Neurocognitive Symptoms Research Articles

Specific sequelae symptoms of COVID-19 of Omicron variant in comparison with non-COVID-19 patients: a retrospective cohort study in Japan.

The specific long-term sequela of coronavirus disease 2019 (COVID-19), also known as long COVID of the Omicron variant remain unclear, due to a lack of cohort studies that include non-COVID patients with cold-like symptoms. The study was conducted to examine specific sequelae symptoms after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which is considered the Omicron variant, compared with patients who were never-infected. In this retrospective cohort study, we sent questionnaires in November 2022, targeting those who visited our fever outpatient unit of a single institution from July to September 2022. SARS-CoV-2 infection status was determined by SARS-CoV-2 polymerase chain reaction (PCR) test results during the study period collected in electronic medical records. Clinical characteristics at 30 days or more since the date of SARS-CoV-2 PCR test were assessed by the questionnaires. Multiple logistic regression was performed to investigate the independent association between SARS-CoV-2 infection and possible sequelae symptoms. In total, valid responses were received from 4,779 patients (mean age: 41.4 years, standard deviation: 19.8 years old). Among them, 3,326 (69.6%) and 1,453 (30.4%) were SARS-CoV-2 PCR test positive and never-infected, respectively. We found that patients with SARS-CoV-2 infection were more likely to have a loss of taste or smell [odds ratio (OR) 4.55, 95% confidence interval (CI): 1.93, 10.71], hair loss (OR 3.19, 95% CI: 1.67, 6.09), neurocognitive symptoms (OR 1.95, 95% CI: 1.43, 2.65), and respiratory symptoms (OR 1.23, 95% CI: 1.03, 1.47) than never-infected patients. SARS-CoV-2 infection was not associated with common cold symptoms, chronic physical distress, or diarrhea as sequelae symptoms. Further, SARS-CoV-2 vaccination showed protective effects on sequelae of loss of taste or smell and hair loss. Loss of taste or smell, hair loss, neurocognitive symptoms, and respiratory symptoms were found to be specific sequelae of the SARS-CoV-2 Omicron variant. It is important not to miss these symptoms that follow SARS-CoV-2 infection and to recognize and manage the long COVID.

#1336 Serotonin levels in hemodialysis patients with Long COVID-associated cognitive impairment

Abstract Background and Aims Long COVID comprises a broad range of persistent symptoms that emerge after COVID-19 and can last for months or years and have a direct impact on daily life. Cognitive impairment and loss of short-term memory are examples of symptoms associated with long COVID. To date, there are neither generally agreed-upon diagnostic criteria nor effective treatments available. A recent study found an association of serotonin deficiency and long COVID in the general population [1], leading to vagal dysfunction and impaired cognition. In this study, we aimed to evaluate longitudinal serotonin levels in hemodialysis (HD) patients with or without cognitive symptoms associated with long COVID. Method We analyzed routinely collected serum samples (n = 102) from 16 HD patients collected between 60 days before and 60 days after a positive SARS-CoV-2 RT-PCR. Metabolites were extracted using cold methanol and subjected to reverse phase liquid chromatography/mass spectrometry (LC/MS). Serotonin was identified by matching retention time, accurate mass, and fragmentation data against an in-house LC/MS library. Log2 of serotonin signal intensity was used for quantification. The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) was administered shortly after positive RT-PCR test, as well as 1- and 6-months post-COVID. Patients were classified as having cognitive symptoms if they reported short-term memory loss or difficulties with concentration or communication problems as per C19-YRS. Unpaired t-test or Fisher's exact tests were performed to compare characteristics of patients with and without cognitive symptoms. We defined three study periods relative to the date of COVID-19 diagnosis: –60 to –15 days (baseline); –14 to +14 days (acute COVID); and +15 to +60 days (post-COVID). Differences in serotonin signal intensity (log2) between patients with and without cognitive symptoms were evaluated with unpaired t-tests. Linear mixed effects models with random intercepts were constructed to determine changes in serotonin levels over time with the baseline period as the comparator. This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK130067). Results Demographic data are presented in Table 1a. Of the 16 patients, 7 (44%) were classified with cognitive symptoms associated with long COVID. There were no differences in age, sex, race, ethnicity, vintage, diabetes, and hypertension between patients with and without cognitive symptoms. Serotonin levels in patients with vs. without cognitive symptoms did not significantly differ at baseline and during acute COVID (Fig. 1). Of note, in the post-COVID phase, serotonin levels were significantly lower in the group with impaired cognition (p = 0.012) compared to symptoms-free patients (Fig. 1). Within each group, serotonin levels remained unchanged at acute-COVID or post-COVID periods compared to baseline (Table 1b). Conclusion We show that HD patients with impaired cognition have lower serotonin in the post-COVID phase compared to patients without cognitive symptoms. These results corroborate findings in the general population. Further investigation in a larger cohort is warranted to evaluate the potential of serotonin as a target for the prevention or as a marker of neurocognitive symptoms associated with long COVID.

