Neurocognitive Impairment Research Articles

The unseen impact - a deep dive into neurocognitive impairment among patients with intracranial meningiomas: a comprehensive systematic review of the literature.

Meningiomas are the most common intracranial tumors, predominantly affecting adults, with a higher incidence in female and elderly populations. Despite their prevalence, research on neurocognitive impairment in meningioma patients remains limited compared to intra-axial tumors such as gliomas. We conducted a comprehensive systematic review of the current literature on neurocognitive outcomes in meningioma patients pre- and post-surgery. Our review revealed significant disparities in reported neurocognitive outcomes, with prospective studies suggesting tumor-related factors as the primary contributors to postoperative deficits, while retrospective studies imply surgical intervention plays a significant role. Regardless of study design or specifics, most studies lack baseline preoperative neurocognitive assessments and standardized protocols for evaluating neurocognitive function. To address these gaps, we advocate for standardized neurocognitive assessment protocols, consensus on neurocognitive domains to be targeted in this population by tailored test batteries, and more prospective studies to elucidate correlations between tumor characteristics, patient attributes, surgical interventions, neurocognitive status, and planning for implementing tailored neurocognitive rehabilitation strategies early in the postoperative course which is crucial for achieving optimal long-term neurocognitive outcomes and enhancing patients' quality of life.

Fisetin-loaded pluronic-based nanogel: Radiation synthesis for alleviating neurocognitive impairments in a rat model of alzheimer's disease via modulation of the apoptotic cascade

Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive impairment and memory loss. In this study, AD was experimentally induced in rats using aluminum chloride (AlCl3) and D-galactose (D-gal). Fisetin (Fis), a natural compound with antioxidant and anti-inflammatory properties, has potential for neurodegeneration management, but its low bioavailability limits clinical applications. To address this, we synthesized and characterized Pluronic-2-Acrylamido-2-methylpropane sulfonic acid (PLUR-PAMPS) nanogels using gamma radiation and successfully loaded Fis onto them (Fis-PLUR-PAMPS). The optimal formulation exhibited minimal particle size, a highly acceptable polydispersity index, and the highest zeta-potential, enhancing stability and solubilization efficiency. Our goal was to improve Fis's bioavailability and assess its efficacy against AlCl3/D-gal-induced AD. Male albino Wistar rats were pre-treated orally with Fis (40 mg/kg) or Fis-PLUR-PAMPS for seven days, followed by a seven-day intraperitoneal injection of AlCl3 and D-gal. Behavioral assessments, histopathological analysis, and biochemical evaluation of markers related to AD pathology were conducted. Results demonstrated that Fis-PLUR-PAMPS effectively mitigated cognitive impairments and neurodegenerative signs induced by AlCl3/D-gal. These findings suggest that Fis-PLUR-PAMPS nanogels enhance Fis's bioavailability and therapeutic efficacy, offering a promising approach for AD management.

Cognitive Impairment and Associated Factors Among Adults with Type 2 Diabetes Mellitus in Bahir Dar City Referral Hospitals, 2021: Cross-Sectional Study

Background: Neurocognitive impairment, characterized by reduced performance in various cognitive domains, has been significantly linked with glycemic control in type 2 diabetes mellitus (T2DM) patients. Poorly controlled diabetes often results in decreased cognitive abilities, and a longer duration of the disease is associated with lower cognitive levels. Objective: This study aimed to evaluate the prevalence of cognitive impairment in adults with T2DM and identify related factors. Methods: An institution-based cross-sectional study was conducted among 421 adults with T2DM. A systematic random sampling was used to select study participants in two referral hospitals in Bahir Dar, Ethiopia. Standardized Mini-Mental State Examination tool was used. Binary logistic regression was used. Significance was declared at p value≤0.05 with 95% confidence interval. Results: Over a quarter (27.6%) of participants were identified as cognitively impaired. Factors associated with lower cognitive status included older age, being single, lower education level, farming occupation, presence of comorbidity, and engagement in moderate physical activity. Conclusions: In conclusion, the prevalence of cognitive impairment among T2DM patients is a growing concern. Several risk factors have been identified like age group, marital status, education level, occupation, presence of comorbidity, and moderate physical activities. The impact of cognitive impairment on the quality of life and functional abilities of T2DM patients should not be underestimated.

