-based group. Hospital-based group participants completed Stroop-W more rapidly, excelled in Rey-Osterrieth Complex Figure Test recall and recognition, and incurred fewer TMT Part B (TMT-B) and Stroop-C errors. Additionally, they outperformed in WCST total, non-persistent errors, and categories completed. Contrastingly, community-based group participants showed superior outcomes in WCST persistent responses and errors, suggesting specific neurocognitive strengths. We found differences in neurocognitive characteristics between the two groups. These differences were consistent across a range of cognitive domains, including attention, visual discrimination, memory, and executive functioning. Further large-scale study is needed to generalize cognitive characteristics across treatment modalities.

Impact of switching from EFV/F/TDF to B/F/TAF on psychiatric symptoms and neurocognition.

The aim was to investigate whether switching from EFV/F/TDF to B/F/TAF may improve neuropsychiatrc symptoms and neurocognition. Pilot, single-arm, prospective study of persons with HIV (PWH) on the efficacy and safety of switching from EFV/F/TDF to B/F/TAF. Participants underwent neuropsychological assessment (NPA) at switch (T0) and after 48 weeks (T1). NPA was carried out through a standardized battery of 12 tests. Neurocognitive impairment (NCI) was defined by a score ≥1 standard deviation (SD) below the normal mean on at least 2 tests or ≥2 SD below on 1 test. Individual z-scores were determined, NPZ-12 was calculated as the average of 12 test z-scores and change of NPZ-12 was the outcome. HIV-associated Neurocognitive Disorder (HAND) was classified by Frascati's criteria. Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), and Pittsburgh Sleep Quality Index (PSQI) were administered. Paired-Wilcoxon and McNemar tests were used for comparisons, and logistic regression for associations with NCI changes. Out of 126 participants, BAI, BDI-II, and PSQI questionnaires revealed an improvement at T1. NPA revealed NCI in 40.5% of persons at T0 and 42.1% at T1 (p = 0.746). Specifically, at T0, among participants with NCI, 35% improved; among those without, 26% worsened at T1; NPZ-12 score worsened at T1. 5.6% of ANI was observed at T0 and 7.9% at T1. No factor associated with these changes was found. Our results suggest switching from EFV/F/TDF to B/F/TAF significantly improves psychiatric symptoms and sleep quality. Neurocognitive performance remained stable, although a decline in NPZ-12 and in specific domains was observed.

Factors Contributing to Variability in Neurocognitive Performance Before Glioma Neurosurgery

Abstract Background Cognitive impairment following anti-tumor treatment is a common concern for brain tumor patients. However, growing evidence indicates that significant impairments can be present even before treatment. The purpose of this study was to identify factors that explain variability in pre-treatment test performance, beyond that of tumor burden. Methods Using multi-step linear regression, we retrospectively probed the contribution of clinical-, tumor-, patient-, and self-reported factors to variance in performance among 96 treatment-naïve brain tumor patients across 13 objective neurocognitive tests. Agreement between subjective and objective reports of cognitive impairment was also examined. Results Clinically significant pre-operative impairments were observed in both objective and subjective domains. Estimated premorbid intelligence quotient (IQ), tumor volume, diagnosis of an astrocytoma, self-reported Depression and perceived Cognitive Functioning Scores were the most common predictors of objective neurocognitive performance prior to treatment, explaining 12.3%-58.3% of the variance. No association was identified between objective and subjective reports of cognitive impairment. Conclusions Glioma patients frequently exhibit objective and subjective impairments prior to treatment. Both tumor- and self-reported factors were identified as predictors of performance, after correcting for estimated premorbid IQ. Nevertheless, more than 41.7% of the variance in cognitive performance remained unexplained, indicating a substantial role for additional, as yet unaccounted for, clinical factors. Notable disparity between objective- and subjective cognitive impairment status re-emphasizes the importance of assessing both domains to ascertain a patient’s overall functioning in the context of treatment outcomes.

Neurocognitive functioning during adolescence: Spanish validation of the Penn Computerized Neurocognitive Battery.

