Global Impairment Research Articles

Impact of tramadol and heroin abuse on electroencephalography structure and cognitive functions

BackgroundOpioids, defined as medicines that stimulate opioid receptors, are primarily used in the treatment of moderate to severe pain. They induce central nervous system (CNS) adverse effects. This study aimed to assess the effect of opioids on brain electrical activity, the effect of opioids on cognitive functions, and corroborate whether there was any correlation between changes in brain electrical activity and cognitive functions that may do in opioid addicts.MethodsThis cross-sectional case–control study was performed on 80 cases (divided into two groups 40 cases with tramadol use disorders and 40 cases with heroin use disorders) and 40 age-/sex-matched healthy control. All subjects were subordinated to neuropsychiatric evaluation, assessment of opioid use complaint through history from the case and his relatives, substance monitoring in urine, medicine abuse screening test (DAST), electroencephalography (EEG), and cognitive assessment by Montreal Cognitive Assessment (MOCA).ResultsOpioid dependence convinced global cognitive function impairment, specific cognitive disciplines impairment that included visual-conceptual, visual-motor tracking, visual-constructional skills, language function, attention, memory, and orientation. Additionally, affection of the brain’s electrical activities with significant changes compared with control. Comparison of cognitive impairment substantiated by lower cognitive scores in relation to abnormal EEG changes among studied case groups revealed significant differences.ConclusionsOpioid abusers had a significant impairment of cognitive functions and EEG changes with a significant correlation between changes in brain electrical activity and impairment of cognitive functions.

Intragraft regulatory T cells in the modern era: what can high-dimensional methods tell us about pathways to allograft acceptance?

Replacement of diseased organs with transplanted healthy donor ones remains the best and often only treatment option for end-stage organ disease. Immunosuppressants have decreased the incidence of acute rejection, but long-term survival remains limited. The broad action of current immunosuppressive drugs results in global immune impairment, increasing the risk of cancer and infections. Hence, achievement of allograft tolerance, in which graft function is maintained in the absence of global immunosuppression, has long been the aim of transplant clinicians and scientists. Regulatory T cells (Treg) are a specialized subset of immune cells that control a diverse array of immune responses, can prevent allograft rejection in animals, and have recently been explored in early phase clinical trials as an adoptive cellular therapy in transplant recipients. It has been established that allograft residency by Tregs can promote graft acceptance, but whether intragraft Treg functional diversification and spatial organization contribute to this process is largely unknown. In this review, we will explore what is known regarding the properties of intragraft Tregs during allograft acceptance and rejection. We will summarize recent advances in understanding Treg tissue residency through spatial, transcriptomic and high-dimensional cytometric methods in both animal and human studies. Our discussion will explore properties of intragraft Tregs in mediating operational tolerance to commonly transplanted solid organs. Finally, given recent developments in Treg cellular therapy, we will review emerging knowledge of whether and how these adoptively transferred cells enter allografts in humans. An understanding of the properties of intragraft Tregs will help lay the foundation for future therapies that will promote immune tolerance.

Specific brain imaging alterations underlying autistic traits in children with attention-deficit/hyperactivity disorder

BackgroundAutistic traits (ATs) are frequently reported in children with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to examine ATs in children with ADHD from both behavioral and neuroimaging perspectives.MethodsWe used the Autism Spectrum Screening Questionnaire (ASSQ) to assess and define subjects with and without ATs. For behavioral analyses, 67 children with ADHD and ATs (ADHD + ATs), 105 children with ADHD but without ATs (ADHD − ATs), and 44 typically developing healthy controls without ATs (HC − ATs) were recruited. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the mean amplitude of low-frequency fluctuation (mALFF) values (an approach used to depict different spontaneous brain activities) in a sub-sample. The imaging features that were shared between ATs and ADHD symptoms or that were unique to one or the other set of symptoms were illustrated as a way to explore the “brain–behavior” relationship.ResultsCompared to ADHD-ATs, the ADHD + ATs group showed more global impairment in all aspects of autistic symptoms and higher hyperactivity/impulsivity (HI). Partial-correlation analysis indicated that HI was significantly positively correlated with all aspects of ATs in ADHD. Imaging analyses indicated that mALFF values in the left middle occipital gyrus (MOG), left parietal lobe (PL)/precuneus, and left middle temporal gyrus (MTG) might be specifically related to ADHD, while those in the right MTG might be more closely associated with ATs. Furthermore, altered mALFF in the right PL/precuneus correlated with both ADHD and ATs, albeit in diverse directions.ConclusionsThe co-occurrence of ATs in children with ADHD manifested as different behavioral characteristics and specific brain functional alterations. Assessing ATs in children with ADHD could help us understand the heterogeneity of ADHD, further explore its pathogenesis, and promote clinical interventions.

