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Psychiatric symptoms are frequent in neurocognitive disorders and dementias. Psychotic symptoms, mainly hallucinations and delusions, may appear in up to 50% of cases, influencing morbidity and mortality. Genetic, neurobiological, and environmental factors are involved in their onset. We conducted a narrative review of primary articles developed in humans that analyzed the genetic and neurobiological basis of psychosis in dementias. Evidence suggests that there are genetic risk variants for presenting psychosis in dementia. How genetic variants are related to schizophrenia, dementia, and other neurodegenerative disorders is under discussion. Candidate gene studies have found and genetic variants are associated with psychosis in dementia while genome-wide association studies have shown variants located in y . Epigenetic studies are scarce but have detected differences in the methylome of people with dementia and psychosis. On the other hand, alterations of the cholinergic, serotonergic, dopaminergic, and gabaergic neurotransmitter systems and the excitatory-inhibitory balance have been described in dementia. From a functional and anatomical point of view, there are alterations in several regions, mainly in the frontal area and other sensory processing and integration areas. Finally, we describe the influence of cognitive alterations in the genesis and maintenance of delusions and discuss the phenomenological overlap with confabulations. Multiple genetic, neurobiological, structural, and cognitive factors influence the occurrence of delusions and hallucinations in persons with dementia. Further research is needed to understand the pathophysiology of psychosis in dementias. This approach would support the understanding of psychosis as a transdiagnostic entity., Competing Interests: The authors completed the ICMJE conflict of interest statement and declared that they received no funds for the completion of this article; they have no financial relationships with organizations that may have an interest in the published article in the last three years; and they have no other relationships or activities that may influence the publication of the article. Forms can be requested by contacting the responsible author or the Editorial Committee of the Journal., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Postoperative neurocognitive disorders (PND) are the most common neurological disorders following surgery and anaesthesia before and within 12 months after surgery, with a high prevalence in the geriatric population. PND can severely deteriorate the quality of life of patients, especially among the elderly, mainly manifested as memory loss, attention, decline and language comprehension disorders, mostly in elderly patients, with an incidence as high as 31%. Previous studies have also raised the possibility of accelerated cognitive decline and underlying neuropathological processes associated with diseases that affect cognitive performance (e.g. Alzheimer's dementia) for reasons related to anaesthesia and surgery. Currently, most research on PND has focused on various molecular pathways, especially in the geriatric population. The various hypotheses that have been proposed regarding the mechanisms imply peripheral neuroinflammation, oxidative stress, mitochondrial homeostasis, synaptic function, autophagy disorder, blood-brain barrier dysfunction, the microbiota-gut-brain axis and lack of neurotrophic support. However, the underlying pathogenesis and molecular mechanisms of PND have not yet been uncovered. Recent research has focused on mitochondrial homeostasis. In this paper, we present a review of various studies to better understand and characterize the mechanisms of associated cognitive dysfunction. As the biochemical basis of PND becomes more clearly defined, future treatments based on mitochondrial homeostasis modulation can prove to be very promising.