Acute nicotine vapor normalizes sensorimotor gating and reduces locomotor activity deficits in HIV-1 transgenic rats.

Despite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and neuroinflammation. PWH exhibit high smoking rates, possibly due to neuroprotective, anti-inflammatory, and cognitive-enhancing effects of nicotine, suggesting potential self-medication. Here, we tested the effects of acute nicotine vapor exposure on translatable measures of sensorimotor gating and exploratory behavior in the HIV-1 transgenic (HIV-1Tg) rat model of HIV. Male and female HIV-1Tg and F344 control rats (n=57) were exposed to acute nicotine or vehicle vapor. Sensorimotor gating was assessed using prepulse inhibition (PPI) of the acoustic startle response, and exploratory behavior was evaluated using the behavioral pattern monitor (BPM). Vehicle-treated HIV-1Tg rats exhibited PPI deficits at low prepulse intensities compared to F344 controls, as seen previously. No PPI deficits were observed in nicotine-treated HIV1-Tg rats, however. HIV-1Tg rats were hypoactive in the BPM relative to controls, whilst nicotine vapor increased activity and exploratory behavior across genotypes. Cotinine analyses confirmed comparable levels of the primary metabolite of nicotine across genotypes. Previous findings of PPI deficits in HIV-1Tg rats were replicated and, importantly, attenuated by acute nicotine vapor. Evidence for similar cotinine levels suggest a nicotine-specific effect in HIV-1Tg rats. HIV-1Tg rats had reduced exploratory behavior compared to controls, attenuated by acute nicotine vapor. Therefore, acute nicotine may be beneficial for remediating sensorimotor and locomotor activity deficits in PWH. Future studies should determine the long-term effects of nicotine vapor on similar HIV/NCI-relevant behaviors.

Neurocognitive Function Domains Are Not Affected in Active Professional Male Footballers, but Attention Deficits and Impairments Are Associated with Concussion.

To determine the neurocognitive function of active professional male footballers, determine whether deficits/impairments exist, and investigate the association between previous concussion(s) and neurocognitive function. An observational cross-sectional study conducted via electronic questionnaires. The CNS Vital Signs online testing system was used to evaluate neurocognitive function. Of the 101 participants, 91 completed the neurocognitive function testing. Neurocognitive function domain deficits or impairments were unlikely in 54.5-89.1%, slight in 5.9-21.8%, moderate in 1.0-9.9%, and likely in 4.0-14.9% of participants. A history of zero concussions found a significant association between the neurocognitive index (Odds Ratio [OR] 0.6; 95% CI 0.2-0.4) and complex attention domain (OR 0.3; 95% CI 0.1-0.9), with 40% and 70% less odds, respectively, of deficit/impairment. Among the 54.5% who reported any number of concussions, there were increased odds of neurocognitive domain deficits/impairments for complex attention (CA) [3.4 times more] and simple attention (SA) [3.1 times more]. In the active professional male footballer, most neurocognitive functions do not have significant deficits/impairments. The odds of neurocognitive function deficit/impairment were significantly increased threefold for CA and SA in those who reported a history of any concussion(s).

Cognitive enhancing effect of rTMS combined with tDCS in patients with major depressive disorder: a double-blind, randomized, sham-controlled study

BackgroundCognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients.MethodsIn this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients’ cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients’ depressive symptoms at baseline and week 2.ResultsAfter 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups.ConclusionsrTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients.Trial registrationChinese Clinical Trial Registry (ChiCTR2100052122).

Dextrose gel prophylaxis for neonatal hypoglycaemia and neurocognitive function at early school age: a randomised dosage trial

ObjectiveTo investigate the effect of different doses of prophylactic dextrose gel on neurocognitive function and health at 6–7 years.DesignEarly school-age follow-up of the pre-hPOD (hypoglycaemia Prevention with Oral Dextrose) study.SettingSchools...