Neuronal models of TDP-43 proteinopathy display reduced axonal translation, increased oxidative stress, and defective exocytosis.

Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disease mostly affecting people around 50-60 years of age. TDP-43, an RNA-binding protein involved in pre-mRNA splicing and controlling mRNA stability and translation, forms neuronal cytoplasmic inclusions in an overwhelming majority of ALS patients, a phenomenon referred to as TDP-43 proteinopathy. These cytoplasmic aggregates disrupt mRNA transport and localization. The axon, like dendrites, is a site of mRNA translation, permitting the local synthesis of selected proteins. This is especially relevant in upper and lower motor neurons, whose axon spans long distances, likely accentuating their susceptibility to ALS-related noxae. In this work we have generated and characterized two cellular models, consisting of virtually pure populations of primary mouse cortical neurons expressing a human TDP-43 fusion protein, wt or carrying an ALS mutation. Both forms facilitate cytoplasmic aggregate formation, unlike the corresponding native proteins, giving rise to bona fide primary culture models of TDP-43 proteinopathy. Neurons expressing TDP-43 fusion proteins exhibit a global impairment in axonal protein synthesis, an increase in oxidative stress, and defects in presynaptic function and electrical activity. These changes correlate with deregulation of axonal levels of polysome-engaged mRNAs playing relevant roles in the same processes. Our data support the emerging notion that deregulation of mRNA metabolism and of axonal mRNA transport may trigger the dying-back neuropathy that initiates motor neuron degeneration in ALS.

Cognitive phenotypes predict response to restorative cognitive rehabilitation in multiple sclerosis

Background: Cognitive phenotyping may be useful for predicting rehabilitation response in multiple sclerosis. Objective: To evaluate the association between cognitive phenotype(s) and response to restorative cognitive rehabilitation (RRCR). Methods: In a post hoc retrospective analysis of the RRCR study including 51 multiple sclerosis patients, we evaluated both impairment within specific cognitive domains as well as overall global impairment severity to investigate their relationship to improvement following rehabilitation. Results: Greater improvement in executive function was predicted by impairment within this domain as well as by having fewer impaired cognitive domains overall. Similar results were observed for visuospatial memory. Conclusions: Patients most likely to benefit from restorative cognitive rehabilitation may exhibit impairment within the domain of interest yet lower cognitive burden overall.

Case report: Neuropsychological assessment in a patient with 4H leukodystrophy

Objective: POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A, POLR3B, POLR1C, or POLR3K genes. Neurological and non-neurological clinical features and disease severity vary. While previous studies reference variable cognition, this is the first report of 4H detailing a comprehensive neuropsychological assessment. Method: The current study presents a 20-year-old, English-speaking, right-handed, non-Hispanic White female with 12 years of education with genetically confirmed 4H POLR3B-related leukodystrophy without hormonal replacement treatment. Results: At age 4, developmental delays, ataxia, hearing loss, and abnormal dentition were present. Imaging, endocrinology, and neurologic examinations revealed hypomyelination, reduced cerebellar volume, delayed bone age density, osteopenia, and evidence of adrenarche without signs of true puberty. Neuropsychological assessment at age 20 revealed global cognitive impairment with intellectual, attention, verbal memory retrieval, construction, executive (e.g. processing speed, sustained attention) and math computation deficits, along with behavioral dysregulation. Conclusion: We present the first detailed neuropsychological assessment of a patient with 4H leukodystrophy. The neuropsychological assessment revealed cognitive and behavioral dysexecutive deficits aligning with hypomyelination observed on imaging. Further longitudinal studies are needed to shed light on the neurobehavioral presentation associated with this disorder to assist care providers, patients, and their families.

Perioperative cognition in association with malnutrition and frailty: a narrative review.