The pathophysiological regulatory mechanisms in postoperative neurocognitive disorders (PNCDs) are intricately complex. Currently, the pathogenesis of PNCDs has not been fully elucidated. The mechanism involved may include a variety of factors, such as neuroinflammation, oxidative stress, and neuroendocrine dysregulation. Research into the gut microbiota-induced regulations on brain functions is increasingly becoming a focal point of exploration. Emerging evidence has shown that intestinal bacteria may play an essential role in maintaining the homeostasis of various physiological systems and regulating disease occurrence. Recent studies have confirmed the association of the gut-brain axis with central nervous system diseases. However, the regulatory effects of this axis in the pathogenesis of PNCDs remain unclear. Therefore, this paper intends to review the bidirectional signaling and mechanism of the gut-brain axis in PNCDs, summarize the latest research progress, and discuss the possible mechanism of intestinal bacteria affecting nervous system diseases. This review is aimed at providing a scientific reference for predicting the clinical risk of PNCD patients and identifying early diagnostic markers and prevention targets., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: To examine the effectiveness of explicit task (ie, equal, motor or cognitive) prioritization during dual tasking (DT) in adults with neurologic and neurocognitive disorders (stroke, Parkinson disease [PD], multiple sclerosis, dementia, Alzheimer disease, and mild cognitive impairment)., Data Source: A systematic search in 4 databases (PubMed, Web of Science, Embase, and Cochrane Central) yielded 1138 unique studies published up to 2023., Study Selection: Forty-one experimental studies were selected that assessed the effect of explicit prioritization instructions on both motor and cognitive performance during dual-tasks related to standing and walking in selected populations. Primary outcome measures were walking speed and response accuracy. Availability of data allowed us to perform a meta-analysis on 27 of the 41 articles by using inverse variance with a random effects model., Data Extraction: The data including design, subject characteristics, motor and cognitive tasks, prioritization, motor and cognitive outcomes, instructions, and key findings were extracted. Two assessors rated the selected studies for risk of bias and quality using the Quality Assessment Tools of the National Institutes of Health., Data Synthesis: This study examined 1535 adults who were asked to perform motor-cognitive DT in standing or walking, including 381 adults with stroke, 526 with PD, 617 with multiple sclerosis, 10 with dementia, 9 with Alzheimer disease, and 8 with mild cognitive impairment. During all prioritization instructions, participants slowed down during DT (standardized mean difference (SMD) equal =0.43; SMD motor =0.78; SMD cognitive =0.69, P<.03) while maintaining similar response accuracy (SMD equal =0.12; SMD motor =0.23; SMD cognitive =-.01, P>.05). However, considerable between-group heterogeneity was observed resulting in different motor and cognitive responses between pathologies., Conclusion: Motor prioritization was achieved in adults with PD and stroke, unlike adults with neurocognitive disorders who were negatively affected by any type DT prioritizing. The reported within-group heterogeneity revealed that effects of explicit task prioritization are dependent on motor and cognitive task complexity, and the type of instructions. Recommendations are provided to ensure accurate use of instructions during DT paradigms., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Understanding the nature and extent of sensorimotor decline in aging individuals and those with neurocognitive disorders (NCD), such as Alzheimer's disease, is essential for designing effective music-based interventions. Our understanding of rhythmic functions remains incomplete, particularly in how aging and NCD affect sensorimotor synchronization and adaptation to tempo changes., Objective: This study aimed to investigate how aging and NCD severity impact tapping to metronomes and music, with and without tempo changes., Methods: Patients from a memory clinic participated in a tapping task, synchronizing with metronomic and musical sequences, some of which contained sudden tempo changes. After exclusions, 51 patients were included in the final analysis., Results: Participants' Mini-Mental State Examination scores were associated with tapping consistency. Additionally, age negatively influenced consistency when synchronizing with a musical beat, whereas consistency remained stable across age when tapping with a metronome., Conclusions: The results indicate that the initial decline of attention and working memory with age may impact perception and synchronization to a musical beat, whereas progressive NCD-related cognitive decline results in more widespread sensorimotor decline, affecting tapping irrespective of audio type. These findings underline the importance of customizing rhythm-based interventions to the needs of older adults and individuals with NCD, taking into consideration their cognitive as well as their rhythmic aptitudes.

Event-related potentials (ERPs) are a common approach for investigating the neural basis of cognition and disease. There exists a vast and growing literature of ERP-related articles, the scale of which motivates the need for efficient and systematic meta-analytic approaches for characterizing this research. Here we present an automated text-mining approach as a form of meta-analysis to examine the relationships between ERP terms, cognitive domains and clinical disorders. We curated dictionaries of terms, collected articles of interest, and measured co-occurrence probabilities in published articles between ERP components and cognitive and disorder terms. Collectively, this literature dataset allows for creating data-driven profiles for each ERP, examining key associations of each component, and comparing the similarity across components, ultimately allowing for characterizing patterns and associations between topics and components. Additionally, by examining large literature collections, novel analyses can be done, such as examining how ERPs of different latencies relate to different cognitive associations. This openly available dataset and project can be used both as a pedagogical tool, and as a method of inquiry into the previously hidden structure of the existing literature. This project also motivates the need for consistency in naming, and for developing a clear ontology of electrophysiological components., (© 2022. The Author(s).)

HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy (cART), affecting 52% of people living with HIV. Our laboratory has demonstrated increased expression of cathepsin B (CATB) in postmortem brain tissue with HAND. Increased secretion of CATB from in vitro HIV-infected monocyte-derived macrophages (MDM) induces neurotoxicity. Activation of cannabinoid receptor type 2 (CB2R) inhibits HIV-1 replication in macrophages and the neurotoxicity induced by viral proteins. However, it is unknown if CB2R agonists affect CATB secretion and neurotoxicity in HIV-infected MDM. We hypothesized that HIV-infected MDM exposed to CB2R agonists decrease CATB secretion and neurotoxicity. Primary MDM were inoculated with HIV-1 ADA and treated with selective CB2R agonists JWH-133 and HU-308. HIV-1 p24 and CATB levels were determined from supernatants using ELISA. MDM were pre-treated with a selective CB2R antagonist SR144528 before JWH-133 treatment to determine if CB2R activation is responsible for the effects. Neuronal apoptosis was assessed using a TUNEL assay. Results show that both agonists reduce HIV-1 replication and CATB secretion from MDM in a time and dose-dependent manner and that CB2R activation is responsible for these effects. Finally, JWH-133 decreased HIV/MDM-CATB induced neuronal apoptosis. Our results suggest that agonists of CB2R represent a potential therapeutic strategy against HIV/MDM-induced neurotoxicity., (© 2022. The Author(s).)

Purpose: Impaired neurocognitive function (NCF) is extremely common in patients with higher grade primary brain tumor. We previously reported evidence of genetic variants associated with NCF in glioma patients prior to treatment. However, little is known about the effect of genetic variants on NCF decline after adjuvant therapy., Methods: Patients (N = 102) completed longitudinal NCF assessments that included measures of verbal memory, processing speed, and executive function. Testing was conducted in the postoperative period with an average follow up interval of 1.3 years. We examined polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase)., Results: Five polymorphisms were associated with longitudinal changes in processing speed and 14 polymorphisms with executive function. Change in processing speed was strongly associated with MCPH1 rs17631450 (P = 2.2 × 10 -7 ) and CCDC26 rs7005206 (P = 9.3 × 10 -7 ) in the telomerase pathway; while change in executive function was more strongly associated with FANCF rs1514084 (P = 2.9 × 10 -6 ) in the DNA repair pathway and DAOA rs12428572 (P = 2.4 × 10 -5 ) in the cognitive pathway. Joint effect analysis found significant genetic-dosage effects for longitudinal changes in processing speed (P trend  = 1.5 × 10 -10 ) and executive function (P trend  = 2.1 × 10 -11 ). In multivariable analyses, predictors of NCF decline included progressive disease, lower baseline NCF performance, and more at-risk genetic variants, after adjusting for age, sex, education, tumor location, histology, and disease progression., Conclusion: Our longitudinal analyses revealed that polymorphisms in telomerase, DNA repair, and cognitive pathways are independent predictors of decline in NCF in glioma patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Perioperative neurocognitive disorder (PND) is a postsurgical complication associated with neuroinflammation and impaired hippocampal neurogenesis, in which brain-derived neurotrophic factor (BDNF) plays a key role. Sarcopenia refers to age-related muscle loss that causes cognitive decline, muscle atrophy, and postoperative delirium. Rats with tail suspension (TS) were used to represent a low-activity model, which involves decreased hind limb function by TS. This hind limb unloading by TS can induce sarcopenia in 2 weeks. However, the relationship between PND and muscle atrophy is unclear. In this experiment, we investigated whether preoperative muscle atrophy induced by TS would affect neurogenesis and accelerate PND in rats., Methods: Sixty 21-week-old rats were assigned to 4 groups: the TS group, the TS with surgery (TS + S) group, the control group, and the control with surgery (control + S) group. After the abdominal manipulation under 3% sevoflurane anesthesia, cognitive function was assessed using the Morris water maze test and a fear-conditioning test. Neurogenesis was evaluated by checking BDNF secretion and immunohistochemical staining in the hippocampus., Results: The TS + S group showed impaired swimming latency (difference of means = 12.4 versus control + S; 95% confidence interval [CI], 2.0-22.7; P = .016) (difference of means = 15.2 versus TS; 95% CI, 0.4-30.1; P = .043) and path length (difference of means = 147.8 versus control + S; 95% CI, 20.7-274.9; P = .020) in the maze test and cued fear memory (difference of means = -26.0 versus TS; 95% CI, -46.4 to -5.6; P = .006) (difference of means = -22.3 versus control + S; 95% CI, -42.7 to -1.9; P = .026) in the fear-conditioning test. The postoperative levels of BDNF in the TS + S and TS groups were reduced compared with the other groups (P = .002). The number of neural precursors in the dentate gyrus was significantly lower in the TS + S group (P < .001)., Conclusions: We observed that preoperative hind limb muscle atrophy, indicated by TS, was associated with an increased occurrence of PND through the reduction in BDNF and neurogenesis after abdominal surgery in young adult rats. Therefore, we concluded that preoperative low skeletal muscle mass can induce PND due to impaired postoperative neurogenesis. Our findings might indicate that low-cost perioperative interventions, such as preoperative exercise, is beneficial to preventing PND., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

