Total Cognitive Score Research Articles

Tensor-valued diffusion MRI detects brain microstructural abnormalities 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. In this study, we hypothesized that tensor-valued diffusion encoding metrics would provide greater sensitivity than conventional diffusion tensor imaging (DTI) metrics in detecting HIV-associated brain microstructural injury. We further hypothesized that tensor-valued metrics would exhibit stronger associations with blood markers of neuronal and glial injury, such as neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP), as well as with cognitive performance. Using MRI at 3T, 24 PWH and 31 healthy controls underwent cross-sectional examination. The results revealed significant variations in tensor-valued diffusion encoding metrics across white matter regions, with associations observed between these metrics, cognitive performance, NFL and GFAP. Moreover, a significant interaction between HIV status and imaging metrics in gray and white matter was observed, particularly impacting total cognitive scores. Of interest, DTI metrics were less likely to be associated with HIV status than tensor-valued diffusion metrics. These findings suggest that tensor-valued diffusion encoding metrics offer heightened sensitivity in detecting subtle changes associated with axonal injury in HIV infection. Longitudinal studies are needed to further evaluate responsiveness of tensor-valued diffusion b-tensor encoding metrics in the contest HIV-associate mild chronic neuroinflammation.

Leveraging digital skills to reduce cognitive strain: Implications for academic self-efficacy in medical education

BackgroundDigital literacy influences academic behaviors, especially in medical education, where students encounter considerable academic challenges. However, the effects of this phenomenon on academic self-efficacy and cognitive load remain inadequately understood. ObjectivesThis research explores the relationships between digital literacy and academic self-efficacy, emphasizing the mediating role of cognitive load and its various dimensions among medical students in Islamabad, Pakistan. MethodsA descriptive cross-sectional survey was conducted from seven medical colleges in Islamabad, Pakistan, from October to December 2023. The research employed meticulously validated measurement tools encompassing a digital literacy scale, academic self-efficacy scale, and cognitive load scale and collected data on 633 medical students. Descriptive statistics and inferential testing (mediation analysis) were performed to investigate the direct and indirect relationships of the study variables. ResultsThe empirical results revealed that digital literacy significantly enhances academic self-efficacy both directly and indirectly. First, the total cognitive load score showed partial mediation (β = 0.165, p < 0.001). Then, individual subscale analysis revealed that intrinsic cognitive load (β = 0.147, p < 0.001) and extraneous cognitive load (β = 0.144, p < 0.001) were significant mediators. However, the mediation effect through self-perceived learning (β = 0.105, p = 0.361) was not supported, suggesting variability in how students perceive their learning gains or other influencing factors influencing this relationship, which warrants further investigation. ConclusionThe research finding underscores the crucial integration of digital literacy instruction into medical curriculums to bolster students' academic self-efficacy by adeptly managing cognitive load. While digital literacy notably reduces intrinsic and extraneous cognitive loads, its impact on perceived learning appears context-dependent and requires further exploration. Additional studies are needed to understand these relationships across educational settings and identify other potential influencing factors.

Non-classical monocyte levels correlate negatively with HIV-associated cerebral small vessel disease and cognitive performance.

Despite antiretroviral treatment (cART), aging people living with HIV (PWH) are more susceptible to neurocognitive impairment (NCI) probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, transmigration of inflammatory CD16+ monocytes through the altered blood brain barrier (BBB) may exacerbate cerebral small vessel disease (CSVD), a known cause of vascular cognitive impairment. PWH on cART (n=108) and age, sex, and Reynold's cardiovascular risk score-matched uninfected individuals (PWoH, n=111) were enrolled. This is a longitudinal observational study but only cross-sectional data from entry visit are reported. Neuropsychological testing and brain magnetic resonance imaging (MRI) were performed. CSVD was diagnosed by Fazekas score ≥1. Flow cytometric analyses of fresh whole blood were conducted to evaluate circulating levels of monocyte subsets (classical, intermediate, and non-classical) and markers of monocyte activation (CCR2, CD40, PSGL-1, TNFR2 and tissue factor). ELISAs were used to measure sCD14, ICAM, and Osteoprotegerin. Two-way analysis of variance (ANOVA), and linear regression models were performed to study the effects of HIV status, CSVD status, and their interaction to outcome variables such as cognitive score. Two-sample t-tests and correlation analyses were performed between and within PWoH with CSVD and PWH with CSVD participants. PWH with CSVD (n=81) had significantly lower total cognitive scores, higher levels of NCMs and soluble CD14 and intracellular adhesion molecule 1 (ICAM-1) as compared to PWoH with CSVD group (n=68). sCD14 and ICAM1 were positively correlated with each other indicating that monocyte and endothelial activation are associated with each other. Cognition was negatively correlated with NCMs, especially in the PWH with CSVD group. Among other blood biomarkers measured, osteoprotegerin levels showed mild negative correlation with cognitive performance in individuals with CSVD irrespective of HIV status. Elevated levels of NCMs may contribute to neuroinflammation, CSVD and subsequent cognitive impairment. This finding is of particular relevance in aging PWH as both HIV and aging are associated with increased levels of NCMs. NCMs may serve as a potential biomarker to address these comorbidities. Further longitudinal studies are needed to evaluate whether changes in NCM levels are associated with changes in CSVD burden and cognitive impairment.