Postoperative delirium (POD) is a prevalent clinical entity characterized by reversible fluctuating altered mental status and cognitive impairment with acute and rapid onset a few days after major surgery. Postoperative cognitive decline (POCD) is a more permanent extension of POD characterized by prolonged global cognitive impairment for several months to years after surgery and anesthesia. Both syndromes have been shown to increase morbidity and mortality in postoperative patients making their multiple risk factors targets for optimization. In particular, nutrition imparts a significant and potentially reversible risk factor. Malnutrition and frailty have been linked as risk factors and predictive indicators for POD and less so for POCD. This review aims to outline the association between nutrition and perioperative cognitive outcomes as well as potential interventions such as prehabilitation.

39 Neurocognitive Function in People Living with HIV from Tijuana: a Comparison Between Norms for Latin-American Population and Norms for US-Mexico Border Region

Objective:Global neurocognitive impairment (NCI) has been reported in white people living with HIV/AIDS (PLWHA) in 40%. In Latino populations there have been variable rates described from 30 to 77%. This variation has to do with the lack of normative data for Latino population and the application of norms for English-speakers, increasing the probability of misidentification of NCI. Thus, recognizing which are the best norms available for the Mexican population is important for the accurate identification of NCI. The aim of the present study was to investigate the rate and pattern of HIV associated neurocognitive impairment (NCI) and to compare rates of NCI between rates calculated using norms for the Latin-American population (NLAP) and norms for the US-Mexico border region (NP-NUMBRS).Participants and Methods:CIOMS international ethical guidelines for the participation of human subjects in health research were followed. 82 PLWHA living in Tijuana (Mexico) participated in the study (Age: Mean=39.6, SD=10.9; 28.3% Female; Years of education: Mean=8.5, SD=3.6). PLWHA were recruited from the board-and-care home “Las Memorias” (73.4% on antiretroviral therapy; Years since HIV diagnosis: Mean=9.9, SD=7.1). Participants completed a neuropsychological test battery sensitive to detect HIV associated NCI that assessed four cognitive domains (verbal fluency, speed of information processing, executive function and learning/memory). Raw scores in these tests were transformed to percentiles using LAPN and transformed to T-scores using NP-NUMBRS. T-scores were averaged across tests to compute domain specific and global impairment scores. NCI was defined as percentile scores <16 and T-scores < 40. McNemar’s tests were used to compare the rate of NCI utilizing NLAP vs NP-NUMBRS.Results:According to NLAP, rates of global NCI were about 13.4%. Utilizing NP-NUMBRS rates of global NCI were about 34.1%. However, there is a positive and significant correlation between Global Neurocognitive Function score in PLWHA according to NLAP and NP-NUMBRS (r=0.66, p<.05). Rates of global NCI in PLWHA were significantly lower when using LAP norms (McNemar Chi-Square=29.89; p<.001). Regarding the pattern of NCI according both norms learning and memory was the most affected cognitive domain with 34% of impairment according to NLAP vs 51% of impairment according to NP-NUMBRs.Conclusions:Utilizing NP-NUMBRS, rates of NCI are consistent with findings of prior studies. Employing norms for LAP the rates of NCI are lower that the ones reported in the literature. This is an important finding since PLWHA included in the sample have several vulnerable factors such as deportation, prostitution, drug abuse and discrimination for sexual preference, factor that could impact cognition. The pattern of neurocognitive function was also similar to those of prior studies in HIV. To accurately make NCI diagnosis it is important to use norms that consider specific characteristics of the population. The diagnosis of NCI is important since these deficits present a strong risk of concurrent problems in a wide range of health behaviors like medication non-adherence in PLWHA.