Patient Characteristics, Management, and Outcomes in a Novel Cohort of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) increases the risk of bone loss, debilitating fractures, kidney stones, impaired renal function, and neurocognitive symptoms. Studies describing the natural history of PHPT have been limited to small samples, single institutions, or specific populations. We assessed the natural history of PHPT through a large, diverse national cohort from an electronic health record dataset representing more than 100 million patients. The TriNetX database was queried for adult patients with PHPT. We extracted demographics, comorbidities, and longitudinal biochemistries. Primary outcomes included major osteoporotic fracture (MOF) and chronic kidney disease (CKD). Outcomes were stratified by treatment strategy (surgical parathyroidectomy [PTX] vs nonsurgical) and age. Among 50 958 patients with PHPT, 26.5% were treated surgically at a median of 0.3 years postdiagnosis. At diagnosis, median age was 65 years, 74.0% were female, and median calcium level was 10.9 mg/dL. Black and older patients underwent PTX less frequently than White and younger patients. MOF 10-year incidence was 5.20% (PTX) and 7.91% (nonsurgical), with median 1.7-year delay with PTX compared to nonsurgical. PTX-associated MOF absolute risk reduction was 0.83% (age < 65 years) and 3.33% (age ≥ 65 years). CKD 10-year incidence was 21.2% (PTX) and 33.6% (nonsurgical), with median 1.9-year delay with PTX. PTX-associated CKD absolute risk reduction was 12.2% (age < 65 years) and 9.5% (age ≥ 65 years). We report 1 of the largest, representative, population-based natural histories of PHPT with different management strategies. A minority of patients underwent PTX, especially in older age. Patients managed surgically had lower incidence of fracture and CKD, and older patients experienced differential benefit.

High sensitive detection and validation of neuronal specific autoantibodies in post COVID-19 patients with neurocognitive disorders

Abstract COVID-19 has affected tens of million patients worldwide and a significant portion of COVID-19 patients experience post-COVID syndrome characterized by a variety of persistent, debilitating symptoms including profound neurological symptoms. Studies have demonstrated the association between autoantibodies and the severity of COVID-19. but the role of autoantibodies in post-COVID-19 patients with neurological disorders has not yet well established. We screened the levels of anti-neuronal antibodies in 120 serum and CSF samples from 60 post-COVID-19 patients using an OmicsArray™ antigen panel containing 83 neuronal specific antigens (NSA). We identified 7 anti-NSA antibodies which were significantly elevated in serum of at least 1 post-COVID-19 patient with neurocognitive symptoms, including anti-CASPR2, anti-GAD65, anti-RCVRN, anti-mGluR2, anti-MuSK, anti-CSPG4 and anti-ELAVL2 (HuB). 3 anti-NSA antibodies (anti-MOG, anti-GAD65 and anti-mGluR2) were also detected positive in CSF samples of neurocognitive patients. Pre-incubation of the patient serum samples with the purified antigens inhibited the binding of the antibody with the specific NSA on array, validated the specificity of antigen array results. We further confirmed that anti-MuSK antibody in patient serum was targeting the extracellular domain of the MuSK protein using peptide array. Our results suggest anti-NSA antibodies may play a role in post-COVID neurological syndrom and warrant further study.

Long COVID: plasma levels of neurofilament light chain in mild COVID-19 patients with neurocognitive symptoms

It is well known the potential of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection to induce post-acute sequelae, a condition called Long COVID. This syndrome includes several symptoms, but the central nervous system (CNS) main one is neurocognitive dysfunction. Recently it has been demonstrated the relevance of plasma levels of neurofilament light chain (pNfL), as a biomarker of early involvement of the CNS in COVID-19. The aim of this study was to investigate the relationship between pNfL in patients with post-acute neurocognitive symptoms and the potential of NfL as a prognostic biomarker in these cases. A group of 63 long COVID patients ranging from 18 to 59 years-old were evaluated, submitted to a neurocognitive battery assessment, and subdivided in different groups, according to results. Plasma samples were collected during the long COVID assessment and used for measurement of pNfL with the Single molecule array (SIMOA) assays. Levels of pNfL were significantly higher in long COVID patients with neurocognitive symptoms when compared to HC (p = 0.0031). Long COVID patients with cognitive impairment and fatigue symptoms presented higher pNfL levels when compared to long COVID patients without these symptoms, individually and combined (p = 0.0263, p = 0.0480, and 0.0142, respectively). Correlation analysis showed that levels of cognitive lost and exacerbation of fatigue in the neurocognitive evaluation had a significative correlation with higher pNfL levels (p = 0.0219 and 0.0255, respectively). Previous reports suggested that pNfL levels are related with higher risk of severity and predict lethality of COVID-19. Our findings demonstrate that SARS-CoV-2 infection seems to have a long-term impact on the brain, even in patients who presented mild acute disease. NfL measurements might be useful to identify CNS involvement in long COVID associated with neurocognitive symptoms and to identify who will need continuous monitoring and treatment support.