Adverse childhood experiences and cognitive function in later life: the sequential mediating roles of education level and adult loneliness.

This study assesses the impact of adverse childhood experiences (ACEs) on the cognitive function of older adults. Furthermore, it examines the potential underlying mechanism involving education level and the subjective "feeling of loneliness" (FOL). Analyzing a population-based cohort sample from the China Health and Retirement Longitudinal Study database, 8,365 subjects aged 45 or older were interviewed in 2018. Ten ACEs indicators were measured using life history questionnaires assessed at 2014. FOL was assessed using a single item from 10-item Center for Epidemiological Studies Depression Scale (CESD-10). Cognitive function was assessed using a structured questionnaire comprising four dimensions: memory, orientation, computation, and visuospatial abilities. In the fully adjusted model, which accounted for age, gender, marital status, smoke, drink, rural residence, and education levels of both mothers and fathers, the linear regression analysis indicated that ACEs were inversely associated the lower education level (B = -0.058, 95% CI = -0.090, -0.026, p < 0.001), and ACEs were found to be linked to an elevated risk of FOL (B = 0.072, 95% CI = 0.056, 0.089, p < 0.001). In addition, ACEs was not significantly associated with cognitive function (B = -0.047, 95% CI = -0.108, 0.015, p = 0.136), but FOL was significantly associated with cognitive function (B = -0.483, 95% CI = -0.561, -0.404, p < 0.001). Mediation analysis revealed that education level and FOL sequentially and partially mediated the association between ACEs and the total cognitive score, with a proportion mediated of 52.58%. The evaluation of ACEs exposure was based on binary response options. This method limited our ability to explore various dimensions of adversity, such as ages of occurrence, severity, frequency, duration, and the extent of psychological effects at the time. Furthermore, the assessment of loneliness relied on a single item from the CESD-10, introducing a potential source of measurement error. Our study unveils a substantial association between ACEs and education level, as well as with FOL and cognitive function in the older adults. Moreover, education level and FOL serve as sequential mediating factors in the relationship between ACEs and cognitive function.

Impact of excessive daytime sleepiness on attention impairment in obstructive sleep apnea: a cross-sectional observational study.

This study aims to examine the relationship between excessive daytime sleepiness (EDS) and attention impairment in Chinese individuals with obstructive sleep apnea (OSA). A total of 1996 OSA patients with an apnea-hypopnea index (AHI) of ≥ 5 events per hour were included in this study. EDS was measured using the Epworth Sleepiness Scale (ESS), while cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). OSA patients with EDS demonstrated higher body mass index (BMI), comorbidities of hypertension and diabetes, decreased N3 sleep, increased AHI and ODI, as well as lower minimum oxygen saturation. Despite no significant differences in total cognitive scores assessed by MMSE and MoCA, individuals with comorbid sleepiness exhibited more evident attention deficits in the subdomains of MoCA. Stratified analysis indicated that regardless of age, educational level was the primary factor influencing attention in the AHI < =20 group. In the AHI > 20 group, attention impairment in patients younger than 40 remained significantly associated with education level, whereas for individuals aged 40 and above, attention deficits were associated with education level, age, and daytime sleepiness. The interaction analysis indicated that OSA severity modulated the impact of sleepiness on attention in patients aged 40 and above. A significant correlation was observed between EDS and attention deficits in Chinese individuals diagnosed with OSA, with a particular emphasis on patients aged 40 and above. The severity of OSA modulates the impact of sleepiness on attention in patients aged 40 and above.

DNA Methylation at C-Reactive Protein-Associated CpG Sites May Mediate the Pathway Between Educational Attainment and Cognition.