Allan-Herndon-Dudley syndrome in Hong Kong: Implication for newborn screening

BackgroundAllan-Herndon-Dudley syndrome (MCT 8 deficiency) is an X-linked recessive condition caused by hemizygous pathogenic variants in SLC16A2 encoding the monocarboxylate transporter 8 (MCT8). Patients present with global developmental delay and neurological impairment, and abnormal serum thyroid function tests. The drug, 3,3′,5 triiodothyroacetic acid (TRIAC), was recently demonstrated to improve the endocrinological profile. Improvement in diagnostic approach is key to earlier start of treatment. Patient findingsWe described four Chinese patients with MCT8 deficiency undergoing different diagnostic odysseys. Their initial presentation included global developmental delay and dystonia. Patient 2 also had epilepsy. Patients 1 and 2 presented with two novel variants: (1)hemizygous NM_006517.4(SLC16A2):c.1170 + 2 T > A; p.(?), and (2)hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17) respectively. Patients 3 and 4 were biological brothers harboring hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17), which was first reported in 2004. We obtained the measurement of triiodothyronine (T3) and reverse T3 (rT3) from dried blood spot samples collected on Day 1 of life from Patient 1 and studied the biomarkers (rT3 and T3/rT3 ratio) proposed by Iwayama et al. for the detection of MCT8 deficiency at birth. Our data verified the significantly reduced rT3 level in Patient 1, compared with healthy newborns, although low T3 level and comparable T3/rT3 ratio with controls were detected. SummaryPatients with MCT8 deficiency often undergo diagnostic odysseys. An early diagnosis could be missed by a normal newborn thyroid function screening result based on biochemical measurement of TSH and/or T4/fT4. Early detection of rT3 is key to improving current diagnostic approach. ConclusionWe recommend that full thyroid function profile (TSH, T4/fT4, T3/fT3, rT3) be considered early for all pediatric patients presenting with unexplained developmental delay and/or dystonia. The potential inclusion of rT3 measurement in newborn screening may prove promising.

41 Examining the independent and additive effects of family history of dementia and apolipoprotein e4 on neurocognitive performance among people with HIV

Objective:Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.Participants and Methods:283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.Results:Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).Conclusions:PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

Comorbidity between reading disability and ADHD in a community sample: Implications for academic, social, and neuropsychological functioning.

To better understand the implications of comorbidity between reading disability (RD) and attention-deficit / hyperactivity disorder (ADHD), a sample of 225 participants with RD without ADHD, 139 participants with both RD and ADHD, and 1,502 children without reading or attentional difficulties was recruited through five large public school districts. In comparison to the group without RD or ADHD, both groups with RD exhibited elevations of comorbid internalizing and externalizing disorders and significant global, academic, and social impairment. However, the group with both RD and ADHD was most impaired on most measures, and analyses of neuropsychological measures indicate that the co-occurrence of RD and ADHD may be due at least in part to weaknesses in cognitive processing speed and working memory that are most severe in the comorbid group. These results indicate that psychoeducational assessments of RD should always screen for ADHD and other emotional and behavioral difficulties, and that when RD and ADHD co-occur interventions are likely to be needed for both disorders.

Cognitive, behavioral, neuroimaging and inflammatory biomarkers after hospitalization for COVID-19 in Brazil

Post-COVID-19 Condition (PCC) refers to a multisystemic syndrome that persists for months after SARS-CoV-2 infection. Cognitive deficits, fatigue, depression, and anxiety are common manifestations of the condition, but the underlying mechanisms driving these long-lasting neuropsychiatric features are still unclear. We conducted a prospective multi-method investigation of post-hospitalization COVID-19 patients in Rio de Janeiro, Brazil. Months after hospital admission (mean = 168.45 ± 90.31 days; range = 75.00–365.00 days), COVID-19 survivors (n = 72) presented significant difficulties in tests tapping global cognition, episodic memory, working memory and inhibitory control relative to controls and to validated normative scores. A considerable proportion of participants suffered from fatigue (36.1 %), anxiety (27.8 %), and depressive symptoms (43.1 %). Elevated blood levels of TNF-α, during hospitalization, and TNF-α and IL-1β, at follow-up, correlated with changes in brain microstructural diffusion indices (β = 0.144, p = 0.005). These neuroimaging markers were associated with decreased episodic memory (β = -0.221, p = 0.027), working memory (β = -0.209, p = 0.034) and inhibitory control (β = -0.183, p = 0.010) at follow-up. Severity of depressive symptoms correlated with deficits in global cognition in post-COVID-19 cases (β = -0.366, p = 0.038). Our study provides preliminary evidence that long-term cognitive dysfunction following COVID-19 may be mediated by brain microstructural damage, triggered by persistent neuroinflammation. In addition, depressive symptoms may contribute to prolongated global cognitive impairments in those cases.