Neurocognitive Impairment and Social Cognition in Parkinson's Disease Patients.

In addition to motor symptoms, neurocognitive impairment (NCI) affects patients with prodromal Parkinson's disease (PD). NCI in PD ranges from subjective cognitive complaints to dementia. The purpose of this review is to present the available evidence of NCI in PD and highlight the heterogeneity of NCI phenotypes as well as the range of factors that contribute to NCI onset and progression. A review of publications related to NCI in PD up to March 2023 was performed using PubMed/Medline. There is an interconnection between the neurocognitive and motor symptoms of the disease, suggesting a common underlying pathophysiology as well as an interconnection between NCI and non-motor symptoms, such as mood disorders, which may contribute to confounding NCI. Motor and non-motor symptom evaluation could be used prognostically for NCI onset and progression in combination with imaging, laboratory, and genetic data. Additionally, the implications of NCI on the social cognition of afflicted patients warrant its prompt management. The etiology of NCI onset and its progression in PD is multifactorial and its effects are equally grave as the motor effects. This review highlights the importance of the prompt identification of subjective cognitive complaints in PD patients and NCI management.

Self-reported anterograde memory loss in older persons that is not validated on neuropsychological assessment: Considerations for a dissociative diagnosis

The past decade has witnessed amplified public awareness of age-related dementias. This has resulted in a dramatic rise in the number of older persons referred to memory clinics with a primary complaint of self-reported memory loss without an antecedent neurological event (e.g., stroke) who produce neuropsychological test profiles that lack evidence of such impairment. Since the latter part of the 19th century, a confusing array of changing terminology, criteria, and perceived causation have been ascribed to patients with unverified medical symptoms to implicate psychological causation. Such terms are often misperceived by laypersons as reflecting character flaws or malingering. Of import for clinical neuropsychologists, the 11th edition of the International Classification of Diseases added cognitive to symptoms eligible for a diagnosis of the modern formulation, dissociative neurological symptom disorder. One dissociative option for referrals with self-reported neurocognitive symptoms not validated on neuropsychological testing is functional memory disorder, conceived as a psychological disorder where emotional distress is plausibly related to the perceived memory loss but is of less severity than would warrant a major depressive or anxiety diagnosis. If evidence of psychological distress or behavioral impairment is not present the referral likely reflects the increased public awareness of age-related dementias interacting with the high base rate of self-perceived memory loss in the general population. In such cases, a dissociative diagnosis should be avoided as there is evidence of neither a medical nor a psychological disorder. A summary statement of not dementia or similar is likely sufficient to help the patient.

Head Injury Treatment With Healthy and Advanced Dietary Supplements: A Pilot Randomized Controlled Trial of the Tolerability, Safety, and Efficacy of Branched Chain Amino Acids in the Treatment of Concussion in Adolescents and Young Adults.