QOL-24. TREATMENT- AND TIME-RELATED IMPACT ON LONG-TERM NEUROCOGNITIVE OUTCOMES IN ADULT SURVIVORS OF A PEDIATRIC BRAIN TUMOR

Abstract Treatment for pediatric brain tumors has been associated with the risk of developing long-term neurocognitive impairment. However, it is not well understood which neurocognitive profiles exist within this population. We investigated neurocognitive functioning (NF) in survivors in early adulthood and aimed to assess the impact of radiotherapy dose (RTD) and time since treatment (TxT) on NF. Forty-six survivors of pediatric brain tumors (mean age 23.99±4.71, mean age at diagnosis 9.29±4.54) performed an extensive neurocognitive test battery resulting in intelligence (n=5), memory (n=2), and language (n=3) scores. NF in long-term survivors was compared to sex-, age-, and education-matched controls, and between the different treatment strategies (surgery-only n=19, chemotherapy n=8, radiotherapy n=11, or chemo-radiotherapy n=8). Furthermore, relation between max-RTD (range 40.28 – 61.61 Gy) as well as TxT and NF was assessed. Three ANCOVA models were tested, and false discovery rate (FDR) was applied. For all scales and domain scores, survivors scored lower compared to controls. Scores were significant lower on full scale intelligence (pfdr&amp;lt; 0.001), verbal comprehension (pfdr&amp;lt; 0.001), working memory (pfdr= 0.003), perceptual reasoning (pfdr&amp;lt; 0.001), processing speed (pfdr&amp;lt; 0.001), spoken word comprehension (pfdr= 0.001), and semantic word generation (pfdr= 0.036) compared to controls. NF was not significantly different between the different treatments, nor did the association with max-RTD reach significance. TxT was associated with verbal comprehension and spoken word comprehension; albeit significance was not retained after FDR correction. In this study, the overall survivor cohort scored lower on multiple cognitive outcomes. More detailed analysis of various risk factors might further elucidate the different neurocognitive profiles for this population. Furthermore, more detailed analysis of RTD distributions and affected brain structures may provide greater insight on the impact of radiotherapy on NF.

QOL-02. PREDICTING NEUROCOGNITIVE OUTCOMES AMONG CHILDREN EXPERIENCING VARYING DEGREES OF POSTOPERATIVE POSTERIOR FOSSA SYNDROME

Abstract BACKGROUND Postoperative posterior fossa syndrome (PFS) has historically been diagnosed as present vs. absent despite a continuum of severity in presentations. We recently demonstrated categorizing children into PFS1 (complete mutism) and PFS2 (diminished speech) has prognostic utility for neurological recovery. Given children who experience PFS are also at increased risk for neurocognitive impairments, we investigated whether these PFS variants predict neurocognitive outcomes while considering well-established risk factors (i.e., age and treatment intensity). METHODS Children treated for medulloblastoma at St. Jude on a prospective, risk-stratified protocol (SJMB12; NCT 01878617) were study eligible if they had at least two neurocognitive evaluations. SJMB12 participants received neurological and neurocognitive evaluations prior to irradiation and annually for 5 years. Neurocognitive outcomes included intellectual functioning (Wechsler Intelligence Scale for Children [WISC-IV] estimated IQ [EIQ]), processing speed (WISC-IV Processing Speed Index [PSI]), working memory (WISC-IV Working Memory Index [WMI]), and adaptive functioning (Behavior Assessment System for Children [BASC2] Activities of Daily Living [ADL]). RESULTS 149 patients (age at diagnosis= 10.7±5.6; 64% male; 9% 15Gy, 40% 23.4Gy, 51% ≥36Gy) were included. No significant differences between PFS1 (n=34) or PFS2 (n=16) compared to NonPFS (n=99) were identified in age, sex, or irradiation dose (ps&amp;gt;.05). Multivariable linear mixed models indicate NonPFS have better EIQ than PFS1 and PFS2 (p&amp;lt;.03), with EIQ improving over time (p=.01). NonPFS have better PSI than PFS1 and PFS2 (p&amp;lt;.001). PSI declines over time irrespective of age (p&amp;gt;.05); however, PSI declines for those receiving 36Gy while improving for those receiving 15Gy (p&amp;lt;.001). NonPFS have better WMI than PFS1 and PFS2 (p&amp;lt;.05); older age at diagnosis is associated with improvement in WMI over time (p&amp;lt;.0005). ADL declines only in PFS1 patients (p&amp;lt;.05). CONCLUSIONS PFS variants add value beyond established risk factors in predicting neurocognition. Severity of PFS, in addition to treatment intensity, predicts worse outcomes.