The Penn Computerized Neurocognitive Battery - Child Version (PennCNB-cv) is presented as a brief tool that allows comprehensive and automated assessment of 5 factors (via 14 performance tasks): Executive Control, Episodic Memory, Complex Cognition, Social Cognition, and Sensorimotor Speed. The literature links (dys)functions in these areas with psycho(patho)logical constructs, but evidence is scarce among Spanish-speaking youth. Therefore, this study aims to validate the PennCNB-cv in a community sample of Spanish adolescents. After a process of (back)translation and adaptation by bilingual researchers, the PennCNB-cv was administered in 34 schools. The sample included1506 students, ages 14-19, 44.28% were male. Preliminary treatment of the data included descriptive and correlational statistics. To provide evidence of structural validity, exploratory and confirmatory factor analyses were performed. Results from the exploratory and confirmatory factor analysis showed a four-factor model (Complex Cognition, Executive Control, Episodic Memory, and Social Cognition) as the most appropriate.These findings provide compelling evidence in favor of the a priori theory that underpinned the development​ of the CNB. The study of the psychometric properties showed that the Spanish version of the PennCNB-cv, seems to be an adequate tool for assessing neurocognitive functioning during adolescence.

EEG Oscillatory Activity and Resting-State Networks Associated with Neurocognitive Function in Mild Traumatic Brain Injury.

This study aimed to investigate the characteristics of resting-state electroencephalography (EEG) activity and brain networks in patients with mild traumatic brain injury (mTBI) and their association with neurocognitive function (NCF). We analyzed 26 patients with subacute mTBI and 21 healthy controls. The subacute mTBI group (9 females, 17 males) had a mean age of 29.9 ± 9.9 years, and the healthy controls (11 females, 10 males) had a mean age of 29.7 ± 11.5 years. Current source density, lagged phase synchronization, and resting-state network activity were analyzed using exact low-resolution electromagnetic tomography (eLORETA) with 60 s resting-state EEG data. In addition, a correlation analysis was performed between these EEG parameters and NCF in patients with mTBI. We used the statistical nonparametric mapping method in eLORETA to correct for multiple comparisons. There were no significant differences in EEG parameters between the patients with mTBI and healthy controls. However, in patients with mTBI, correlation analysis revealed negative correlations between theta activity in the anterior cingulate cortex and verbal short-term memory and between activity in the memory perception network and verbal memory. Our findings suggest that resting-state EEG may be clinically useful in investigating the mechanism of NCF decline in patients with mTBI.

Associations Between High-Density Lipoprotein Cholesterol Efflux and Brain Grey Matter Volume.

Objective: High-density lipoprotein cholesterol efflux function may prevent brain amyloid beta deposition and neurodegeneration. However, the relevance of this finding has not been established in the diverse middle-aged population. Methods: We examined 1826 adults (47% Black adults) who participated in the Dallas Heart Study to determine associations between high-density lipoprotein (HDL) measures and brain structure and function. White matter hyperintensities (WMH) and whole-brain grey matter volume (GMV) were measured using brain MRI, and the Montreal Cognitive Assessment (MoCA) was used to measure neurocognitive function. HDL cholesterol efflux capacity (HDL-CEC) was assessed using fluorescence-labeled cholesterol efflux from J774 macrophages, and HDL particle size measures were assessed using nuclear magnetic resonance (NMR) spectroscopy (LipoScience). Multivariable linear regressions were performed to elucidate associations between HDL-CEC and brain and cognitive phenotypes after adjustment for traditional risk factors such as age, smoking status, time spent in daily physical activity, and education level. Results: Higher HDL-CEC and small HDL particle (HDL-P) concentration were positively associated with higher GMV normalized to total cranial volume (TCV) (GMV/TCV) after adjustment for relevant risk factors (β = 0.078 [95% CI: 0.029, 0.126], p = 0.002, and β = 0.063 [95% CI: 0.014, 0.111], p = 0.012, respectively). Conversely, there were no associations between HDL measures and WMH or MoCA (all p > 0.05). Associations of HDL-CEC and small HDL-P with GMV/TCV were not modified by ApoE-ε4 status or race/ethnicity. Interpretation: Higher HDL cholesterol efflux and higher plasma concentration of small HDL-P were associated with higher GMV/TCV. Additional studies are needed to explore the potential neuroprotective functions of HDL.