Concussion is a common injury in the adolescent and young adult populations. Although branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild-to-moderate traumatic brain injury (TBI), to date, no studies have been performed evaluating the efficacy of BCAAs in concussed adolescents and young adults. The goal of this pilot trial was to determine the efficacy, tolerability, and safety of varied doses of oral BCAA supplementation in a group of concussed adolescents and young adults. The study was conducted as a pilot, double-blind, randomized controlled trial of participants ages 11-34 presenting with concussion to outpatient clinics (sports medicine and primary care), urgent care, and emergency departments of a tertiary care pediatric children's hospital and an urban tertiary care adult hospital, between June 24, 2014 and December 5, 2020. Participants were randomized to one of five study arms (placebo and 15 g, 30 g, 45 g, and 54 g BCAA treatment daily) and followed for 21 days after enrollment. Outcome measures included daily computerized neurocognitive tests (processing speed, the a priori primary outcome; and attention, visual learning, and working memory), symptom score, physical and cognitive activity, sleep/wake alterations, treatment compliance, and adverse events. In total, 42 participants were randomized, 38 of whom provided analyzable data. We found no difference in our primary outcome of processing speed between the arms; however, there was a significant reduction in total symptom score (decrease of 4.4 points on a 0-54 scale for every 500 g of study drug consumed, p value for trend = 0.0036, [uncorrected]) and return to physical activity (increase of 0.503 points on a 0-5 scale for every 500 g of study drug consumed, p value for trend = 0.005 [uncorrected]). There were no serious adverse events. Eight of 38 participants reported a mild (not interfering with daily activity) or moderate (limitation of daily activity) adverse event; there were no differences in adverse events by arm, with only two reported mild adverse events (both gastrointestinal) in the highest (45 g and 54 g) BCAA arms. Although limited by slow enrollment, small sample size, and missing data, this study provides the first demonstration of efficacy, as well as safety and tolerability, of BCAAs in concussed adolescents and young adults; specifically, a dose-response effect in reducing concussion symptoms and a return to baseline physical activity in those treated with higher total doses of BCAAs. These findings provide important preliminary data to inform a larger trial of BCAA therapy to expedite concussion recovery.

Who develops long COVID? Longitudinal pre-pandemic predictors of long COVID and symptom clusters in a representative Dutch population

ObjectivesPrior studies show that long COVID has a heterogeneous presentation. Whether specific risk factors are related to subclusters of long COVID remains unknown. This study aimed to determine pre-pandemic predictors of long COVID and symptom clustering. MethodsA total of 3,022 participants of a panel representative of the Dutch population completed an online survey about long COVID symptoms. Data was merged into 2018/2019 panel data covering sociodemographic, medical, and psychosocial predictors. A total of 415 participants were classified as having long COVID. K-means clustering was used to identify patient clusters. Multivariate and lasso regression was used to identify relevant predictors compared to a COVID-19 positive control group. ResultsPredictors of long-term COVID included older age, Western ethnicity, BMI, chronic disease, COVID-19 reinfections, severity, and symptoms, lower self-esteem, and higher positive affect (AUC = 0.79, 95%CI 0.73-0.86). Four clusters were identified: a low and a high symptom severity cluster, a smell-taste and respiratory symptoms cluster, and a neuro-cognitive, psychosocial, and inflammatory symptom cluster. Predictors for the different clusters included regular health complaints, healthcare use, fear of COVID-19, anxiety, depressive symptoms, and neuroticism. ConclusionsA combination of sociodemographic, medical, and psychosocial factors predicted long COVID. Heterogenous symptom clusters suggest that there are different phenotypes of long COVID-19 presentation.

Hyperbaric Oxygen Therapy Improves Neurocognitive Functions and Symptoms of Post-COVID Condition: Randomized Controlled Trial (P7-11.005)

Hyperbaric Oxygen Therapy Improves Neurocognitive Functions and Symptoms of Post-COVID Condition: Randomized Controlled Trial (P7-11.005)

Abstract 7448: Serum IL-10 is associated with neurologic symptoms and interference in primary brain tumor patients