Suppression of HIV-TAT and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters

HIV-associated neurological disorder (HAND) is a serious complication of HIV infection marked by neurotoxicity induced by viral proteins like Tat. Substance abuse exacerbates neurocognitive impairment in people living with HIV. There is an urgent need for therapeutic strategies to combat HAND comorbid with Cocaine Use Disorder (CUD). Our analysis of HIV and cocaine-induced transcriptomes in primary cortical cultures revealed significant overexpression of the macrophage-specific gene aconitate decarboxylase 1 (Acod1). The ACOD1 protein converts the tricarboxylic acid intermediate cis-aconitate into itaconate during the activation of inflammation. Itaconate then facilitates cytokine production and activates anti-inflammatory transcription factors, shielding macrophages from infection-induced cell death. However, the immunometabolic function of itaconate was unexplored in HIV and cocaine-exposed microglia. We assessed the potential of 4-octyl-itaconate (4OI), a cell-penetrable ester form of itaconate known for its anti-inflammatory properties. When primary cortical cultures exposed to Tat and cocaine were treated with 4OI, microglial cell number increased and the morphological altercations induced by Tat and cocaine were reversed. Microglial cells also appeared more ramified, resembling the quiescent microglia. 4OI treatment inhibited secretion of the proinflammatory cytokines IL-1α, IL-1β, IL-6, and MIP1-α induced by Tat and cocaine. Transcriptome profiling determined that Nrf2 target genes were significantly activated in Tat and 4OI treated cultures relative to Tat alone. Further, genes associated with cytoskeleton dynamics in inflammatory microglia were downregulated by 4OI treatment. Together, the results strongly suggest 4-octyl-itaconate holds promise as a potential candidate for therapeutic development to treat HAND coupled with CUD comorbidities.Graphical Model of 4OI-mediated neuroprotection against Tat-Cocaine toxicity. Tat and Tat-Cocaine treatment induce neuronal damage, which is mitigated by 4OI through microglia cells. This cartoon shows the reduction of harmful effects such as pro-inflammatory cytokine release, upregulation of P2R, PDE, and Acod1 by the presence of 4OI. This ester modified itaconate triggers anti-inflammatory responses and activates antioxidant pathways

Neurocognitive and Neuropsychiatric Sequelae in Long COVID-19 Infection.

Objective: To characterize the cognitive profile of long COVID-19 subjects and its possible association with clinical symptoms, emotional disturbance, biomarkers, and disease severity. Methods: We performed a single-center cross-sectional cohort study. Subjects between 20 and 60 years old with confirmed COVID-19 infection were included. The assessment was performed 6 months following hospital or ambulatory discharge. Excluded were those with prior neurocognitive impairment and severe neurological/neuropsychiatric disorders. Demographic and laboratory data were extracted from medical records. Results: Altogether, 108 participants were included, 64 were male (59.25%), and the mean age was 49.10 years. The patients were classified into four groups: non-hospitalized (NH, n = 10), hospitalized without Intensive Care Unit (ICU) or oxygen therapy (HOSPI, n = 21), hospitalized without ICU but with oxygen therapy (OXY, n = 56), and ICU (ICU, n = 21) patients. In total, 38 (35.18%) reported Subjective Cognitive Complaints (SCC). No differences were found considering illness severity between groups. Females had more persistent clinical symptoms and SCC than males. Persistent dyspnea and headache were associated with higher scores in anxiety and depression. Persistent fatigue, anxiety, and depression were associated with worse overall cognition. Conclusions: No cognitive impairment was found regarding the severity of post-COVID-19 infection. SCC was not associated with a worse cognitive performance, but with higher anxiety and depression. Persistent clinical symptoms were frequent independent of illness severity. Fatigue, anxiety, and depression were linked to poorer cognitive function. Tests for attention, processing speed, and executive function were the most sensitive in detecting cognitive changes in these patients.