Acute Ketone Monoester Supplementation in Young Adults: Modulating Metabolic and Neurocognitive Functions Across Body Weights.

This study investigated the acute effects of ketone monoester on metabolic and neurocognitive indicators and underlying metabolism-brain-cognition interactions among young adults of healthy weight (HW) and those with overweight/obesity (OW). Forty participants were divided into two groups: HW (n = 20, age 23.80±3.96 years, body mass index [BMI] 21.49±1.80 kg/m²) and OW (n = 20, age 22.00±2.13 years, BMI 28.23±3.48 kg/m²). Each participant completed two trials (ketone monoester vs. placebo, 395 mg/kg dose) in a randomized order. Metabolic indicators (blood beta-hydroxybutyrate [BHB] and glucose) and neurocognitive function (causal density via functional near-infrared spectroscopy and cognitive interference via the Stroop task) were measured at baseline, 30 minutes, and 90 minutes post-supplementation. A chain mediation model was constructed to test the indirect effects of BHB level on cognitive interference through mediators like blood glucose and causal density. In the linear mixed models, significant effects were observed for trial (β = -0.92, 0.20, -0.04, 25.53) and assessment time (β = 0.50, -0.14, 0.09, -62.88) in BHB, glucose, causal density, and cognitive interference (p < 0.05), but not for group factors. Compared to OW, the effects of ketone monoester on prefrontal connectomes were more enduring in the HW (p < 0.05). Elevated BHB level improved cognitive function through decreasing glucose level and increasing causal density, with estimate of -0.63. Acute ketone monoester supplementation elevated levels of blood BHB and prefrontal connectomes and decreased levels of glucose and cognitive interference, regardless of weight status. Elevated blood BHB enhanced cognitive function through multi-tiered neurometabolic pathways.

Diagnostic Accuracy of Neurocognitive and Executive Functions to Discriminate Women With and Without Fibromyalgia Syndrome: A Secondary Analysis.

Objective: The aim of the current study was to determine the capability of neurocognitive variables and executive functions to differentiate women with and without fibromyalgia syndrome (FMS). Methods: A secondary diagnostic accuracy analysis was conducted. A battery of neurocognitive and executive function tests (the D2 Attention test, the Rey-Osterrieth Complex Figure for visual perception, "Digits D/R/I" tests of the WAIS-IV battery for working memory, the 5-Digit test for mental inhibition, the Symbol Search for processing speed, and the Zoo Test for planning/decision-making) were collected in 129 women with FMS and 111 without FMS. The area under the receiver operating characteristic (ROC) curve, optimal cut-off point, sensitivity, specificity, and positive and negative likelihood ratios (LR) for each variable were calculated. Results: Between-group differences were identified in ROCF_Copy (p = 0.043), ROCF_Recall (p = 0.004), d2_TR (p = 0.019), d2_TA (p = 0.007), d2_TOT (p = 0.005), d2_CON (p = 0.004), d2_C (p = 0.042), Symbol Search (p = 0.008), Decoding _FDT (p = 0.001), Retrieving_FDT (p = 0.001), and Inhibiting_FDT (p = 0.024). The result showed that FDT-based outcomes (Retrieving_FDT: ROC 0.739, sensitivity 85.3%, specificity 48.6%; Decoding_FDT: ROC 0.724, sensitivity 50.4%, specificity 16.2%; Inhibiting_FDT: ROC 0.708, sensitivity 56.6%, specificity 22.5%) were the variables able to differentiate between women with and without FMS. Conclusions: Although women with FMS exhibited deficits in attention, long-term visual memory, processing speed, and mental inhibition when compared with women without FMS, only mental inhibition scores showed moderate diagnostic accuracy to discriminate between women with and without FMS. Future studies investigating these results in clinical settings are needed to identify the clinical relevance of these findings.