Growing evidence has linked inflammatory processes to cognitive decline and dementia. This work examines whether an epigenetic marker of C-reactive protein (CRP), a common clinical inflammatory biomarker, may mediate the relationship between educational attainment and cognition. We first evaluated whether 53 previously reported CRP-associated DNA methylation sites (CpGs) are associated with CRP, both individually and aggregated into a methylation risk score (MRSCRP), in 3298 participants from the Health and Retirement Study (HRS, mean age = 69.7 years). Forty-nine CpGs (92%) were associated with the natural logarithm of CRP in HRS after adjusting for age, sex, smoking, BMI, genetic ancestry, and white blood cell counts (p < .05), and each standard deviation increase in MRSCRP was associated with a 0.38 unit increase in lnCRP (p = 4.02E-99). In cross-sectional analysis, for each standard deviation increase in MRSCRP, total memory score and total cognitive score decreased, on average, by 0.28 words and 0.43 items, respectively (p < .001). Further, MRSCRP mediated 6.9% of the relationship between high school education and total memory score in a model adjusting for age, sex, and genetic ancestry (p < .05); this was attenuated to 2.4% with additional adjustment for marital status, APOE ε4 status, health behaviors, and comorbidities (p < .05). Thus, CRP-associated methylation may partially mediate the relationship between education and cognition at older ages. Further research is warranted to determine whether DNA methylation at these sites may improve current prediction models for cognitive impairment in older adults.

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.

Abnormalities of cortical stimulation strength-duration time constant in amyotrophic lateral sclerosis

ObjectivesStrength-duration time constant (SDTC) may now be determined for cortical motor neurones, with activity mediated by transient Na+ conductances. The present study determined whether cortical SDTC is abnormal and linked to the pathogenesis of amyotrophic lateral sclerosis. MethodsCortical SDTC and rheobase were estimated from 17 ALS patients using a controllable pulse parameter transcranial magnetic stimulation (cTMS) device. Resting motor thresholds (RMTs) were determined at pulse widths (PW) of 30, 45, 60, 90 and 120 µs and M−ratio of 0.1, using a figure-of-eight coil applied to the primary motor cortex. ResultsSDTC was significantly reduced in ALS patients (150.58 ± 9.98 µs; controls 205.94 ± 13.7 µs, P < 0.01). The reduced SDTC correlated with a rate of disease progression (Rho = -0.440, P < 0.05), ALS functional rating score (ALSFRS-R) score (Rho = 0.446, P < 0.05), and disease duration (R = 0.428, P < 0.05). The degree of change in SDTC was greater in patients with cognitive abnormalities as manifested by an abnormal total Edinburgh Cognitive ALS Screen score (140.5 ± 28.7 µs, P < 0.001) and ALS-specific subscore (141.7 ± 33.2 µs, P = 0.003). ConclusionsCortical SDTC reduction was associated with a more aggressive ALS phenotype, or with more prominent cognitive impairment. SignificanceAn increase in transient Na+ conductances may account for the reduction in SDTC, linked to the pathogenesis of ALS.

The role of clinical and demographic predictors for understanding the cognitive impairment in Spinal Cord Injury (SCI) patients.

Using a cross-sectional design, we extracted sociodemographic and clinical data from 488 Spinal Cord Injury (SCI) patients during their initial assessment before receiving intensive rehabilitation treatment. The primary objectives of this study were to ascertain the prevalence of cognitive impairment in the study sample and specify the key clinical and demographic predictors of cognitive functioning in SCI patients. Lucy Montoro Rehabilitation Institute (LMRI), University of Sao Paulo, Sao Paulo, Brazil. We utilized independent univariate and multivariate regression models with the Montreal Cognitive Assessment (MoCA) scale, adapted for individuals with visual impairment. Moreover, we consider scores from the execution tasks (visuospatial/executive) as the dependent variable. Our findings demonstrate that approximately 80% of the evaluated study sample exhibited cognitive impairment. Through the multivariate regression models, we show that several factors, including age, education, depression levels, and the use of analgesics and/or opioids, are significant predictors of total cognitive scores. These factors are independent of the clinical features associated with SCI, such as age, sex, education, and time since the injury. The results indicate a high prevalence of significant cognitive impairment within the sample, with age, education, depression levels, and the use of analgesics and/or opioids emerging as the primary predictors of total cognitive scores, independent of the clinical features correlated to SCI. These findings hold significant implications for both clinical research and practice, offering valuable guidance for comprehensive management throughout hospitalization and rehabilitation.

Assessing Cognition in CKD Using the National Institutes of Health Toolbox.