Tensor-valued diffusion MRI detects brain microstructure changes in HIV infected individuals with cognitive impairment.

Despite advancements, the prevalence of HIV-associated neurocognitive impairment remains at approximately 40%, attributed to factors like pre-cART (combination antiretroviral therapy) irreversible brain injury. People with HIV (PWH) treated with cART do not show significant neurocognitive changes over relatively short follow-up periods. However, quantitative neuroimaging may be able to detect ongoing subtle microstructural changes. This study aimed to investigate the sensitivity of tensor-valued diffusion encoding in detecting such changes in brain microstructural integrity in cART-treated PWH. Additionally, it explored relationships between these metrics, neurocognitive scores, and plasma levels of neurofilament light (NFL) chain and glial fibrillary acidic protein (GFAP). Using MRI at 3T, 24 PWH and 31 healthy controls underwent cross-sectional examination. The results revealed significant variations in b-tensor encoding metrics across white matter regions, with associations observed between these metrics, cognitive performance, and blood markers of neuronal and glial injury (NFL and GFAP). Moreover, a significant interaction between HIV status and imaging metrics was observed, particularly impacting total cognitive scores in both gray and white matter. These findings suggest that b-tensor encoding metrics offer heightened sensitivity in detecting subtle changes associated with axonal injury in HIV infection, underscoring their potential clinical relevance in understanding neurocognitive impairment in PWH.

Late events after anti-CD19 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

The short-term complications from chimeric antigen receptor T-cell therapy (CART) are well characterized, but the long-term complications still need to be further investigated. Therefore, herein, we will review the currently available literature published on the late adverse events following CART. We reviewed published data available from pivotal trials and real-world experiences with anti-CD19 CART (CART19) for adults with lymphoma. We defined late events as occurring or persisting beyond 1 month after CART infusion. We focused our literature review on the following late-event outcomes post-CART19: cytopenia, immune reconstitution, infections, and subsequent malignancies. Grade 3-4 cytopenia beyond 30 days occurs in 30%-40% of patients and beyond 90 days in 3%-22% of patients and is usually managed with growth-factor and transfusion support, along with neutropenic prophylaxis. B-cell aplasia and hypogammaglobulinemia are expected on-target off-tumor effects of CART19, 44%-53% of patients have IgG < 400 mg/dL, and approximately 27%-38% of patients receive intravenous immunoglobulin (IVIG) replacement. Infections beyond the initial month from CART19 are not frequent and rarely severe, but they are more prevalent and severe when patients receive subsequent therapies post-CART19 for their underlying disease. Late neurotoxicity and neurocognitive impairment are uncommon, and other causes should be considered. T-cell lymphoma (TCL) after CART is an extremely rare event and not necessarily related to CAR transgene. Myeloid neoplasm is not rare post-CART, but unclear causality given heavily pretreated patient population is already at risk for therapy-related myeloid neoplasm. CART19 is associated with clinically significant long-term effects such as prolonged cytopenia, hypogammaglobulinemia, and infections that warrant clinical surveillance, but they are mostly manageable with a low risk of non-relapse mortality. The risk of subsequent malignancies post-CART19 seems low, and the relationship with CART19 and/or prior therapies is unclear; but regardless of the possible causality, this should not impact the current benefit-risk ratio of CART19 for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

