Neurocognitive Research Articles

Age-Related Changes in Brain Structure in Pediatric Chronic Kidney Disease

Pediatric patients with chronic kidney disease (CKD) exhibit reduced cerebellum volume, which is associated with neurocognitive deficits and a lower estimated glomerular filtration rate (eGFR), even before dialysis or transplantation. These differences have not been examined within the context of age-related brain changes during childhood to early adulthood. To evaluate differences in age-related neurodevelopmental changes in patients with CKD compared with control participants and to investigate associations between regional neuroanatomy, functional outcomes, and disease-related variables. Case-control study of individuals aged 6 through 21 years with and without CKD at an academic medical center in Iowa City, Iowa, from September 2016 to August 2024. Neurocognitive testing; 3-T magnetic resonance imaging. Participants completed standardized neurocognitive assessments and quantitative neuroanatomical scans. Brain regions of interest (ROIs) were analyzed for volumetric differences using automated pipelines. Multivariable linear models assessed neurocognitive and neuroanatomical differences between groups, including an age × group interaction for ROI analyses. The sample included 124 individuals (mean [SD] age, 12.8 [4.5] years; 74 [59.7%] male), including 87 control participants (44 [50.6%] male) and 37 participants with CKD (30 [81.1%] male). The mean (SD) eGFR was 71.3 [25.5] mL/min/1.73 m2 for the CKD group. Participants with CKD scored lower than control participants on most neurocognitive measures included in the analyses. The CKD group showed differential age-related changes in cerebellar gray matter (β = -0.10; 95% CI, -0.18 to -0.01; Cohen f = 0.22) and white matter (β = -0.09; 95% CI, -0.19 to -0.00; Cohen f = 0.19). The age × group interaction approached but did not reach significance for amygdala volume (β = 0.09; 95% CI, -0.01 to 0.19; Cohen f = 0.18; P = .06). Volumetric variation in these regions was associated with proxy ratings of executive function in patients with CKD. A significant, positive association between cerebellar gray matter and eGFR was observed in the CKD group (β = 0.04; 95% CI, 0.00 to 0.02; P = .01). In this case-control study, age-related neurodevelopmental differences were observed in pediatric patients with CKD compared with healthy peers. Reductions in cerebellar volume were associated with cognitive deficits and lower kidney function. These findings underscore the importance of monitoring neurodevelopmental trajectories in children with CKD, as early interventions may be necessary to mitigate cognitive impairments associated with CKD.

Brain PET 18-FDG Hypometabolism and Neurocognitive Deficit in Chronic Inhalants Users

Brain PET 18-FDG Hypometabolism and Neurocognitive Deficit in Chronic Inhalants Users

P-905. Post One-year Outcomes for Corticosteroid Use in Non-HIV Cryptococcal Meningoencephalitis

Abstract Background Cryptococcal meningoencephalitis (CM) is a major cause of mortality in HIV/AIDS, transplant recipients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) has been noted to have a favorable response to corticosteroids although long-term responses have not been studied. Methods In addition to standard antifungal therapy, 15 patients admitted with CM/PIIRS from 2015-2020 were treated with standard pulse – taper corticosteroid therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/d, tapered based on clinical and radiological response. One patient was excluded from the study due to death from an unrelated cause within 6 months of diagnosis. Comprehensive neurocognitive testing and MRI brain scans were performed one year after diagnosis to assess clinical status. Results 80% of patients were male, median age 51 years. Median time from antifungal treatment to steroid initiation was 6 weeks. Eleven of 14 patients were neuropsychologically evaluated using performance-based neurocognitive tests. A one-sample T- test showed that the cohort obtained significantly lower scores in memory, learning, language, and information processing/psychomotor speed test in comparison to a normative sample. Also, the mean memory, learning, psychomotor, and information processing speed scores were in the low average range. These findings suggest very mild cognitive deficits in this cohort one year post diagnosis. With the exception of one patient whose MRI brain showed worsened findings at the one-year mark due to a neuro-inflammatory flare, radiological findings suggested stability or improvement for the remaining 13 patients. CSF cultures remained negative. Conclusion Neurocognitive testing performed in a small cohort of previously healthy patients with CM-PIIRS showed an absence of moderate or major neurocognitive deficits one year post diagnosis with minimal adverse effects and no reoccurrence of infection. Brain MRI findings were also stable or improved for the majority. Disclosures All Authors: No reported disclosures

The Impact of Mercury from Dental Amalgams on Pregnancy and Childhood: A Health and Risk Assessment Evaluation.