Mitochondrial DNA copy number and neurocognitive outcomes in children.

Low mitochondria DNA copy number (mtDNAcn) has been linked to cognitive decline. However, the role of mtDNAcn in healthy cognitive development is unclear. We hypothesized early-life mtDNAcn would be associated with children's learning and memory. We quantified mtDNAcn in umbilical cord blood and child blood at ages 5-7 from participants in a prospective birth cohort. We administered the Children's Memory Scale (CMS) at ages 9-14 (N = 342) and the Wechsler Intelligence Scale for Children (WISC-IV) at ages 7 and 9 (N = 457). Associations between mtDNAcn tertiles and CMS and WISC were evaluated with linear regression and linear mixed-effects models, respectively. We examined non-linear associations using generalized additive mixed models. Relative to the middle tertile of mtDNAcn, lower childhood mtDNAcn was associated with lower WISC Working Memory (β = -2.65, 95% CI [-5.24, -0.06]) and Full-Scale IQ (β = -3.71 [-6.42, -1.00]), and higher CMS Visual Memory (β = 4.70 [0.47, 8.93]). Higher childhood mtDNAcn was linked to higher CMS Verbal Memory (β = 7.75 [2.50, 13.01]). In non-linear models, higher childhood mtDNAcn was associated with lower WISC Verbal Comprehension. Our study provides novel evidence that mtDNAcn measured in childhood is associated with children's neurocognitive performance. mtDNAcn may be a marker of healthy child development. Mitochondrial DNA copy number (mtDNAcn) may serve as a biomarker for early-life neurocognitive performances in the children's population. Both low and high mtDNAcn may contribute to poorer neurocognition, reflected through learning and memory abilities. This research elucidated the importance of investigating mitochondrial biomarkers in healthy populations and facilitated advancements of future studies to better understand the associations between mitochondrial markers and adverse children's health outcomes.

Surgical treatment of meningiomas improves neurocognitive functioning and quality of life – a prospective single-center study

Background and purposeEarly diagnosis and the refinement of treatment of patients with intracranial meningiomas have brought quality of life (QoL) and neurocognitive functioning as outcome measures into focus. The aim of this study is a comprehensive assessment of neurocognitive function, quality of life and the presence of depression in meningioma patients before and after surgery.MethodsPatients with MRI diagnosis of intracranial meningioma and indication for surgery were prospectively included. A clinical neuropsychologist performed neurocognitive assessments within 3 months before and 12 months after surgery. The test battery included investigation of selective and divided attention, verbal and figural memory, executive functioning, and word fluency. Self-report questionnaires to assess depressive symptoms, QoL, and disease coping were administered. Raw values and t-values were compared pre-and postoperatively. Outcome was stratified by tumor- and peritumoral brain edema (PTBE) volumes, postoperative resolution of PTBE and WHO grade. The study included 18 predominantly female patients (83%) with a median age of 59 years and mostly CNS WHO grade 1 meningiomas (83%).ResultsThere was a significant postoperative improvement in the ability to selectively react under stress, in working memory and improved delayed reproduction of verbal and visual memory content. QoL improved regarding a reduction in physical problems, an improvement in energy, and social functioning. There was a trend towards worse preoperative scores in all tests, and greater postoperative improvement in patients with PTBE. Tumor volume had no effect on the measured outcome. The patients did not suffer from depressive symptoms before the surgery but improved postoperatively and most patients had an active, problem-oriented coping strategy.ConclusionResection of intracranial meningiomas leads to an improvement in multiple neurocognitive domains and QoL. There is a trend towards poorer preoperative neurocognitive functioning and greater postoperative improvement in patients with PTBE. Depression appears to play a minor role in the context of neurocognitive functioning and disease coping.