Neurocognitive Impairment in Long COVID: A Systematic Review

Abstract Objective Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory infectious disease, it has also been associated with a wide range of other clinical manifestations. It is widely accepted in the scientific community that many patients after recovery continue to experience COVID-19-related symptoms, including cognitive impairment. The aim of this systematic review was to investigate the cognitive profile of patients with long-COVID syndrome. Methods A systematic search of empirical studies was conducted through the PubMed/Medline and Scopus electronic databases. Cross-sectional and longitudinal studies published between 2020 and 2023 were included. Results Of the 516 studies assessed for eligibility, 36 studies met the inclusion criteria. All included studies support the presence of persistent cognitive changes after COVID-19 disease. Executive function, memory, attention, and processing speed appear to be the cognitive domains that are predominantly associated with long-COVID syndrome, whereas language is an area that has not been sufficiently investigated. Conclusions In this review, the high frequency of cognitive impairment after COVID-19 is evident. If we consider that cognitive functioning affects our ability to live independently and is a key determinant of our quality of life, it is imperative to precisely define those factors that may induce cognitive impairment in COVID-19 survivors, with the ultimate goal of early diagnosis of cognitive changes and, consequently, the development of targeted rehabilitation interventions to address them.

Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy.

Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF). IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study. Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) more than 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIV pol/gag -DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair. Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. Nine of 18 (50%) were female sex-at-birth, and 14 of 18 (78%) were black. Median (range) age was 20 years (13-27), time on ART was 18.3 years (8.0-25.5), and FCCS was 68 (53-80). HIV-DNA was detected in PBMCs from all participants. In CSF, two of 18 (11%, 95% CI: 1.4-34.7%) participants had detectable cell-free HIV-RNA, while HIV gag or pol -DNA was detectable in 13 of 18 (72%, 95% confidence interval: 47-90). Detectable HIV-DNA in CSF was associated with male sex-at-birth ( P = 0.051), lower CD4 + cell count at enrollment ( P = 0.016), and higher PBMC HIV pol -DNA copies ( P = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection. We found that a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.

Cytosolic Escape of Mitochondrial DNA Triggers cGAS-STING Pathway-Dependent Neuronal PANoptosis in Response to Intermittent Hypoxia.

Intermittent hypoxia (IH) is the predominant pathophysiological disturbance in obstructive sleep apnea (OSA), characterized by neuronal cell death and neurocognitive impairment. We focus on the accumulated mitochondrial DNA (mtDNA) in the cytosol, which acts as a damage-associated molecular pattern (DAMP) and activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a known trigger for immune responses and neuronal death in degenerative diseases. However, the specific role and mechanism of the mtDNA-cGAS-STING axis in IH-induced neural damage remain largely unexplored. Here, we investigated the involvement of PANoptosis, a novel type of programmed cell death linked to cytosolic mtDNA accumulation and the cGAS-STING pathway activation, in neuronal cell death induced by IH. Our study found that PANoptosis occurred in primary cultures of hippocampal neurons and HT22 cell lines exposed to IH. In addition, we discovered that during IH, mtDNA released into the cytoplasm via the mitochondrial permeability transition pore (mPTP) activates the cGAS-STING pathway, exacerbating PANoptosis-associated neuronal death. Pharmacologically inhibiting mPTP opening or depleting mtDNA significantly reduced cGAS-STING pathway activation and PANoptosis in HT22 cells under IH. Moreover, our findings indicated that the cGAS-STING pathway primarily promotes PANoptosis by modulating endoplasmic reticulum (ER) stress. Inhibiting or silencing the cGAS-STING pathway substantially reduced ER stress-mediated neuronal death and PANoptosis, while lentivirus-mediated STING overexpression exacerbated these effects. In summary, our study elucidates that cytosolic escape of mtDNA triggers cGAS-STING pathway-dependent neuronal PANoptosis in response to IH, mainly through regulating ER stress. The discovery of the novel mechanism provides theoretical support for the prevention and treatment of neuronal damage and cognitive impairment in patients with OSA.