Mercury is a pervasive global pollutant, with primary anthropogenic sources including mining, industrial processes, and mercury-containing products such as dental amalgams. These sources release mercury into the environment, where it accumulates in ecosystems and enters the food chain, notably through bioamplification in marine life, posing a risk to human health. Dental amalgams, widely used for over a century, serve as a significant endogenous source of inorganic mercury. Studies have demonstrated that mercury vapor can be released from amalgams at room temperature due to material corrosion, potentially leading to chronic exposure. Pregnant women and children are particularly susceptible to mercury's toxic effects, with research linking prenatal mercury exposure to developmental delays, neurocognitive deficits, and conditions such as autism spectrum disorder. Moreover, the long-term accumulation of mercury in the body raises concerns about delayed health impacts in individuals exposed during childhood. Recent findings suggest even low levels of mercury exposure may contribute to kidney damage mediated by oxidative stress, highlighting the importance of monitoring mercury levels in vulnerable populations. Prenatal mercury transfer and postnatal exposure through breastfeeding further amplify the risks. This review critically assesses the health implications of mercury exposure from dental amalgams, focusing on its impact on pregnancy and childhood development. It underscores the need for updated regulatory measures to mitigate mercury-related risks and calls for further research to clarify the extent of mercury's long-term effects on human health.

Multicenter Prospective Pilot Study Identifying Thrombomodulin as a Potential Biomarker for Neurocognitive Outcomes in Immune Thrombotic Thrombocytopenic Purpura

Background/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, chronically relapsing disorder that causes life-threatening thrombotic microangiopathy. Many survivors in clinical remission show evidence of ongoing silent cerebral infarction and neurocognitive deficits. Prospective longitudinal studies of this population are needed to acquire a complete understanding of the mechanism behind this ongoing neurologic injury. We aimed to assess the feasibility of a multicenter prospective study of neuropsychological and cognitive function in iTTP survivors in remission and examine novel biomarkers. Methods: We aimed to enroll 50 iTTP patients across three USTMA consortium sites between 2019 and 2022 in a 24-month longitudinal study. Clinical, cognitive, and biomarker assessments, including ADAMTS13 activity, were performed. Results: Despite the COVID-19 pandemic, we enrolled 38 subjects, and 31 (81.6%) completed closeout evaluations at 24 months. Upon the participants’ enrollment in the study, we confirmed previous findings, including high rates of moderate to severe neurocognitive and psychiatric sequelae (anxiety, 47%; depression, 45%; and headaches, 55%). Changes in cognitive function were measurable and included decreased immediate memory and visuospatial abilities. Over this two-year study, we did not see a significant change in neurocognitive findings. There was no association between cognitive function and ADAMTS13 activity; however, we found that the level of soluble thrombomodulin (CD141) was significantly correlated with cognitive impairment. Conclusions: We conclude that a more extensive study is feasible, and at least 5–10 years may be required to detect trends in neurocognitive function. Soluble thrombomodulin is a promising biomarker for cognitive impairment in survivors of iTTP, and it is worthy of additional study.

Under-recognised neurocognitive deficits in adults and adolescents with tuberous sclerosis complex

BackgroundTuberous sclerosis complex (TSC) is a genetic disease characterised by the growth of benign tumours. The Tuberous sclerosis Associated Neuropsychiatric Disorders (TAND) Checklist is used to identify patient-reported neurocognitive deficits....

Alterations in the inflammatory homeostasis of aging-related cardiac dysfunction and Alzheimer's diseases.