Chronic kidney disease (CKD) is largely an age-related clinical disorder with accelerated cognitive and cardiovascular aging. Cognitive impairment is a well-documented occurrence in midlife and older adults with CKD and affects multiple domains. We examined cognition function and potential sex differences in cognition in adults with CKD. We included 105 individuals (49.5% women) with CKD stage 3b-4 (eGFR 15-44 mL/min) from the Bicarbonate Administration in CKD Trial (NCT02915601). We measured cognitive function using the National Institutes of Health (NIH) Toolbox® Cognition Battery, which assesses cognitive and motor measures such as executive function, attention, memory, and dexterity. All study measures were collected and analyzed at the study baseline. The mean (SD) age and eGFR were 61 ± 12 years and 34.9 ± 9.8 mL/min/1.73m2. Overall, when compared to the NIH Toolbox reference population, participants scored, on average, below the 50th percentile across all cognitive domain tests and the dexterity test. Total cognition scores were also below the 50th percentile. Participants with stage 4 CKD had significantly lower fluid cognition scores compared to those with CKD stage 3b (β-Estimate -5.4 (95% CI-9.8 to -0.9); p=0.03). Female participants with CKD performed significantly better on the episodic memory tests and dexterity tests (dominant and non-dominant pegboard tests), and had higher crystallized cognition scores, on average, compared to males. Participants with CKD had detectable cognitive deficits in fluid cognition, dexterity, and total cognition. Additionally, sex differences in cognitive measures were found among people with CKD.

An unexpected interaction between diabetes and cardiovascular diseases on cognitive function: A cross-sectional study

ObjectiveImpaired cognitive function in older individuals significantly affects quality of life. The interaction between comorbid diabetes and cardiovascular disease (CVD) and its impact on cognitive impairment remains unclear. MethodsThis study analyzed 2564 subjects from the National Health and Nutrition Examination Survey dataset. Cognitive function was measured using various scores, including CERAD Total Score, CERAD Delayed Recall Score (CDRS), Animal Fluency Total Score, and Digit Symbol Score. Multiple regression models were constructed to explore the relationship between different diseases and cognitive function, considering covariates such as age, sex, education, body mass index, alcohol intake, smoking, physical activity, kidney function, and hypertension. ResultsAfter adjusting for multiple factors, the presence of CVD, diabetes, or both showed a significant negative association with the total cognitive score. The CDRS was associated with both CVD and diabetes. The Digit Symbol score was associated with the presence of CVD, diabetes, or both. No significant differences were found between patients with diabetes and CVD in cognitive test results. An interaction between CVD and diabetes was observed in relation to the CDRS but not in other test scores or the total score. ConclusionThe individual impact of each disease on cognitive function was not significant. However, an interaction between CVD and diabetes was found when both diseases coexisted, specifically in relation to delayed learning ability.

The structural–functional-connectivity coupling of the aging brain

Aging primarily affects memory and executive functions, a relationship that may be underpinned by the fact that almost all adults over 60 years old develop small vessel disease (SVD). The fact that a wide range of neuropathologies could only explain up to 43% of the variation in age-related cognitive impairment suggests that other factors, such as cognitive reserve, may play a role in the brain’s resilience against aging-related cognitive decline. This study aims to examine the relationship between structural–functional-connectivity coupling (SFC), and aging, cognitive abilities and reserve, and SVD-related neuropathologies using a cohort of n = 176 healthy elders from the Harvard Aging Brain Study. The SFC is a recently proposed biomarker that reflects the extent to which anatomical brain connections can predict coordinated neural activity. After controlling for the effect of age, sex, and years of education, global SFC, as well as the intra-network SFC of the dorsolateral somatomotor and dorsal attention networks, and the inter-network SFC between dorsolateral somatomotor and frontoparietal networks decreased with age. The global SFC decreased with total cognitive score. There were significant interaction effects between years of education versus white matter hyperintensities and between years of education versus cerebral microbleeds on inter-network SFC. Enlarged perivascular space in basal ganglia was associated with higher inter-network SFC. Our results suggest that cognitive ability is associated with brain coupling at the global level and cognitive reserve with brain coupling at the inter-functional-brain-cluster level with interaction effect from white matter hyperintensities and cerebral microbleed in a cohort of healthy elderlies.

The association between indoor air pollution from solid fuels and cognitive impairment: a systematic review and meta-analysis.