It has been estimated that 10-15% of people with Robinow syndrome (RS) show delayed development, but no studies have formally assessed developmental domains. The objective of this study is to provide the first description of cognitive, adaptive, and psychological functioning in RS. Thirteen participants (10 males) aged 4-51 years were seen for neuropsychological screening. Eight had autosomal-dominant RS (DVL1, n = 5; WNT5A, n = 3), four had autosomal-recessive RS (NXN, n = 2; ROR2, n = 2), and one had a mutation on an RS candidate gene (GPC4). Participants completed measures of intellectual, fine-motor, adaptive, executive, and psychological functioning. Findings indicated generally average intellectual functioning and low-average visuomotor skills. Adaptive functioning was average in autosomal-recessive RS (RRS) but low average in autosomal-dominant RS (DRS). Parent-report indicated executive dysfunction and attention problems in 4/8 children, 3/4 of whom had a DVL1 variant; adult self-report did not indicate similar difficulties. Learning disabilities were also reported in 4/8 individuals with DRS, 3/4 of whom had a DVL1 variant. Peer problems were reported for a majority of participants, many of whom also reported emotional concerns. Altogether, the findings indicate average neurocognitive functioning in RRS. In contrast, DRS, especially DVL1 pathogenic alleles, may confer specific risk for neurodevelopmental disability., (© 2020 Wiley Periodicals LLC.)

49,XXXXY was previously associated with profound to severe intellectual deficits. However, prior research papers on the cognitive profiles of this population were confounded by small samples sizes, wide age spreads, and incomplete histories of testosterone replacement therapy. This study is the first comprehensive, international investigation of the neurocognitive aspects of 49,XXXXY, and the potential effects of biological treatment on this profile. Sixty-seven boys from infancy to 11 years of age were enrolled in this longitudinal study, with the majority of boys postnatally diagnosed though chromosomal analysis. These boys received a comprehensive neurocognitive evaluation tailored to specific language-based deficits and cognitive challenges. Results revealed higher neurocognitive capacities, both verbally and nonverbally, than previously reported in this disorder. Infant boys with 49,XXXXY who received early hormonal therapy (EHT) had significantly higher scores on the cognitive domain of the Bayley Scales of Infant Development than untreated infants (p = .013). In addition, treated school-aged participants had significantly better scaled scores than untreated boys in form completion (p = .042), a task that requires deductive reasoning, on nonverbal testing on the Leiter International Performance Scales. This study indicates greater cognitive capacities with a wide range of abilities in the child with 49,XXXXY, thus warranting further investigation to identify and understand the critical influences on the etiology and the variability of those capacities., (© 2020 Wiley Periodicals LLC.)

Objectives: To compare differential expression protein in hippocampal tissues from mice of perioperative neurocognitive disorder (PND) and normal control mice and to explore the possible mechanism of PND., Methods: Mice were randomly divided into a PND group (n = 9) and a control group (n = 9).The mice in the PND group were treated with open tibial fracture with intramedullary fixation under isoflurane anesthesia, while the mice in the control group received pure oxygen without surgery. The cognitive functions of the two groups were examined using Morris water maze experiment, Open field test and Fear conditioning test. The protein expression of the hippocampus of mice was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the principal functions of dysregulated proteins., Results: A total of 21 proteins were differentially expressed between PND and control mice on days 1, 3, and 7 after the operation. These proteins were involved in many pathological processes, such as neuroinflammatory responses, mitochondrial oxidative stress, impaired synaptic plasticity, and neuronal cell apoptosis. Also, the dysregulated proteins were involved in MAPK, AMPK, and ErbB signaling pathways., Conclusion: The occurrence of PND could be attributed to multiple mechanisms., (© 2021. The Author(s).)