Alzheimer's disease (AD) is well known among the elderly and has a profound impact on both patients and their families. Increasing research indicates that ADis a systemic disease, with a strong connection to cardiovascular disease. They share common genetic factors, such as mutations in the presenilin (PS1 and PS2) and the apolipoprotein E (APOE) genes. Cardiovascular conditions can lead to reduced cerebral blood flow and increased oxidative stress. These factors contribute to the accumulation of Aβ plaques and the formation of abnormal tau protein tangles, which are both key pathological features of AD. Additionally, Aβ deposits and abnormal protein responses have been observed in cardiomyocytes as well as in peripheral tissues. The toxic Aβ deposition intensifies damage to the microvascular structure associated with blood-brain barrier disruption and the initiation of neuroinflammation, which may accelerate the onset of neurocognitive deficits and cardiovascular dysfunction. Thus, we discuss the main mechanisms linking AD and cardiac dysfunction to enhance our understanding of these conditions. Ultimately, insights into the brain-heart axis may help us develop effective treatment strategies in the future.

Hepcidin modifies the relationship between anemia, erythrocyte indices, and neurocognitive performance in virally suppressed people with HIV

Objective: Neurocognitive (NC) impairment in people with HIV (PWH) is associated with erythrocyte indices, which may serve as indicators of iron metabolism, inflammation, and related factors. Erythropoiesis requires iron, regulated by a multifaceted system of peptide hormones, including hepcidin. This study postulated that hepcidin might modify the relationship between erythrocyte indices and NC performance in PWH. Methods: Plasma hepcidin and erythrocyte indices were quantified in 88 virally-suppressed PWH who underwent comprehensive NC assessments. Global NC performance was summarized by global T-scores. Associations of global T-scores with anemia and erythrocyte indices were determined in univariable analyses. To examine the influence of hepcidin on the relationship between NC performance and erythrocyte indices, we evaluated interactions between these covariates in relation to global T-scores and then performed stratified analyses. Results: In multivariable analyses, hepcidin detectability interacted with age (p = 0.007) and mean corpuscular volume (MCV) (p = 0.031) in relation to the global T-score. Interactions between anemia and erythrocyte indices on global T-scores were significant (anemia x MCV, p = 0.008; anemia x MCH, p = 0.011). Stratified analyses identified that lower global T-scores were associated with older age (p = 0.001) and higher MCV (p = 0.0046) and mean corpuscular hemoglobin (MCH, p = 0.026) only when hepcidin was undetectable. Among the anemic, worse global T-score was associated with higher MCV (p = 0.001) and MCH (p = 0.002). Conclusion: Findings suggest that iron-related factors (hepcidin, anemia, MCV, MCH) and age influence neurocognitive health. This cross-sectional study underscores hepcidin as an effect modifier in the associations of erythrocyte indices, anemia, and age with neurocognitive function in PWH.

Anxiety symptoms are distinctly related to working memory deficits in adults with ADHD.

Working memory (WM), the cognitive system that briefly stores and updates information during complex tasks, is one of the most consistently identified neurocognitive deficits in individuals with ADHD. WM deficits are linked to significant challenges in daily life. Adults with ADHD often experience co-occurring anxiety and mood disorders, which are associated with more severe clinical presentations and greater WM deficits. Disentangling how co-occurring depression and anxiety symptoms uniquely contribute to WM deficits in individuals with ADHD is critical for tailoring effective, evidence-based interventions and treatments. This study used a regression approach to explore the relationships among anxiety, depression symptoms, and WM performance in adults with ADHD (n = 439) referred for neuropsychological evaluation at a Midwestern academic medical center. ADHD diagnostic group (ADHD-I and ADHD-C; Predominately Inattentive presentation, and Combined presentation, respectively), depression symptoms, and anxiety symptoms were modeled as predictors of WM performance, with education as a covariate, as education is linked to better cognitive performance. Anxiety and education significantly predicted WM performance, while depression did not, highlighting distinct effects. Anxiety was associated with poorer WM performance, whereas education was linked to better WM. These results emphasize the need for clinical assessments that account for the impacts of specific symptoms on WM in adults with ADHD.

Are there distinct subtypes of developmental dyslexia?