12566 Adult Growth Hormone Deficiency, Replacement Therapy Use, and IGF1 Levels in Association with Physical, Psychosocial, and Neurocognitive Outcomes Among Childhood Cancer Survivors

Abstract Disclosure: T. Yoshida: None. J.L. Baedke: None. H. Wang: None. C.H. Yu: None. C.L. Wilson: None. D.A. Mulrooney: None. S.B. Dixon: None. I. Huang: None. T.M. Brinkman: None. K.R. Krull: None. S. Mostoufi-Moab: None. J. Miguel Martínez: None. K.K. Ness: None. M.M. Hudson: None. Y. Yasui: None. A. Delaney: None. Background: Adult growth hormone deficiency (aGHD) is a common and often untreated late effect among childhood cancer survivors. Untreated aGHD likely adds to the burden of health outcomes in survivors already experiencing cancer treatment related late toxicities. As comprehensive data on the consequences of untreated aGHD in survivors are scarce, we assessed the clinical impact of untreated aGHD among survivors, together with socioeconomic factors as potential contributing factors, utilizing a large, clinically characterized cohort of childhood cancer survivors. Methods: 3902 five-year survivors ≥ 18 years old [median (25th-75th percentile) age, 31.7y (25.2-40.0); age at cancer diagnosis 8.1y (3.5-13.6); 47.5% female] were examined. We assessed the: 1) proportion of survivors with aGHD on GH therapy (GHT); 2) association between GHT and socioeconomic factors (e.g., household income, area deprivation index) by multivariable logistic regression; and 3) associations between age- and sex-adjusted insulin-like growth factor 1 (IGF1) z-score and prevalence of clinically-assessed (i.e., body composition, metabolic/cardiovascular factors, neurocognitive function) and self-reported [i.e., quality of life (QoL), emotional symptom] outcomes by multivariable logistic regression with trend test, adjusting for potential confounders (e.g., radiation to the hypothalamic-pituitary region). Results: aGHD was observed in 9.1% (354/3902) of survivors; among them, 9.0% (32/354) were on GHT. Survivors on GHT were more likely to have higher household income, hold health insurance, and reside in less socioeconomically disadvantaged neighborhoods, compared to survivors with untreated aGHD. Socioeconomic factors had significant independent associations with GHT use in multivariable analysis [e.g., annual household income &amp;lt;$40,000 vs. ≥$80,000, adjusted odds ratio (aOR) of GHT use, 0.28; 95% confidence interval (CI), 0.08-0.86]. Lower IGF1 z-score (IGF1 z-score ≤ -2, vs. IGF1 z-score &amp;gt;0) was associated with a higher prevalence of various outcomes (aOR, 95% CI), such as abdominal obesity (2.56, 1.98-5.26), weak handgrip strength (2.49, 1.65-3.73), hypertension (1.47, 1.06-2.04), abnormal glucose metabolism (2.07, 1.49-2.86), impaired health-related QoL (e.g., physical functioning, 1.97, 1.35-2.86), depression (1.58, 1.06-2.33), and impairment in multiple neurocognitive functions (e.g., verbal reasoning, a global measure of intelligence, 2.22, 1.49-3.30) with a dose-response relationship. Conclusions: Our data support a negative impact of untreated aGHD on physical, psychosocial, and neurocognitive outcomes among survivors and suggest the potential of GHT to improve QoL of survivors with aGHD. As lower socioeconomic status may affect survivors’ access to GHT, this disparity should be considered in interventions evaluating GHT for survivors with aGHD. Presentation: 6/3/2024