Abstract Background: Primary brain tumors (PBT) are associated with neurocognitive symptoms as a direct result of the tumor or its treatment. IDH-mutant gliomas are associated with longer survival, but with higher incidence of seizures and neurocognitive symptoms.​ Correlations between cytokines and neuroinflammation have been reported in other structural brain lesions but have not been evaluated in PBT. Here, we investigate elevated peripheral blood levels of proteins (cytokine levels) in a cross-sectional cohort (n=47) of adult, IDH-mutant PBT patients enrolled in a natural history study (NCT02851706, PI: T. Armstrong) versus healthy subjects (n=32) and the correlations between cytokine levels and patient-reported outcomes (PROs). Methods: Patient-reported symptoms and activity-related interference were collected via the MD Anderson Symptom Inventory-Brain Tumor at study entry. Serum samples were stored at -80°C for batch processing and used for biomarker analysis. Ten cytokines (interleukin-1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ [IFN-γ], and tumor necrosis factor-α [TNF-α]) were quantified in duplicate using an immunoassay (V-Plex/Proinflammatory, Meso Scale Discovery [MSD], Rockville, MD). Lab personnel were blinded to diagnosis and patient clinical status. Mean concentration (pg/mL) levels or ‘present or not detectable’ values were used. Descriptive statistics, Mann-Whitney tests, and Spearman correlations were conducted at p &amp;lt;0.05. Results: The patient sample was mostly male (62%), White (70%), employed (64%), had no prior recurrence (62%), high grade (3-4) tumors (70%), and an average age at diagnosis of 36 years (SD: 9; median: 34; range: 20-53). The healthy subject sample was mostly female (53%) and White (72%), with an average age of 46 years (SD: 19; median: 50; range: 19-78). Five cytokines (IFN-γ, IL-6, IL-8, IL-10, and TNF-α) were detectable in patients and healthy subjects with levels of IL-6, IL-10, and TNF-α higher in patients than healthy subjects. Serum levels of IL-10 (mean rank=50.7 vs 24.3, p&amp;lt;0.001) and TNF-α (mean rank=50.6 vs 24.2, p&amp;lt;0.001) were higher in PBT patients when compared to healthy subjects. Only IL-10, but not other cytokines, positively correlated with severity of patient-reported symptoms [pain (r=0.290, p=0.048), numbness/tingling (r=0.302, p=0.039)], and activity-related interference, including work (r=0.323, p=0.027), and walking (r=0.402, p=0.005). Conclusions: Higher IL-10 levels and detection differences in other cytokines, may indicate a reduction in immune-mediating processes and heightening inflammation in patients. Future analysis will include replication of this work in a larger cohort across PBT types to evaluate risk, explore mechanisms, and associations with treatment types. Citation Format: Kaitlynn A. Slattery, Michelle L. Wright, Dhaivat Raval, Emory Hsieh, McKenzie C. Kauss, Terri S. Armstrong, Tito R. Mendoza, Vivian A. Guedes. Serum IL-10 is associated with neurologic symptoms and interference in primary brain tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7448.

Molecular basis of neurocognitive dysfunction and psychosis in Alpha-Mannosidosis

A significant portion of patients who are afflicted with lysosomal storage diseases (LSDs) encounter neurological manifestations, including cognitive issues and developmental delay, seizures, psychiatric issues, and an overall neurodegenerative decline. In order to enhance the development of effective therapies for these symptoms, it is imperative that we allude to the neuropathophysiology that underlies these manifestations. These distinct neurological and developmental features are particularly evident in patients with Alpha-Mannosidosis (AM), a type of LSD. However, there is limited published information regarding the mechanisms and pathophysiology of these presentations in patients with this condition. Although the precise impact of lysosomal storage on the biogenesis and functioning of neuronal cells has not been clearly defined, recent studies have placed emphasis on the significance of synaptic defects influencing this dysfunction. These defects encompass changes in synaptic spines, proteins, and vesicles, as well as postsynaptic densities that potentially precipitate functional disruptions in synaptic transmission and neurodegeneration. Ultimately, this cascade is thought to result in extensive neuronal loss and, consequently, the onset of cognitive manifestations. Uncovering the effects on synaptic components in LSDs with neurological symptoms like AM will enable a better understanding of disease progression. It will also allow us to identify critical targets for therapeutic intervention and the determination of optimal time frames for targeted treatments, as well as the effects of these treatments on mitochondrial function. The available therapeutic modalities in AM are not a definitive cure for affected patients, but rather an attempt to reduce the symptomatic severity in their presentation, while aiming to regress/slow down disease progression. This review will aim to discuss and rationalize the current treatment approaches in place for AM patients in relation to their effects on the improvement of neurocognitive symptoms in affected AM individuals.

Factors associated with prolonged COVID-related PTSD-like symptoms among adults diagnosed with mild COVID-19 in Poland.

COVID-19 has been considered a possible cause of post-traumatic stress disorder (PTSD) or similar conditions. However, what specific disease symptoms may contribute most to prolonged PTSD-like symptoms in COVID-19 survivors is unclear. The study aimed to present the factor structure of COVID-19 symptoms and identify which symptoms of COVID-19 best explain the subsequent presence of PTSD-like symptoms in mild COVID-19 survivors. COVID-positive adults (n = 341) completed online self-report scales at the baseline assessment (T1) and after approximately 4 months (T2), including The Patient Health Questionnaire Anxiety-Depression Scale; The Scale of Psychosocial Experience Related to COVID-19, The Primary Care PTSD Screen for DSM-5; and self-designed questionnaires evaluating the severity of COVID-related medical and neurocognitive symptoms and pre-pandemic variables. Exploratory factor analysis revealed five factors of COVID-19 symptoms: flu-like, respiratory, cold, neurological, and neurocognitive. Hierarchical logistic regression showed that besides selected control variables (anxiety and depression, presence of PTSD-like symptoms, COVID-related stigma in T1), neurocognitive symptoms of COVID-19 in T1 but not other symptoms of the disease were a significant predictor of the presence of PTSD-like symptom in T2. Findings suggest a need for a comprehensive neurocognitive assessment of people diagnosed with COVID-19 and prompt interventions targeting the prevention of potential risks for long-term PTSD-like states at the community level.