Exploring Cognitive Functioning among Forensic Mental Health Inpatients

A large proportion of forensic mental health (FMH) inpatients experience cognitive impairments, which may impact the extent to which they benefit from interventions aimed at reducing their risk of recidivism. These impairments should be identified and responded to as quickly and accurately as possible. The current study explored when and how FMH inpatients’ cognition is assessed during their stay at a forensic hospital, with a cognitive profile being constructed of the sample. The medical files of inpatients who resided at the hospital in Melbourne (Australia) during January 2016 and December 2019 were reviewed retrospectively. A total of 99 medical files were identified. The type, timing and results of each cognitive assessment were collected. Frequency analysis revealed more than half of the sample received a cognitive assessment, with most of the cognitive assessments being conducted within the first year of an inpatient’s admission to hospital. Between 19% and 31% of inpatients with available cognitive data demonstrated a global cognitive impairment, depending on the cognitive measure being used. These results highlight the value of assessing FMH inpatients for cognitive impairments to respond to them appropriately to increase their chances of rehabilitation. Careful consideration should be given to the type of cognitive assessment tool used among this demographic.

Left and right corticobasal syndrome: comparison of cognitive profiles between metabolic imaging - matched groups

BackgroundCorticobasal syndrome (CBS) is typically asymmetric. Case reports suggest that left-hemisphere CBS (lhCBS) is associated with major language impairment, and right-hemisphere CBS (rhCBS) is associated with major visuospatial deficits, but no group study has ever verified these observations. In our study, we enrolled 49 patients with CBS, classified them as lhCBS or rhCBS based on asymmetry of hypometabolism on brain FDG-PET and compared their cognitive and behavioural profiles.MethodsWe defined asymmetry of hypometabolism upon visual inspection of qualitative PET images and confirmed it through paired comparison of left- and right-hemisphere FDG uptake values. The two groups were also matched for severity of hypometabolism within the more affected and more preserved hemispheres, to unravel differences in the cognitive profiles ascribable specifically to each hemisphere’s functional specializations. All patients were assessed for memory, language, executive and visuospatial deficits, apraxia, neglect, dyscalculia, agraphia and behavioural disturbances.ResultsLhCBS (n. 26) and rhCBS (n. 23) patients did not differ for demographics, disease duration and severity of global cognitive impairment. The two cognitive profiles were largely overlapping, with two exceptions: Digit span forward was poorer in lhCBS, and visual neglect was more frequent in rhCBS.ConclusionsAfter balancing out patients for hemispheric hypometabolism, we did not confirm worse language or visuospatial deficits in, respectively, lhCBS and rhCBS. However, verbal short-term memory was more impaired in lhCBS, and spatial attention was more impaired in rhCBS. Both of these functions reflect the functional specialization of the left and right fronto-parietal pathways, i.e. of the main loci of neurodegeneration in CBS.

Associations between mindfulness and mental health after collective trauma: results from a longitudinal, representative, probability-based survey

ABSTRACT Background/objectives Trait mindfulness (TM) may protect against post-trauma mental health ailments and related impairment. Few studies have evaluated this association in the context of collective traumas using representative samples or longitudinal designs. Design/method We explored relationships between TM and collective trauma-related outcomes in a prospective, representative, probability-based sample of 1846 U.S. Gulf Coast residents repeatedly exposed to catastrophic hurricanes, assessed twice during the COVID-19 outbreak (Wave 1: 5/14/20–5/27/20; Wave 2: 12/21/21–1/11/22). Generalized estimating equations examined longitudinal relationships between TM, COVID-19-related fear/worry, hurricane-related fear/worry, global distress, and functional impairment; ordinary least squares regression analyses examined the cross-sectional association between TM and COVID-19-related posttraumatic stress symptoms (PTSS) at Wave 1. Event-related stressor exposure was explored as a moderator. Results In covariate-adjusted models including pre-event mental health ailments and demographics, TM was negatively associated with COVID-19-related fear/worry, hurricane-related fear/worry, global distress, and functional impairment over time; in cross-sectional analyses, TM was negatively associated with COVID-19-related PTSS. TM moderated the relationship between COVID-19 secondary stressor exposure (e.g., lost job/wages) and both global distress and functional impairment over time. Conclusions Results suggest TM may buffer adverse psychosocial outcomes following collective trauma, with some evidence TM may protect against negative effects of secondary stressor exposure.