Long-Term Follow-Up of Apert Syndrome Following Mid-Face Advancement: More Than 3 Decades Later.

Apert syndrome is characterized by craniosynostosis, a hypoplastic mid-face, skeletal abnormalities, symmetric syndactyly of the hands and feet, and a degree of neurocognitive impairment. Long-term outcomes of patients who have undergone surgical correction of Apert syndrome are limited. The authors present the case of a 73-year-old female with Apert syndrome, with follow-up of more than 3 decades following a fronto-orbital advancement and Le Fort III advancement. Clinical and radiologic images demonstrate a degree of skeletal resorption and relapse that is likely unavoidable. This provides insight into the long-term skeletal stability and esthetic outcomes for patients with Apert syndrome.

Neurocognitive Impairment among HIV-Infected Participants on Methadone for IV-Heroin use in Yunnan, China Relates to AIDS Status and Depression Severity, not Patterns of Substance use

We used a comprehensive and culturally normed battery of Neurocognitive (NC) tests to evaluate NC impairment (NCI) in 406 adults with prior IV heroin use who were in a government-supervised methadone maintenance program in Yunnan province, China. Participants included 202 without HIV infection, 57 with AIDS, and 147 HIV+ without AIDS (“nonAIDS group”). The AIDS group had higher proportions of individuals with global NCI (38.6%) relative to nonAIDS (15.7%) and HIV- participants (17.3%; ps &lt; 0.01). The AIDS group performed worse than the non AIDS group globally (&lt; 0.001), and in the domains of executive functioning (ps = 0.001), learning (ps = 0.035), and speeded information processing (ps = 0.0002). Despite the lack of difference in prevalence of NCI between non AIDS and HIV- groups, the non AIDS group showed impairment in memory and complex motor domains relative to the HIV- group (p = 0.03). In People With HIV (PWH), NCI was associated with more severe depression symptoms and HIV disease characteristics (duration of illness, CD4 nadir, AIDS status). Nearly all participants were HCV infected. Alcohol use disorder diagnoses, non-invasive indications of liver fibrosis, and characteristics of prior heroin use were not associated with NCI. PWH with NCI had worse daily functioning, as indexed by unemployment (ps = 0.016) and reported increased cognitive difficulties in daily life (ps = 0.016). These results highlight the importance of early HIV diagnosis and treatment to avoid HIV disease progression, particularly among IV drug users, with the goal of protecting NC abilities, everyday functioning, and life quality in infected individuals.

The Tower of London task in children and adolescents with neuropsychiatric disorders

ABSTRACT The Tower of London, Drexel Version, Second Edition (TOL-DX) is purported to measure multiple aspects of executive functions, although it also possesses inherent non-executive demands. Such complexity makes it useful in detecting impairment but difficult in interpreting the neurocognitive cause of impairment, particularly in children. This study investigated the developmental, neurocognitive, and symptom correlates of the TOL-DX in children and adolescents with neuropsychiatric disorders. Two-hundred and thirty-three children and adolescents (7–21 years old) completed the TOL-DX during a neuropsychological evaluation as part of clinical care within a children’s psychiatric hospital. Pearson correlation, regression models, and receiver operating characteristic curve (ROC) analyses examined the association among variables. Visuospatial and executive functions (EF) were most consistently related to total moves, execution time, and violations. TOL-DX variables were associated with attention in younger participants and EF in older participants. No TOL-DX scores were related to parent-reported symptoms. The TOL-DX possesses inherent visuospatial and attention/executive demands in children and adolescents which are difficult to differentiate, differ by age group, and not associated to clinical symptoms. Taken together, the TOL-DX is complex to interpret, but psychometrically sound and sensitive to neurocognitive impairment in children and adolescents with transdiagnostic neuropsychiatric disorders.

Retraction Note: Neurocognitive impairment and patient-proxy agreement on health-related quality of life evaluations in recurrent high-grade glioma patients.

Retraction Note: Neurocognitive impairment and patient-proxy agreement on health-related quality of life evaluations in recurrent high-grade glioma patients.