Do people with ME/CFS and joint hypermobility represent a disease subgroup? An analysis using registry data.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multifaceted disease that affects millions globally. Despite its significant impact, the disease's etiology remains poorly understood, and symptom heterogeneity poses challenges for diagnosis and treatment. Joint hypermobility, commonly seen in hypermobile Ehlers-Danlos Syndrome (hEDS), has been observed in ME/CFS patients but its prevalence and clinical significance within this population are not well-characterized. To compare the characteristics of ME/CFS patients with and without joint hypermobility (JH+ and JH-) as assessed using the Beighton scoring system, and to explore whether JH+ ME/CFS patients exhibit distinct disease characteristics, comorbidities, and health-related quality of life (HRQOL). The study used cross-sectional, self-reported data from 815 participants of the You + ME Registry. Participants were categorized as JH+ or JH- based on self-assessed Beighton scores and compared across demographics, comorbidities, family history, and symptoms. HRQOL was assessed using the Short Form-36 RAND survey and Karnofsky Performance Status. 15.5% (N = 126) of participants were classified as JH+. JH+ participants were more likely to be female, report Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and a family history of EDS. They experienced worse HRQOL, particularly in physical functioning and pain, and a higher number of autonomic, neurocognitive, headache, gut, and musculoskeletal symptoms. Sensitivity analysis suggested that ME/CFS with concurrent JH+ and EDS was associated with more severe symptoms and greater functional impairment. ME/CFS patients with joint hypermobility, particularly those with EDS, demonstrate distinct clinical characteristics, including more severe symptomatology and reduced HRQOL. These findings highlight the need for comprehensive clinical assessments of ME/CFS patients with joint hypermobility. Understanding these relationships could aid in subgroup identification, improving diagnosis, and informing targeted therapeutic approaches. Further research is warranted to explore these associations and their implications for clinical practice.

The relationship between social determinants of health and neurocognitive and mood-related symptoms in the primary brain tumor population: A systematic review.

Social determinants of health (SDOH) impact cancer-related health outcomes, including survival, but their impact on symptoms is less understood among the primary brain tumor (PBT) population. We conducted a systematic review to examine the relationships between SDOH and neurocognitive and mood-related symptoms among the PBT population. PubMed, EMBASE, and CINAHL were searched using PROGRESS criteria (place of residence, race/ethnicity, occupation, gender/sex, religion, education, socioeconomic status, and social capital) on March 8th, 2022. Two individuals screened and assessed study quality using the NHLBI Assessment Tool for Observational Cohort and Cross-sectional Studies. Of 3006 abstracts identified, 150 full-text articles were assessed, and 48 were included for a total sample of 28 454 study participants. Twenty-two studies examined 1 SDOH; none examined all 8. Four studies measured place of residence, 2 race/ethnicity, 13 occupation, 42 gender, 1 religion, 18 education, 4 socioeconomic status, and 15 social capital. Fifteen studies assessed neurocognitive and 37 mood-related symptoms. While higher education was associated with less neurocognitive symptoms, and among individuals with meningioma sustained unemployment after surgery was associated with depressive symptoms, results were otherwise disparate among SDOH and symptoms. Most studies were descriptive or exploratory, lacking comprehensive inclusion of SDOH. Standardizing SDOH collection, reducing bias, and recruiting diverse samples are recommended in future interventions.

Symptom trajectories of post-COVID sequelae in patients with acute Delta or Omicron infection in Bergen, Norway.