This study aimed to comprehensively and methodically evaluate the correlation between cognitive impairment and indoor air pollution from solid fuel used for cooking/heating. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched up to December January 2023. 13 studies from three countries with a total of 277,001 participants were enrolled. A negative correlation was discovered between solid fuel usage for cooking and total cognitive score (β=-0.73, 95 % CI: -0.90 to -0.55) and episodic memory score (β=-0.23, 95 % CI: -0.30 to -0.17). Household solid fuel usage for cooking was considerably associated with a raised risk of cognitive impairment (HR=1.31, 95 % CI: 1.09-1.57) and cognitive decline (HR=1.24, 95 % CI: 1.18-1.30). Compared to continuous solid fuel use for cooking, sustained use of clean fuel and switching from solid fuel to clean fuel were associated with a lower risk of cognitive decline (OR=0.55, 95 % CI: 0.42-0.73; OR=0.81, 95 % CI: 0.71-0.93). A negative association was found between solid fuel usage for heating and total cognitive score (β=-0.43, 95 % CI: -0.59 to -0.26) and episodic memory score (β=-0.22, 95 % CI: -0.34 to -0.10). Our research provided evidence that exposure to indoor air pollution from solid fuel is a potential cause of cognitive impairment and cognitive decline. Making the switch from solid fuels to cleaner fuels could be an important step in preventing cognitive impairment in the elderly.

Distinct neuronal circuits mediate cortical hyperexcitability in amyotrophic lateral sclerosis.

Cortical hyperexcitability is an important pathophysiological mechanism in amyotrophic lateral sclerosis (ALS), reflecting a complex interaction of inhibitory and facilitatory interneuronal processes that evolves in the degenerating brain. The advances in physiological techniques have made it possible to interrogate progressive changes in the motor cortex. Specifically, the direction of transcranial magnetic stimulation (TMS) stimulus within the primary motor cortex can be utilized to influence descending corticospinal volleys and to thereby provide information about distinct interneuronal circuits. Cortical motor function and cognition was assessed in 29 ALS patients with results compared to healthy volunteers. Cortical dysfunction was assessed using threshold-tracking TMS to explore alterations in short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), the index of excitation and stimulus response curves using a figure-of-eight coil with the coil oriented relative to the primary motor cortex in a posterior-anterior, lateral-medial and anterior-posterior direction. Mean SICI, between interstimulus interval of 1-7 ms, was significantly reduced in ALS patients compared to healthy controls when assessed with the coil oriented in posterior-anterior (P = 0.044) and lateral-medial (P = 0.005) but not the anterior-posterior (P = 0.08) directions. A significant correlation between mean SICI oriented in a posterior-anterior direction and the total Edinburgh Cognitive and Behavioural ALS Screen score (Rho = 0.389, P = 0.037) was evident. In addition, the mean SICF, between interstimulus interval 1-5 ms, was significantly increased in ALS patients when recorded with TMS coil oriented in posterior-anterior (P = 0.035) and lateral-medial (P < 0.001) directions. In contrast, SICF recorded with TMS coil oriented in the anterior-posterior direction was comparable between ALS and controls (P = 0.482). The index of excitation was significantly increased in ALS patients when recorded with the TMS coil oriented in posterior-anterior (P = 0.041) and lateral-medial (P = 0.003) directions. In ALS patients, a significant increase in the stimulus response curve gradient was evident compared to controls when recorded with TMS coil oriented in posterior-anterior (P < 0.001), lateral-medial (P < 0.001) and anterior-posterior (P = 0.002) directions. The present study has established that dysfunction of distinct interneuronal circuits mediates the development of cortical hyperexcitability in ALS. Specifically, complex interplay between inhibitory circuits and facilitatory interneuronal populations, that are preferentially activated by stimulation in posterior-to-anterior or lateral-to-medial directions, promotes cortical hyperexcitability in ALS. Mechanisms that underlie dysfunction of these specific cortical neuronal circuits will enhance understanding of the pathophysiological processes in ALS, with the potential to uncover focussed therapeutic targets.

Investigating amplitude of low-frequency fluctuation and possible links with cognitive impairment in childhood and adolescence onset schizophrenia: a correlation study.