The aim of this study was to identify if children with dyslexia can be distinguished into discrete categories based on their domain deficits, indicating various neurocognitive subtypes of developmental dyslexia (DD). The sample included 101 students in the 3rd, 4th, 5th, and 6th grades of primary school (mean age 11.15 years) with a diagnosis of dyslexia from a public center and Greek as their native language. The students underwent tests assessing a wide range of abilities, specifically phonological, memory, attention, processing speed abilities, motor, visual, and visual-motor skills. Cluster analysis revealed that children with dyslexia can be divided into three subtypes. The first subtype includes children identified based on their performance in tasks evaluating the phonological abilities, memory, attention, processing speed, along with visual-motor and visual skills. The second subtype comprises children identified based on their performance in memory abilities, motor, and visual-motor skills. The third subtype includes children identified solely based on their performance in the motor skills domain. In conclusion, our findings suggest that school-aged children with DD can be categorized into different subtypes with distinct neurocognitive characteristics. Furthermore, the results indicate that most children with dyslexia experience difficulties in more than one cognitive, sensory or motor domains, supporting contemporary models regarding the existence of multiple neurocognitive deficits in DD.

Positive Clinical, Neuropsychological, and Metabolic Impact of Liver Transplantation in Patients With Argininosuccinate Lyase Deficiency.

Liver transplantation (LTx) is increasingly used in Urea Cycle Defects (UCDs) to prevent recurrent hyperammonemia and related neurological irreversible injury. Among UCDs, argininosuccinate lyase deficiency (ASLD) has a more complex phenotype than other UCDs, with long-term neurocognitive deficits. Therefore, the role of LTx in ASLD is still debated. The impact of LTx on nine patients with early-onset ASLD was assessed through pre- and post-LTx clinical, neuropsychological, MRI and biochemical evaluations. After LTx, no episodes of metabolic decompensations were reported. Neuropsychological evaluations documented significant improvement in cognitive/developmental functioning especially in patients transplanted in early childhood. Improvements were also highlighted in daily living skills and emotional-behavioral problems, with a reduction in attention disturbances and somatic complaints. Movement disorders resolved after LTx in patient transplanted in early childhood. Any patients developed epilepsy with stability of EEG alterations after LTx. A positive effect of LTx on other disease-related outcomes such as growth, diet, medications, hospitalizations, and long-term ASLD-related complications was highlighted. The primary biomarker argininosuccinic acid dramatically reduced in plasma after transplantation with a decreasing trend in CSF at long-term follow-up. Moreover, health-related quality of life improved after LTx, especially when assessed through MetabQoL, a tool designed for intoxication diseases such as ASLD. In conclusion, our study showed a global beneficial impact of LTx in early-onset ASLD patients to avoid episodes of hyperammonemia, and improve neurocognitive outcome, adaptive and behavioral deficits when performed in early childhood with a dramatic benefit in terms of quality of life.

The Relationship Between Subjective Cognitive Complaints, Invalid Symptom Reporting, and Neurocognitive Test Performance Validity Among Adults Being Evaluated for ADHD.

Subjective cognitive complaints are common among patients presenting for evaluation of attention-deficit/hyperactivity disorder (ADHD). Despite these complaints, research overwhelmingly suggests that reported cognitive deficits do not align with objective neurocognitive performance. This study explored the relationship between subjective cognitive complaints, objective neuropsychological functioning, and performance and symptom validity testing in adult patients referred for evaluation due to concern about ADHD. The sample consisted of 523 adult referrals who underwent comprehensive evaluation for concern about ADHD and to characterize cognitive strengths and weaknesses. Four hundred patients were diagnosed with ADHD, and 123 did not meet the diagnostic criteria for ADHD. Patients were dichotomized to form nonelevated (n=134) and elevated (n=389) cognitive complaint groups, which were compared on objective neurocognitive performance, report of ADHD-specific symptoms, and performance validity tests. Significant differences were identified between the elevated and nonelevated cognitive complaints groups in performance validity tests and ADHD symptom reporting; however, clinical differences were not identified on objective neurocognitive measures. Consistent with the results of previously published research, subjective cognitive complaints did not align with objective neurocognitive deficits in a sample of adult ADHD referrals. Elevated cognitive complaints were associated with higher rates of performance validity failure and invalid ADHD-specific symptom reporting. These findings highlight the importance of assessing cognitive complaints using symptom report inventories and cognitive tests that include objective validity indices.