Domain-specific cognitive impairment 6 months after stroke: The value of early cognitive screening.

Cognitive screening following stroke is widely recommended, yet few studies have considered the prognostic value of acute domain-specific function for longer-term cognitive outcome. Identifying which post-stroke cognitive impairments more commonly occur, recover, and persist, and which impairments hold prognostic value, could inform care planning, and resource allocation. This study aimed to determine the prevalence of domain-specific impairment acutely and at 6 months, assess the proportion of change in cognitive performance, and examine the prognostic value of acute domain-specific cognitive screening. A prospective stroke cohort completed the Oxford Cognitive Screen acutely (⩽2 weeks) and 6 months post-stroke. We determined the prevalence of acute and 6-month domain-specific impairment and proportion of change in performance from acute to 6 months. Hierarchical multivariable regression was used to predict global and domain-specific cognitive impairment at 6 months adjusted for demographic/vascular factors, stroke severity, and lesion volume. A total of 430 stroke survivors (mean/SD age 73.9/12.5 years, 46.5% female, median/interquartile range (IQR) National Institute of Health Stroke Scale (NIHSS) 5/2-10) completed 6-month follow-up. Acutely, domain-specific impairments were highly prevalent ranging from 26.7% (n = 112) in praxis to 46.8% (n = 183) in attention. At 6 months, the proportion of domain-specific recovery was highest in praxis (n = 73, 71%) and lowest in language (n = 89, 46%) and memory (n = 82, 48%). Severity of 6-month cognitive impairment was best predicted by the addition of acute cognitive impairment (adj R2 = 0.298, p < 0.0001) over demographic and clinical factors alone (adj R2 = 0.105, p < 0.0001). Acute cognitive function was the strongest predictor of 6-month cognitive performance (p < 0.0001). Acute domain-specific impairments in memory (p < 0.0001), language (p < 0.0001), and praxis (p < 0.0001) significantly predicted overall severity of cognitive impairment at 6 months. Post-stroke cognitive impairment is highly prevalent across all domains acutely, while impairments in language, memory, and attention predominate at 6 months. Early domain-specific screening can provide valuable prognostic information for longer-term cognitive outcomes.

Investigating the link between regional oxygen metabolism and cognitive speed in multiple sclerosis: Implications for fatigue

BackgroundMost multiple sclerosis (MS) patients experience fatigue and cognitive decline but the underlying mechanisms remain unknown. Previous work has shown whole brain resting cerebral metabolic rate of oxygen (CMRO2) is associated with the extent of these symptoms. However, it is not known if the association between global CMRO2 and MS-related cognitive speed and fatigue can be localized to specific brain regions. Based upon previous research suggesting prefrontal involvement in MS-related changes in cognitive speed and fatigue, we hypothesized that oxygen metabolic changes within prefrontal cortex (PFC) might form the pathophysiologic basis of cognitive performance and fatigue in MS patients. ObjectiveInvestigate whether PFC ΔCMRO2 is associated with cognitive speed and fatigue in MS. MethodsMS and healthy control (HC) participants were scanned using a dual-­echo fMRI sequence and underwent a hypercapnia calibration experiment that permitted estimation of ΔCMRO2 while performing a scanner version of symbol-digit modalities task, a measure of information processing speed and utilized in the clinic as a reliable sentinel biomarker for global cognitive impairment in MS. Participants then completed the Modified Fatigue Impact Scale (MFIS) to measure fatigue. ResultsMS patients exhibited significant reductions in cognitive performance relative to HCs (p < 0.04). Prefrontal ΔCMRO2 explained significant variability (ΔR2 = 0.11) in cognitive speed, over and above disease and demographic variables, for the MS group only. Prefrontal ΔCMRO2 was not associated with fatigue across groups. ΔCMRO2 in visual and motor areas were not associated with cognitive performance or fatigue for either group. ConclusionPrefrontal oxygen metabolism may be a sensitive measure of MS-related cognitive decline.

CAG repeat expansion in the Huntington's disease gene shapes linear and circular RNAs biogenesis.