7494 Glycerol Phenylbutyrate Treatment of Two Patients with Monocarboxylate Transporter 8 Deficiency

Abstract Disclosure: A. Zung: None. N. Sonntag: None. U. Schweizer: None. E. Banne: None. D. Braun: None. Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Currently, the two thyromimetic agents 3,5-diiodothyropropionic acid (DITPA) and triiodothyroacetic acid (TRIAC) have been evaluated in the treatment of these patients, as they both partially restore intracellular TH action independent of MCT8. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. Objective: We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. Methods: We treated two monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, serum markers of peripheral hyperthyroidism, vital signs, anthropometric measurements and neurocognitive functions by several neurodevelopment validated tests. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In-vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P32[1]L mutation. Results: NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment yielded a dose-dependent decrease in FT3 and an increase in FT4 serum levels. The patients showed an elevation in cholesterol levels in parallel with GPB dose, but sex-hormone binding protein (SHBG), another marker of peripheral hyperthyroidism was not affected. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neuro-cognitive improvement was observed, mainly in hyperreflexia score, slight improvement in gross motor functions and a mild progression in cognitive functions. Serum metabolites of GPB did not exceed the toxic range but elevated liver transaminases restricted the dose intensification of GPB. Conclusions: In the first report of GPB treatment in MCT8 deficiency patients we found an improvement in TH profile and body-mass index (BMI). The reduction in T3 levels could contribute to the remarkable increase in BMI-SDS, since various aspects of peripheral hyperthyroidism in MCT8 deficiency, including poor weight gain, were attributed to elevated T3. The limited effects of GPB treatment on cognitive and motor functions can derive from the advanced age of the patients at the time of the intervention. Presentation: 6/2/2024

7912 Children's Neurodevelopmental Outcomes at School-Age After Conception with Hysterosalpingography Using Iodinated Contrast Media

Abstract Disclosure: S. Keestra: None. C. Kooper: None. N. van Welie: None. K. Dreyer: Grant Recipient; Self; research grants from Guerbet. Speaker; Self; travel and speaker fees Guerbet. R. van Eekelen: None. T. Roseboom: None. J. Oosterlaan: None. B. Mol: Consulting Fee; Self; Organon Laboratories, Norgine, Merck. Grant Recipient; Self; Merck. Stock Owner; Self; ObsEva. M. Finken: None. V. Mijatovic: Grant Recipient; Self; Guerbet, Merck, Ferring Pharmaceuticals. Speaker; Self; Guerbet, Merck, Ferring Pharmaceuticals. M. Königs: None. Thyroid hormone sufficiency in pregnancy is vital for children's neurodevelopment. Exposure to iodine excess can cause transient disruption of thyroid hormone synthesis through the Wolff-Chaikoff effect. Iodinated contrast media are commonly utilized in hysterosalpingography (HSG) as part of female fertility work-up. When conception occurs shortly after HSG with iodinated contrast, a temporary reduction of maternal and/or foetal thyroid hormone synthesis could jeopardize children's neurodevelopment. We compared the neurodevelopmental outcomes of 6-9-year-old children (n=69) conceived &amp;lt;6 months after HSG with 5-10 ml of oil-based contrast (iodine content: 480mg/ml) or water-based contrasts (iodine content: 250mg/ml) in the follow-up of a nationwide randomised controlled trial (H2Oil trial; Netherlands; 2012-2014; NCT05168228). A community sample of naturally-conceived children (n=44) with similar age, sex and parental education was used as a comparison group (NTR9574). Primary outcomes were intelligence (Wechsler’s Intelligence Scale for Children V), behaviour questionnaires for parents and teachers (Strengths and Difficulties Questionnaire (SDQ); Strengths and Weaknesses of ADHD Symptoms And Normal behaviour (SWAN)), and academic performance. Secondary outcomes were neurocognitive domains assessed in computerized tasks focussing on Processing &amp; Control, Verbal Memory, Visual Memory, Verbal Working Memory, Visual Working Memory, and Visuomotor Integration (Emma Toolbox for Neurocognitive Functioning). We adjusted linear regression models for age, sex, and parental education, applying FDR correction for multiple comparisons. Additional analysis looked at children conceived within 4 weeks, 4-12 weeks, or &amp;gt;12 weeks after HSG. Children conceived &amp;lt;6 months after HSG had lower performance on intelligence tests (-6.81; 95%CI -10.97 to -2.65; p=0.02) and the neurocognitive domain Processing &amp; Control (-0.52; 95%CI-0.84 to -0.19; p=0.02), with processing speed and consistency affected. No differences were found for other neurocognitive domains, behaviour or academic performance. In comparison to naturally-conceived children, children conceived &amp;lt;4 weeks after HSG had lower performance on intelligence tests, but there was no difference for children conceived 4-12 weeks and &amp;gt;12 weeks after HSG. Replication studies with higher power are needed to further evaluate the safety of iodinated contrast media use periconception, including their effects on thyroid function and children's neurodevelopment. Closer monitoring and treatment of thyroid dysfunction in the months following HSG may be warranted. Presentation: 6/1/2024

Assessment of Adaptive Functioning and the Impact ofSeizures in KBG Syndrome.