Neurocognitive Deficits in Individuals at Ultra-High-Risk for Psychosis: An Overview of Systematic Reviews

Objective: Identifying individuals at ultra-high risk for psychosis (UHRP) is crucial for early intervention and prevention strategies. Neurocognitive deficits have been increasingly recognized as potential predictors of psychosis onset. This overview aims to consolidate current evidence and elucidate the role of neurocognitive predictors in identifying UHRP individuals. Method: we systematically searched three scientific databases, i.e., PubMed, Scopus, and Google Scholar using predefined keywords related to predictive neurocognitive markers and ultra-high risk psychosis. By following the PRISMA procedure, we included all relevant systematic-reviews and meta-analyses in our data-synthesis. Results: Neurocognitive deficits, including impairments in working memory, attentional control, verbal learning, and executive functions, have been consistently identified as predictors of psychosis conversion in individuals at UHRP. Structural and functional neuroimaging studies have further revealed aberrant brain connectivity, reduced gray matter volume, and altered neural activation patterns in key brain regions to be involved in psychosis. Moreover, the combination of neurocognitive and clinical risk factors has been shown to enhance the accuracy of predicting psychosis onset and inform personalized intervention strategies. Conclusion: Neurocognitive deficits serve as valuable predictors of the risk of psychosis in individuals with UHRP, offering insights into the underlying neurobiological mechanisms and potential targets for early intervention. Future research should focus on refining predictive models, elucidating the neurodevelopmental trajectories, and evaluating the efficacy of targeted interventions in mitigating the psychosis risk.

The effect of eye movement desensitization on neurocognitive functioning compared to retrieval-only in PTSD patients: a randomized controlled trial

BackgroundThere is robust evidence that posttraumatic stress disorder (PTSD) is associated with neurocognitive deficits, such as executive dysfunction or memory dysfunction. Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based treatment for PTSD, in which eye movements (EMs) are performed during traumatic memory retrieval. We examined whether Eye Movement Desensitization (EMD) improves neurocognitive functioning in PTSD patients, in comparison with a retrieval-only control condition without EMs.MethodsAdult patients with PTSD (N = 91) were randomized into EMD (N = 47) or retrieval-only (N = 44). Data were collected at baseline (T0), one-week post-treatment (T1), one-month follow-up (T2), and at three-month follow-up (T3). Outcome measures were the California Verbal Learning Test (CVLT), the Trail Making Test (TMT), and the Digit Span Subtest of the Wechsler Adult Intelligence Scale fourth edition (WAIS-IV). We conducted linear mixed model to analyse the main outcomes.ResultsThere was a main effect of time, indicating improvements for both the EMD and retrieval-only groups in CVLT scores, TMT A, TMT B and Digit Span score of WAIS-IV (Bonferroni-adjusted p’s < 0.001) from T0 to T3. There were no effects of group (p = .64) or group by time on CVLT total trial A (T3; p = .34), delay A (T3; p = .76), TMT A (T3; p = .61), TMT B (T3: p = .58), and Digit Span scores (T3; p = .78) of the WAIS-IV, indicating no significant differences between groups on any of the outcomes.ConclusionComparing EMD and retrieval-only did not show evidence for additive effects of EMs on the treatment of PTSD in terms of improvements in neurocognitive functioning. Thus, treatments based on retrieval of traumatic memories may be used to improve neurocognitive functioning in patients with PTSD.Clinical trial registrationThe trial was registered 19/12/2017 at ClinicalTrials.gov, identifier [ISRCTN55239132].

The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.

Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence. Consequently, there is an urgent need for innovative strategies that delay progression and the use of radiation therapy and chemotherapy. The recent Federal Drug Administration (FDA) approval of vorasidenib, a brain-penetrant small molecule targeting mutant IDH1/2 proteins, heralds a shift in the therapeutic landscape for IDH-mutant gliomas. In this review, we address the role of vorasidenib in the treatment of IDH-mutant gliomas, providing a roadmap for its incorporation into daily practice. We discuss ongoing clinical trials with vorasidenib and other IDH inhibitors, as single-agent or in combination with other therapies, as well as current challenges and future directions.

Are ADHD trajectories shaped by the social environment? A longitudinal study of maternal influences on the preschool origins of delay aversion.

Attention-deficit/hyperactivity disorder (ADHD) is commonly attributed to neuro-cognitive deficits of genetic and/or prenatal/perinatal environmental origins. Sonuga-Barke proposed an alternative formulation, suggesting that ADHD behaviors are functional expressions of delay aversion-a strong motivational disposition to avoid or escape negative affective states evoked by delay. It is hypothesized that the strength of this disposition, though neuro-biologically rooted, is exacerbated by early negative social interactions during waiting-related encounters. This paper reports findings from an initial proof-of-concept study that specifically tests this hypothesis in a nonclinical sample. Preschoolers (n = 112; mean age = 46.2 months) and their parents from London, UK, and Hong Kong participated in a longitudinal study. The Parent-Child Delay Frustration Task (PC-DeFT) and two nonwaiting control tasks were administered at baseline. Children's performance, behavioral and emotional responses, and parents' reactions were observed. Teachers rated children's ADHD behaviors and delay aversion at baseline and follow-up (12-18 months later). At baseline, children's maladaptive performance and parental negative reactions during the PC-DeFT were correlated with each other and with teacher ratings of ADHD and delay aversion. Negative parental reactions during the PC-DeFT at baseline predicted an increase in teacher-rated ADHD behaviors at follow-up, but similar associations were not observed for baseline parental responses in the nonwaiting tasks. The increase in child ADHD symptoms associated with negative parental reactions at baseline was statistically mediated by delay aversion. These longitudinal effects were consistent across the UK and HK samples. The findings provide the first evidence that parent's negative reactions to preschooler's attempts to manage delay are associated with increases in ADHD behaviors overtime, and linked to delay aversion increases. They underscore the potential significance of the early social environment as a contributor to developmental trajectory of ADHD behaviors. Future studies with clinical samples over an extended time-frame using a range of different aversive environments (i.e. difficult tasks to complete) are indicated.

Long-term courses of bipolar disorders

Bipolar disorder (short: BD) is asevere illness with very heterogeneous trajectories. While some of the patients show no or hardly any long-term impairments, other affected individuals show substantial neurocognitive deficits with aclear decline in psychosocial functioning. Which factors influence the course of the disease is the subject of current research efforts. This review presents the long-term course of bipolar disease and the factors influencing it. In particular, differential trajectory types are discussed. The cognitive and psychosocial functional level as well as the psychopathological characteristics of the disease are elucidated. In addition, biological factors and treatment approaches influencing the course and prognosis are identified. Literature search using PubMed focusing on longitudinal studies over several years (see online supplement). To date, there are only a few predictors and biomarkers that allow prediction of long-term progression. None have been sufficiently studied to enable clinical use. Appropriate pharmacological and psychotherapeutic treatment of those affected is essential to avoid renewed episodes of the disease. The long-term course of bipolar disorder is highly heterogeneous and multifaceted. Despite intensive research efforts, no predictors have yet been identified that reliably predict the clinical course. This makes further research all the more important in order to offer individualized therapy options, develop new therapies and positively influence the course of the disease at an early stage.

Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries.

Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet. While NTBC modulates the disease course in HT1 patients, several issues are open. Optimal dosage, doses per day, therapeutic range of NTBC concentration, mode of protein restriction and biomarkers are not well defined. HCC and neurocognitive deficits are long-term sequelae. Early diagnosis and treatment are essential to minimise the risk for these complications. Clinical guidance for management of HT1-patients is required. Randomised clinical studies are difficult in the presence of therapeutic options. We discussed these issues in a consensus group of 10 paediatricians, 1 adult hepatologist, 1 geneticist, 2 dieticians, 2 newborn screening specialists with experience in HT1, 1 psychologist and 2 representatives of a patient group from the German-speaking countries (DACH). Recommendations were based on scientific literature and expert opinion, also taking into account recent experience with newborn screening. There was strong consensus that newborn screening using succinylacetone (SA) and early treatment are essential for a good outcome. The dose of NTBC should be as low as possible without losing metabolic control. This has to be accompanied by a low protein diet, in some patients a simplified diet without calculation of protein intake. Specific education and psychosocial support are recommended. Indications for liver transplantation were defined. Monitoring shall include clinical findings, levels of SA, tyrosine, phenylalanine and NTBC in (dried) blood.

Neuropsychological profile of French adults with early-treated phenylketonuria: a multicenter study.

Adult patients with early-treated phenylketonuria (AwET-PKU) may present some subtle neurocognitive deficits. The aim of the study was to investigate 1) neurocognitive functions in a large group of AwET-PKU 2) the influence of plasma phenylalanine (Phe). Participants: 187 AwET-PKU (classic PKU [cPKU] 81%, mild PKU [mPKU] 14%, and mild persistent hyperphenylalaninemia [MPH] 5%). Cognitive assessments: tests included the Wechsler Adult Intelligence Scale-IV, California Verbal Learning Test-II, Trail Making Test, and verbal fluency tests. Biochemical data: plasma Phe was measured concurrently with cognitive assessments. Episodic memory: cPKU patients had lower performance in immediate recall compared to mPKU patients. There was a negative correlation between Phe levels and immediate recall indices, but no correlation with delayed memory. Processing speed: cPKU patients performed worse than mPKU patients in processing speed tests. Negative correlations were observed between Phe levels and processing speed measures, with more pronounced effects in cPKU patients. Executive functioning: No differences were found between cPKU and mPKU patients on executive functioning tests. No correlation was found between executive function and Phe levels. Working memory: cPKU patients had poorer working memory performance compared to mPKU patients, though no correlation was found between working memory performance and Phe levels. The study reveals neurocognitive deficits in adults with PKU, particularly in episodic memory and processing speed. Higher plasma Phe levels are associated with poorer performance in these areas, especially in cPKU patients. Working memory and executive functioning did not show significant correlations with Phe levels.

Altered neural recruitment during single and dual tasks in athletes with repeat concussion.

Sports-related concussions (SRCs) pose significant challenges to college-aged athletes, eliciting both immediate symptoms and subacute cognitive and motor function impairment. While most symptoms and impairments resolve within weeks, athletes with repeat SRCs may experience heightened risk for prolonged recovery trajectories, future musculoskeletal injuries, and long-term neurocognitive deficits. This study aimed to investigate the impact of repeat SRCs on dual task performance and associated neural recruitment using functional near-infrared spectroscopy (fNIRS). A total of 37 college-aged athletes (ages 18-24) participated in this cross-sectional observational study, 20 with a history of two or more SRCs, and 17 controls that had never sustained an SRC. Participants completed the Neuroimaging-Compatible Dual Task Screen (NC-DTS) while neural recruitment in the frontoparietal attention network and the primary motor and sensory cortices was measured using fNIRS. Athletes with repeat SRCs exhibited comparable single task and dual task performance to control athletes. Neuroimaging results indicated altered neural recruitment patterns in athletes with repeat SRCs during both single and dual tasks. Specifically, athletes with repeat SRCs demonstrated increased prefrontal cortex (PFC) activation during single motor tasks compared to controls (p < 0.001, d = 0.47). Conversely, during dual tasks, these same athletes exhibited reduced PFC activation (p < 0.001, d = 0.29) compared to their single task activation. These findings emphasize that while athletes with repeat SRCs demonstrate typical single and dual task performance, persistent alterations in neural recruitment patterns suggest ongoing neurophysiological changes, possibly indicating compensatory neural strategies and inefficient neural resource allocation, even beyond symptom resolution and medical clearance.