Cognitive impairment (CI) is a distinctive characteristic of schizophrenia, with evidence suggesting that childhood and adolescence onset schizophrenia (CAOS), representing severe but rare forms of schizophrenia, share continuity with adult-onset conditions. While relationships between altered brain function and CI have been identified in adults with schizophrenia, the extent of brain function abnormalities in CAOS remains largely unknown. In this study, we employed resting-state functional magnetic resonance imaging (rs-fMRI) to investigate functional alterations in brain areas among patients with CAOS. To assess CI across multiple cognitive domains, we utilized the Stroop Color and Word Tests (SCWT) and MATRICS Consensus Cognitive Battery (MCCB) tests. Our objective was to explore the associations between functional CI and the amplitude of low-frequency fluctuation (ALFF) levels in these patients. We enrolled 50 patients diagnosed with CAOS and 33 healthy controls (HCs) matched for sex and age. Cognitive functions were assessed using the MCCB and SCWT methods. Rs-fMRI data were acquired using gradient-echo echo-planar imaging sequences. Voxel-based ALFF group maps were compared through two-sample t-tests in SPM8. Subsequently, correlation analyses were conducted to identify associations between ALFF levels and cognitive scores. In comparison to HCs, patients exhibited significantly increased ALFF levels in the right fusiform gyrus, frontal lobe, and caudate, as well as the left frontal lobe and caudate. Conversely, reduced ALFF levels were observed in the temporal and left medial frontal lobes. Significant differences were identified between HCs and patients in terms of total cognitive scores, ALFF levels, and domain scores. All test scores were decreased, except for TMA. Correlation analyses between ALFF levels and cognitive functions in patients with CAOS differed from those in HCs. Pearson correlation analyses revealed positive associations between Brief Visuospatial Memory Test - Revised (BVMT-R) scores and ALFF levels in the left medial frontal gyrus. Digital Span Test (DST) scores were negatively correlated with ALFF levels in the right caudate, and Maze Test values were negatively correlated with levels in the left caudate. However, Pearson correlation analyses in HCs indicated that color and Hopkins Verbal Learning Test (HVLT-R) scores positively correlated with ALFF levels in the left frontal lobe, while color-word and symbol coding scores negatively correlated with levels in the right caudate. Altered ALFF levels in the brain may be linked to cognitive impairment (CI) in patients with CAOS. We highlighted the pathophysiology of schizophrenia and provide imaging evidence that could potentially aid in the diagnosis of CAOS.

The use of synaptic biomarkers in cerebrospinal fluid to differentiate behavioral variant of frontotemporal dementia from primary psychiatric disorders and Alzheimer’s disease

BackgroundLack of early molecular biomarkers in sporadic behavioral variants of frontotemporal dementia (bvFTD) and its clinical overlap with primary psychiatric disorders (PPD) hampers its diagnostic distinction. Synaptic dysfunction is an early feature in bvFTD and identification of specific biomarkers might improve its diagnostic accuracy. Our goal was to understand the differential diagnostic potential of cerebrospinal fluid (CSF) synaptic biomarkers in bvFTD versus PPD and their specificity towards bvFTD compared with Alzheimer’s disease (AD) and controls. Additionally, we explored the association of CSF synaptic biomarkers with social cognition, cognitive performance, and disease severity in these clinical groups.MethodsParticipants with probable bvFTD (n = 57), PPD (n = 71), AD (n = 60), and cognitively normal controls (n = 39) with available CSF, cognitive tests, and disease severity as frontotemporal lobar degeneration-modified clinical dementia rating scale (FTLD-CDR) were included. In a subset of bvFTD and PPD cases, Ekman 60 faces test scores for social cognition were available. CSF synaptosomal-associated protein 25 (SNAP25), neurogranin (Ng), neuronal pentraxin 2 (NPTX2), and glutamate receptor 4 (GluR4) were measured, along with neurofilament light (NfL), and compared between groups using analysis of covariance (ANCOVA) and logistic regression. Diagnostic accuracy was assessed using ROC analyses, and biomarker panels were selected using Wald’s backward selection. Correlations with cognitive measures were performed using Pearson’s partial correlation analysis.ResultsNPTX2 concentrations were lower in the bvFTD group compared with PPD (p < 0.001) and controls (p = 0.003) but not compared with AD. Concentrations of SNAP25 (p < 0.001) and Ng (p < 0.001) were elevated in patients with AD versus those with bvFTD and controls. The modeled panel for differential diagnosis of bvFTD versus PPD consisted of NfL and NPTX2 (AUC = 0.96, CI: 0.93–0.99, p < 0.001). In bvFTD versus AD, the modeled panel consisted of NfL, SNAP25, Ng, and GluR4 (AUC = 0.86, CI: 0.79–0.92, p < 0.001). In bvFTD, lower NPTX2 (Pearson’s r = 0.29, p = 0.036) and GluR4 (Pearson’s r = 0.34, p = 0.014) concentrations were weakly associated with worse performance of total cognitive score. Lower GluR4 concentrations were also associated with worse MMSE scores (Pearson’s r = 0.41, p = 0.002) as well as with worse executive functioning (Pearson’s r = 0.36, p = 0.011) in bvFTD. There were no associations between synaptic markers and social cognition or disease severity in bvFTD.ConclusionOur findings of involvement of NTPX2 in bvFTD but not PPD contribute towards better understanding of bvFTD disease pathology.