A substantial proportion of the over 700 million COVID-19 cases world-wide experience long-term symptoms. The objectives of this study were to compare symptom trajectories and risk factors for post-COVID-19 condition after Delta and Omicron infection. This study consecutively recruited patients with SARS-CoV-2 infection from November 2021 to March 2022. We recorded demographics, comorbidities, vaccination status, sick leave, and 18 symptoms during acute infection and after 4 months. The primary outcome measures were symptoms during acute infection and after 4 months. Secondary outcome measures were work and school absenteeism. We followed a cohort of 1,374 non-hospitalized COVID-19 patients in Bergen, Norway, at three time points. The median age was 39.8 years and 11% were children <16 years. Common acute upper respiratory symptoms waned during follow-up. Fatigue remained common from acute infection (40%) until after 4 months (37%). Four months post-infection, patients reported increased frequencies of dyspnea (from 15% during acute illness to 25% at 4 months, p < 0.001), cognitive symptoms (from 9 to 32%, p < 0.001) and depression (from 1 to 17%, p < 0.001). Patients infected with Omicron reported less dyspnea (22% versus 27%, p = 0.046) and smell/taste problems (5% versus 19%, p < 0.001) at 4 months follow-up than those with Delta infection. Comorbidities and female sex were risk factors for persistent dyspnea and cognitive symptoms. Ten percent reported sick leave after acute illness, and vaccination reduced the risk of absenteeism (adjusted risk ratio: 0.36, 95% confidence interval: 0.15, 0.72, p = 0.008). At 4 months, home-isolated patients infected with Omicron reported overall comparable symptom burden, but less dyspnea and smell/taste problems than Delta infected patients. Several acute symptoms waned during follow-up. It is worrying that dyspnea, neurocognitive symptoms, and particularly depression, increased significantly during the first 4 months after acute infection. Previous vaccination was protective against prolonged sick leave.

Somatic CAG repeat instability in intermediate alleles of the HTT gene and its potential association with a clinical phenotype.

Huntington disease (HD) is a neurodegenerative disorder caused by ≥36 CAGs in the HTT gene. Intermediate alleles (IAs) (27-35 CAGs) are not considered HD-causing, but their potential association with neurocognitive symptoms remains controversial. As HTT somatic CAG expansion influences HD onset, we hypothesised that IAs are somatically unstable, and that somatic CAG expansion may drive phenotypic presentation in some IA carriers. We quantified HTT somatic CAG expansions by MiSeq sequencing in the blood DNA of 164 HD subjects and 191 IA (symptomatic and control) carriers, and in the brain DNA of a symptomatic 33 CAG carrier. We also performed genotype-phenotype analysis. The phenotype of symptomatic IA carriers was characterised by motor (85%), cognitive (27%) and/or behavioural (29%) signs, with a late (58.7 ± 18.6 years), but not CAG-dependent, age at onset. IAs displayed somatic expansion that were CAG and age-dependent in blood DNA, with 0.4% and 0.01% of DNA molecules expanding by CAG and year, respectively. Somatic expansions of +1 and +2 CAGs were detected in the brain of the individual with 33 CAGs, with the highest expansion frequency in the putamen (10.3%) and the lowest in the cerebellum (4.8%). Somatic expansion in blood DNA was not different in symptomatic vs. control IA carriers. In conclusion, we show that HTT IAs are somatically unstable, but we found no association with HD-like phenotypes. It is plausible, however, that some IAs, close to the HD pathological threshold and with a predisposing genetic background, could manifest with neurocognitive symptoms.

Neurological involvement among non-hospitalized adolescents and young adults 6 months after acute COVID-19.

The post-COVID-19 condition (PCC) is characterized by debilitating persistent symptoms, including symptoms suggesting neurological aberrations such as concentration difficulties, impaired memory, pain, and sleep disturbances. The underlying mechanisms remain elusive. This study aimed to investigate brain injury biomarkers, neurocognitive test performance, and self-reported neurological and neuropsychological symptoms in young people with PCC. A total of 404 non-hospitalized adolescents and young adults aged 12-25 years who tested positive for SARS-CoV-2, along with 105 matched SARS-CoV-2 negative individuals, were prospectively enrolled and followed-up for 6 months (Clinical Trials ID: NCT04686734). All participants underwent comprehensive assessment encompassing clinical examinations, questionnaires, neurocognitive testing and blood sampling. Serum samples were immunoassayed for the brain injury biomarkers neurofilament light chain (Nfl) and glial fibrillary acidic protein (GFAp). At 6 months, cross-sectional analyses of serum Nfl/GFAp, neurocognitive test results and symptom scores were performed across groups based on adherence to PCC criteria as well as initial SARS-CoV-2 test results. Also, associations between Nfl/GFAp, neurocognitive test results, and symptom scores were explored. A total of 381 SARS-CoV-2 positive and 85 SARS-CoV-2 negative were included in the final analysis at 6 months, of whom 48% and 47%, respectively, adhered to the PCC criteria. Serum levels of Nfl and GFAp were almost equal across groups and did not differ from reference values in healthy populations. Also, neurocognitive test results were not different across groups, whereas symptom scores were significantly higher in patients fulfilling PCC criteria (independent of initial SARS-CoV-2 status). No significant associations between Nfl/GFAp, neurocognitive test results, and symptom scores were found. Normal brain injury biomarkers and neurocognitive performance 6 months after mild COVID-19 implies that the persistent symptoms associated with PCC are not concurrent with ongoing central nervous system damage or permanent disruption of cognitive functions. This finding contradicts the notion of neuroinflammation as a likely explanation for the persistent symptoms.