This study aimed to examine the adaptive functioning status and the impact of epileptic seizures on neurocognitive outcomes in KBG syndrome, a rare genetic neurodevelopmental disorder characterized by pathogenic variants in ANKRD11. A single clinician interviewed individuals and families with genetically confirmed cases of KBG syndrome. Trained professionals also conducted assessments using the Vineland-3 Adaptive Behavior Scales. The assessment covered the domains of communication, daily living skills, socialization, and maladaptive behaviors, and then compared individuals with and without epilepsy. Further comparisons were made with data from interviews and participants' medical records. Thirty-nine individuals (22 males, 17 females) with KBG syndrome, confirmed through genetic analysis, were interviewed via videoconferencing, followed by Vineland-3 assessment by trained raters. Individuals with KBG syndrome came from 36 unique families spanning 11 countries. While the KBG cohort displayed lower overall adaptive behavior composite scores compared with the average population, several members displayed standard scores at or higher than average, as well as higher scores compared with those with the neurodevelopmental disorder Ogden syndrome. Within the KBG cohort, males consistently scored lower than females across all domains, but none of these categories reached statistical significance. While the group with epilepsy exhibited overall lower scores than the nonseizure group in every category, statistical significance was only reached in the written communication subdomain. Our research provides insights that can aid in epilepsy screening and inform assessment strategies for neurocognitive functioning in those with this condition. The cohort performed overall higher than expected, with outliers existing in both directions. Although our results suggest that seizures might influence the trajectory of KBG syndrome, the approaching but overall absence of statistical significance between study groups underscores the need for a more extensive cohort to discern subtle variations in functioning.

Sex matters: Differences in prodromes, clinical and neuropsychological features in individuals with a first episode mania or psychosis

ObjectiveThis study was aimed at identifying sex differences in patients presenting a first episode mania (FEM) or psychosis (FEP) to help shaping early treatment strategies focused on sex differences. MethodsPatients with a FEM or FEP underwent a clinical, neuropsychological (neurocognitive functions and emotional intelligence) and functional assessment. Performance on those variables was compared between groups through general linear model, with sex and group (FEM vs FEP) as main effects and group by sex interactions. ResultsThe total sample included 113 patients: FEM = 72 (45.83 % females) and FEP = 41 (46.34 % females). There were significant main effects for group (not for sex) for most of the clinical features (depressive, negative and positive symptoms) and psychosocial functioning (χ2 = 8.815, p = 0.003). As for neuropsychological performance, there were significant main effects for sex and group. Females performed better than males in verbal memory (χ2 = 9.038, p = 0.003) and obtained a higher emotional intelligence quotient (χ2 = 13.20, p < 0.001). On the contrary, males obtained better results in working memory (χ2 = 7.627, p = 0.006). FEP patients significantly underperformed FEM patients in most cognitive domains. There were significant group by sex interactions for few neuropsychological variables, namely processing speed (χ2 = 4.559, p = 0.033) and verbal fluency (χ2 = 8.913, p = 0.003). LimitationsDifferences between sexes were evaluated, but the influence of gender was not considered. Retrospective evaluation of prodromes and substance use. No healthy control group comparator. ConclusionThe main finding is the presence of significant sex effect and group by sex interaction on specific neurocognitive cognition and emotional intelligence measures. Tailored sex-based early treatment strategies might be implemented.

Analysis of the status quo and clinical influencing factors of the social cognitive impairment in deficit schizophrenia.