Long-term cognitive dysfunction after COVID ARDS

Background: COVID-19 acute respiratory distress syndrome (C-ARDS) survivors suffer from long-term physical complications. However, at the time of this study limited data are available on possible long-term cognitive impairment. Objectives: We hypothesized that COVID-19 ICU patients perform worse on cognitive tasks 6 months after admission, in comparison to reference values of a healthy population. Design: Two-center cohort study with a six months’ time horizon. Patients: Patients admitted to the ICU for COVID-19 associated respiratory failure between March and June 2020. Setting: Post-ICU follow up. Methods and main outcome measures: The primary measure was the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) score (with lower values indicating worse global cognition). The secondary outcome measure was the Trail Making Test (TMT) Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive functions). The Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE, on a scale from 1.0 to 5.0, with 5.0 indicating severe cognitive impairment) was taken for not patients not fluent in Dutch. Results: 117 COVID-19 patients were admitted to the ICU, of whom 32 patients (27%) died within 6 months. 67/85 (79%) patients participated in the cohort study. COVID-19 survivors had lower total RBANS cognition scores than the age-adjusted population norms (n=45). Fifteen (33%) patients had a global cognition score 1.5 SD below the population means. RBANS-subscale performance showed that both memory (immediate and delayed recall) and attention were at minus 1 SD below normative means, while language and visuospatial cognition were unaffected. Median TMT B score was 40 (IQR 10-65) (n=45). There were elevated scores of the short form IQCODE (mean 3.4 (SD 0.4). Conclusions: Our results suggests that COVID-19 ARDS negatively affects long-term cognitive function. Trial registration: ClinicalTrials.gov NCT04593069.

Temporal evolution of electrographic seizures in newborn infants with hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia: a secondary analysis of the ANSeR studies

Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome. This secondary analysis included newborn infants recruited from eight European tertiary neonatal intensive care units for two multicentre studies (a randomised controlled trial [NCT02431780] and an observational study [NCT02160171]). Infants were born at 36+0 weeks of gestation with moderate or severe hypoxic-ischaemic encephalopathy and underwent therapeutic hypothermia with prolonged conventional video-electroencephalography (EEG) monitoring for 10 h or longer from the start of rewarming. Seizure burden characteristics were calculated based on electrographic seizures annotations: hourly seizure burden (minutes of seizures within an hour) and total seizure burden (minutes of seizures within the entire recording). We categorised infants into those with electrographic seizures during active cooling only, those with electrographic seizures during cooling and rewarming, and those without seizures. Neurodevelopmental outcomes were determined using the Bayley's Scales of Infant and Toddler Development, Third Edition (BSID-III), the Griffiths Mental Development Scales (GMDS), or neurological assessment. An abnormal outcome was defined as death or neurodisability at 2 years. Neurodisability was defined as a composite score of 85 or less on any subscales for BSID-III, a total score of 87 or less for GMDS, or a diagnosis of cerebral palsy (dyskinetic cerebral palsy, spastic quadriplegia, or mixed motor impairment) or epilepsy. Of 263 infants recruited between Jan 1, 2011, and Feb 7, 2017, we included 129 infants: 65 had electrographic seizures (43 during active cooling only and 22 during and after active cooling) and 64 had no seizures. Compared with infants with seizures during active cooling only, those with seizures during and after active cooling had a longer seizure period (median 12 h [IQR 3-28] vs 68 h [35-86], p<0·0001), more seizures (median 12 [IQR 5-36] vs 94 [24-134], p<0·0001), and higher total seizure burden (median 69 min [IQR 22-104] vs 167 min [54-275], p=0·0033). Hourly seizure burden peaked at about 20-24 h in both groups, and infants with seizures during and after active cooling had a secondary peak at 85 h of age. When combined, worse EEG background (major abnormalities and inactive background) at 12 h and 24 h were associated with the seizure group: compared with infants with a better EEG background (normal, mild, or moderate abnormalities), infants with a worse EEG background were more likely to have seizures after cooling at 12 h (13 [54%] of 24 vs four [14%] of 28; odds ratio 7·09 [95% CI 1·88-26·77], p=0·0039) and 24 h (14 [56%] of 25 vs seven [18%] of 38; 5·64 [1·81-17·60], p=0·0029). There was a significant relationship between EEG grade at 12 h (four categories) and seizure group (p=0·020). High total seizure burden was associated with increased odds of an abnormal outcome at 2 years of age (odds ratio 1·007 [95% CI 1·000-1·014], p=0·046), with a medium negative correlation between total seizure burden and BSID-III cognitive score (rS=-0·477, p=0·014, n=26). Overall, half of infants with hypoxic-ischaemic encephalopathy had electrographic seizures and a third of those infants had seizures beyond active cooling, with worse outcomes. These results raise the importance of prolonged EEG monitoring of newborn infants with hypoxic-ischaemic encephalopathy not only during active cooling but throughout the rewarming phase and even longer when seizures are detected. Wellcome Trust, Science Foundation Ireland, and the Irish Health Research Board.