Alternative splicing (AS) appears to be altered in Huntington's disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage of Htt CAG knock-in mouse in vitro and in vivo models, we demonstrate a correlation between Htt CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and, in vivo, the striatum prior to overt behavioral phenotypes stages. Remarkably, a significant proportion (36%) of the aberrantly spliced isoforms are not-functional and meant to non-sense mediated decay (NMD). The expanded Htt CAG repeats further reflect on a previously neglected, global impairment of back-splicing, leading to decreased circular RNAs production in neural progenitors. Integrative transcriptomic analyses unveil a network of transcriptionally altered micro-RNAs and RNA-binding proteins (Celf, hnRNPs, Ptbp, Srsf, Upf1, Ythd2) which might influence the AS machinery, primarily in neural cells. We suggest that this unbalanced expression of linear and circular RNAs might alter neural fitness, contributing to HD pathogenesis.

Deep phenotyping of socio-emotional skills in children with typical development, neurodevelopmental disorders, and mental health conditions: Evidence from the PEERS.

Socio-emotional skills, including social competence and social cognition, form the basis for robust relationships and wellbeing. Despite their importance, these skills are poorly defined and measured, particularly in children with developmental vulnerabilities. As a consequence, targets for effective management and treatment remain unclear. We aimed to i) phenotype social competence and social cognition in typically developing children (TDC) and in children with neurodevelopmental or mental health disorders (clinical groups) and ii) establish the relationships between these child-direct measures and parent ratings of social competence and behavior. Using a multi-site, cross-sectional study design, we recruited 513 TDC and 136 children with neurodevelopmental (autism spectrum disorder [ASD], attention deficit hyperactivity disorder [ADHD]) or mental health (Anxiety Disorder [ANX]) diagnoses (age range 5-15 years). We administered the Paediatric Evaluation of Emotions, Relationships and Socialisation (PEERS) to children, and parents completed standardised questionnaires rating children's socio-emotional function. Standardised parent questionnaires revealed a global pattern of everyday socio-emotional impairment that was common to all clinical groups, while PEERS identified disorder-specific socio-cognitive profiles for children with ASD, ADHD and ANX. Compared to TDCs, children with ASD demonstrated global socio-cognitive impairment. Children with ADHD were impulsive, demonstrating difficulties managing speed accuracy trade-offs. Children with ANX exhibited slowed social decision-making, but otherwise intact skills. Standardized parent questionnaires of child socio-emotional function reveal differences between children with typical and atypical development, but do not yield disorder-specific, socio-emotional profiles. In contrast, findings from the PEERS objective assessment suggest that that ASD, ADHD and ANX are associated with distinct socio-cognitive phenotypes, to more accurately guide and target management and treatment of impaired social competence.

A - 78 Characterization of Post-Stroke Cognitive and Mood Impairment within 1-Year Post-Stroke after Hospital Discharge.

To demonstrate the feasibility of cognitive and psychological characterization after stroke during post-discharge neurology visit as part of standard care. From January 1, to April 29, 2023, 33 patients were evaluated using the MoCA and screening tests for aphasia, spatial neglect, depression, and anxiety during their neurology outpatient visit. Neuropsychological measures evaluating attention, processing speed, language, visuospatial, memory, and executive function abilities were also administered. Patients were aged 30-87years (Mage = 64.8, SDage = 14.2). The sample included 37.1% women and was primarily Black/African American (37.1%) and White (54.3%). The average level of education was some college (Medu = 14.7, SDedu = 32.7). Time between stroke and testing ranged from 0-11months (Melapsed = 2.8, SDelapsed = 3.1 and 88.6% of patients experienced ischemic stroke. Over 68% of patients examined demonstrated global cognitive impairment on the MoCA (MMoCA = 21.2, SDMoCA = 5.1). 5.7% of patients met criteria for spatial neglect and 5.7% met criteria for aphasia. A higher percentage demonstrated impairments within visuospatial or language domains (51.4% visuospatial and 34.3% language, respectively. Further, impairments were observed across all other domains assessed, including attention (22.9%), processing speed (31.4%), verbal memory (62.9%), visual memory (54.3%), and executive function (51.4%). Depression and anxiety were present in 42.9% and 37.1% of the sample, respectively. Elapsed time, type of stroke, lateralization of stroke, sex, or mood scores were not associated with lower performance on the MoCA. Cognitive and behavioral deficits following stroke can be identified as part of standard neurologic care that may otherwise have been missed, providing an opportunity to intervene and maximize recovery in stroke patients.