Due to the high heterogeneity of schizophrenia, the factors influencing social cognitive impairment are controversial. The purpose of this study was to investigate the social cognitive dysfunction of deficit schizophrenia (DS), and to explore its clinical impact on the clinical characteristics and neurocognitive function assessment results. This study involved 100 DS patients, 100 non-deficit schizophrenia (NDS) patients, and 100 healthy controls (HC). Social cognitive functions were assessed using the Eye Complex Emotion Discrimination Task (ECEDT), Game of Dice Task (GDT), and Iowa Gambling Task (IGT), while neurocognitive functions were examined using the Clock Drawing Task (CDT), the Verbal Fluency Task (VFT), Digit Span Test (DST), Stroop Color-word Test (SCWT), and Trail Making Test (TMT). We analyzed the differences in cognitive function among the three groups of patients and the correlation between cognitive function assessment results and Positive and Negative Syndrome Scale (PANSS) scores. Comparison of neurocognitive functions among the three groups through CDT, VFT, DST, SCWT, and TMT revealed that in the values of these tests in the DS group differed significantly from those of the NDS and HC groups. However, the DSB of the NDS group was lower and the TMT results were significantly higher than those of the HC group. In the DS group, ECEDT emotion recognition was positively correlated with stroop colors and stroop interference; the score of gender recognition was positively correlated with VFT, DSF, and SCWT, and TMT-B; the total time spent was positively correlated with TMT; The GDT risky option was negatively correlated with VFT, DST, stroop word, and stroop interference; the negative feedback utilization was negatively correlated with PANSS-Negative; TMT was positively correlated with VFT; IGT was positively correlated with CDT, VFT, DST, and SCWT, but it was negatively correlated with PANSS-Negative and TMT, with statistically significant. There are significant social cognitive impairments in the perception of social information, judgment and resolution of social problems in deficit schizophrenia, which are closely related to negative symptoms and multidimensional neurocognitive dysfunction such as attention, learning, memory, brain information processing speed, cognitive flexibility, and functional executive power.

Exercise as a promoter of neurocognitive improvement in people with psychiatric disorders and comorbid obesity: a randomized controlled trial

IntroductionThe psychiatric disorders and obesity comorbidity is related to neurocognitive impairment and inflammation. Exercise is crucial to improve and maintain healthy lifestyles. This randomized controlled trial tested the efficacy of aerobic exercise as promoter of neurocognitive improvement across psychiatric disorders with comorbid obesity (OB). MethodsPatients with major depressive disorder, bipolar disorder and, schizophrenia and with comorbid OB (n=29) received brief healthy lifestyle counseling and were randomized into two groups: guided physical activity group (GPAG) (n=10) which included 12 weeks of guided-exercise of moderate intensity and frequency, and incentive of autonomous physical activity proposals by the specialist. Standard physical activity group (SPAG) (n=19) continue with their usual daily physical activity, without guidance or incentives, over 12 weeks. Peripheral blood biomarkers of inflammation, oxidative stress, vascular mechanisms, and metabolic activity, as well as neurocognitive and functional performance were assessed twice, before and after intervention. Mixed one-way analysis of variance and linear regression analyses were performed. ResultsIndividuals in GPAG showed better neurocognitive and functional performance than individuals in SPAG after physical activity training (p<0.05; η²p=0.14 to 0.15). A significant improvement in cognition before and after the physical activity training in the GPAG group was found (p<0.0001; η²p=0.29). In all cases, the effect size was from moderate to large. Inflammatory activity (interleukin [IL-6]), oxidative (mitochondrial reactive oxygen species [mROS] and mitochondrial membrane potential [ΔΨm]) and inter cellular adhesion molecule 1 [ICAM1], leukocyte-endothelium adhesion [LEPMN], and p-selectin [PSEL]) levels, and cardio-metabolic (low-density lipoprotein [LDL], systolic blood pressure [SBP], and insulin) processes were significant predicting neurocognitive improve of individuals with psychiatric disorders and comorbid OB. ConclusionsPhysical activity programs may have positive impact on neurocognitive and functional performance in individuals with psychiatric disorders and OB. Exercise influences inflammatory, oxidative, vascular, and cardio-metabolic pathways, and modulate cognition. These findings may have a potential translational utility for early intervention in these disorders.

Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. NCT05168228.