The effectiveness of egg supplementation on nutritional status, physical fitness and cognition of school-aged children (8–12 Years) in Ho Municipality, Ghana

BackgroundEgg is a cheap source of essential micronutrients and high-quality protein, which can contribute to the daily nutritional needs of children, support their growth and brain development. Aim: The study evaluated the effectiveness of egg supplementation on nutritional status, physical fitness, and cognition of school-aged Children (8–12 Years) in Ho Municipality, Ghana. MethodsA school-based, double-blind randomized controlled trial design was adopted. Children aged 8 to 12 years from government-run primary schools were randomly allocated to receive either egg supplementation three times a week for three months or no supplementation at all for three months. Dietary intakes using a repeated 24-h dietary recall, Raven's cognition test, fitness level, BMI-for-age, and serum levels of ferritin, zinc, and albumin were assessed at baseline and after the intervention. ResultsAt pre-intervention, mean intake of several nutrients, including energy, CHO, protein, fat, iron zinc and folate were significantly higher in the intervention group. Post-intervention, these differences significantly increased for protein, fat, and iron, and reduced for energy, carbohydrate, folate, vitamin B6 and 12. Children on egg supplementation had a much higher increase in vitamin A intake (142.0 μg) than the controls (49.8 μg) between pre-and post-intervention. Regarding the physical fitness markers, pre-intervention mean handgrip, forward jump and total fitness scores were all higher in the intervention group and similar for the 50-m run. Post-intervention, the difference was lost while the total fitness score increased rather among controls (p < 0.001). For the biochemical markers, both serum ferritin (mean difference in control = 18.2 μg/L versus intervention= 20.1 μg/L) and zinc (mean difference in control 14.4 μg/L versus intervention 69.4 μg/L) increased more in the intervention than the controls. BMI-for-age z-score did not change between the intervention and control (p = 0.894) post-intervention, while the total cognition score improves slightly more in controls (4.8 points, p < 0.001) than in the intervention group (3.3 points, p < 0.001). ConclusionsThe results indicate that school children who consumed boiled eggs three times per week for three months had a higher mean intake of energy, carbohydrate, protein, iron, zinc, folate, and vitamins A and B6. The mean serum ferritin and albumin levels improved significantly higher in the experimental group. Egg supplementation did not significantly improve physical fitness and cognitive test scores of school-aged children. From this study, egg supplementation may improve some nutrients among school children but effects on congintion and physical fitness may require further study.

Explaining disparities in cognitive functioning: a test of competing hypotheses.

This study seeks to examine how the trajectories of total cognition scores exhibited by two birth cohorts vary by race/ethnicity, gender and the level of education. The empirical work of this study is be based on the 1998-2014 Health and Retirement Study (HRS) and the HRS Cross-Wave Tracker file. The analysis is limited to individuals with available information on cognitive functioning, sex, race/ethnicity, wave, highest level of education, and the physical comorbidities associated with cognitive functioning (20,985 from the Traditionalist cohort and 11,077 from the Baby Boomer cohort). Growth curve modelling is used to assess the aims of this study. Findings reveal that the cumulative advantage (disadvantage), persistent inequality and age-as-leveller hypotheses explain heterogeneity in total cognition scores for different race/ethnicity-sex groups, race/ethnicity-education and education-sex groups. These findings suggest that the development of an integrated treatment and screening mechanisms for physical comorbidities and cognitive functioning, and for the design of preventive strategies with the purpose of slowing or avoiding cognitive decline and maintaining healthy cognitive function should have a particular focus on females, racial ethnic minorities and those with low education.