Electrode position and cognitive outcome following deep brain stimulation surgery.

Subthalamic nucleus (STN) and globus pallidus internus (GPI) deep brain stimulation (DBS) effectively treat motor symptoms in Parkinson's disease (PD) but may be associated with cognitive and psychiatric changes in some patients. Evaluation of changes in cognitive and psychiatric symptoms following DBS is complicated by changes in these symptoms that occur as part of the natural disease course. The aim of this study was to evaluate whether electrode position was associated with changes in neurocognitive symptoms in patients who underwent STN and GPI DBS. A single-institution retrospective cohort study was conducted on patients with PD who underwent DBS from 2008 to 2019. Cognitive and psychiatric outcomes included Beck Depression Inventory II (BDI-II) score, presence of impulsive-compulsive behavior (ICB), Mini-Mental State Examination (MMSE) score, and overall cognitive status grade determined by comprehensive neuropsychology testing (normal, mild impairment, moderate impairment, and dementia). Pre- and postoperative comparisons were performed using a Wilcoxon signed-rank test or paired t-test. Patients with and without cognitive decline were compared using a Mann-Whitney U-test or unpaired t-test. A chi-square test was used for categorical comparisons. One hundred thirty patients were included (mean age 62.5 ± 7.9 years). At a mean postoperative follow-up from DBS of 13.0 ± 12.7 (range 6-66) months, there was an improvement in ICB (26.3% preoperatively vs 15.0% postoperatively, p = 0.017), but a decline in MMSE score (28.6 ± 1.6 vs 27.6 ± 2.0, p < 0.001) and overall cognitive status (normal: 66.2% vs 39.2%; mild: 12.3% vs 17.7%; moderate: 21.5% vs 33.1%; dementia: 0.0% vs 10.0%; p < 0.001). Patients undergoing STN DBS had a worse decline in overall cognitive status than patients who underwent GPI DBS (p = 0.006). Postoperative cognitive decline was associated with a more medial electrode position only for patients who underwent STN DBS. Cognitive change was observed in some patients with PD who underwent both GPI and STN DBS, likely due partly to underlying disease progression. Compared with GPI DBS, STN DBS was associated with a greater likelihood of cognitive decline. In STN but not GPI DBS, cognitive decline was associated with medialized electrode position, suggesting modulation of nonmotor STN divisions may contribute to cognitive changes following STN DBS.

Characterisation, symptom pattern and symptom clusters from a retrospective cohort of Long COVID patients in primary care in Catalonia

BackgroundAround 10% of people infected by SARS-COV-2 report symptoms that persist longer than 3 months. Little has been reported about sex differences in symptoms and clustering over time of non-hospitalised patients in primary care settings.MethodsThis is a descriptive study of a cohort of mainly non-hospitalized patients with a persistence of symptoms longer than 3 months from the clinical onset in co-creation with the Long Covid Catalan affected group using an online survey. Recruitment was from March 2020 to June 2021. Exclusion criteria were being admitted to an ICU, < 18 years of age and not living in Catalonia. We focused on 117 symptoms gathered in 18 groups and performed cluster analysis over the first 21 days of infection, at 22–60 days, and ≥ 3 months.ResultsWe analysed responses of 905 participants (80.3% women). Median time between symptom onset and the questionnaire response date was 8.7 months. General symptoms (as fatigue) were the most prevalent with no differences by sex, age, or wave although its frequency decreased over time (from 91.8 to 78.3%). Dermatological (52.1% in women, 28.5% in men), olfactory (34.9% women, 20.9% men) and neurocognitive symptoms (70.1% women, 55.8% men) showed the greatest differences by sex. Cluster analysis showed five clusters with a predominance of Taste & smell (24.9%) and Multisystemic clusters (26.5%) at baseline and _Multisystemic (34.59%) and Heterogeneous (24.0%) at ≥3 months. The Multisystemic cluster was more prevalent in men. The Menstrual cluster was the most stable over time, while most transitions occurred from the Heterogeneous cluster to the Multisystemic cluster and from Taste & smell to Heterogeneous.ConclusionsGeneral symptoms were the most prevalent in both sexes at three-time cut-off points. Major sex differences were observed in dermatological, olfactory and neurocognitive symptoms. The increase of the Heterogeneous cluster might suggest an adaptation to symptoms or a non-specific evolution of the condition which can hinder its detection at medical appointments. A carefully symptom collection and patients’ participation in research may generate useful knowledge about Long Covid presentation in primary care settings.