The neurovascular units (NVU) are the minimal functional units of the blood-brain barrier (BBB), composed of endothelial cells, pericytes, astrocytes, microglia, neurons, and the basement membrane. The BBB serves as an important interface for immune communication between the brain and peripheral circulation. Disruption of the NVU by the human immunodeficiency virus-1 (HIV-1) induces dysfunction of the BBB and triggers inflammatory responses, which can lead to the development of neurocognitive impairments collectively known as HIV-1-associated neurocognitive disorders (HAND). Methamphetamine (METH) use disorder is a frequent comorbidity among individuals infected with HIV-1. METH use may be associated not only with rapid HIV-1 disease progression but also with accelerated onset and increased severity of HAND. However, the molecular mechanisms of METH-induced neuronal injury and cognitive impairment in the context of HIV-1 infection are poorly understood. In this review, we summarize recent progress in the signaling pathways mediating synergistic impairment of the BBB and neuronal injury induced by METH and HIV-1, potentially accelerating the onset or severity of HAND in HIV-1-positive METH abusers. We also discuss potential therapies to limit neuroinflammation and NVU damage in HIV-1-infected METH abusers.

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.

Various research studies that have investigated the association between HIV infection and addiction underpin the role of various drugs of abuse in impairing immunological and non-immunological pathways of the host system, ultimately leading to augmentation of HIV infection and disease progression. These studies have included both in vitro and in vivo animal models wherein investigators have assessed the effects of various drugs on several disease parameters to decipher the impact of drugs on both HIV infection and progression of HIV-associated neurocognitive disorders (HAND). However, given the inherent limitations in the existing animal models of HAND, these investigations only recapitulated specific aspects of the disease but not the complex human syndrome. Despite the inability of HIV to infect rodents over the last 30 years, multiple strategies have been employed to develop several rodent models of HAND. While none of these models can accurately mimic the overall pathophysiology of HAND, they serve the purpose of modeling some unique aspects of HAND. This review provides an overview of various animal models used in the field and a careful evaluation of methodological strengths and limitations inherent in both the model systems and study designs to understand better how the various animal models complement one another., (Published by Elsevier B.V.)

Pregnancy is a complex state with many endocrinological challenges to a woman's physiology. Gestational Hypothyroidism (GHT) is an emerging condition where insufficiency of the thyroid gland has developed during pregnancy in a previously euthyroid woman. It is different to overt hypothyroidism, where marked elevation of thyroid-stimulating hormone with corresponding reduction in free thyroxine levels, is well known to cause detrimental effects to both the mother and the baby. During the past couple of decades, it has been shown that GHT is associated with multiple adverse maternal and fetal outcomes such as miscarriage, pre-eclampsia, placental abruption, fetal loss, premature delivery, neurocognitive and neurobehavioral development. However, three randomized controlled trials and a prospective cohort study performed within the last decade, show that there is no neurodevelopmental improvement in the offspring of mothers who received levothyroxine treatment for GHT. Thus, the benefit of initiating treatment for GHT is highly debated within the clinical community as there may also be risks associated with over-treatment. In addition, regulatory mechanisms that could possibly lead to GHT during pregnancy are not well elucidated. This review aims to unravel pregnancy induced physiological challenges that could provide basis for the development of GHT. During pregnancy, there is increased renal clearance of iodine leading to low iodine state. Also, an elevated estrogen level leading to an increase in circulating thyroglobulin level and a decrease in free thyroxine level. Moreover, placenta secretes compounds such as human chorionic gonadotropin (hCG), placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (s-Flt1) that could affect the thyroid function. In turn, the passage of thyroid hormones and iodine to the fetus is highly regulated within the placental barrier. Together, these mechanisms are hypothesized to contribute to the development of intolerance of thyroid function leading to GHT in a vulnerable individual., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mallawa Kankanamalage, Zhou and Li.)

Background: A pre-existing neurocognitive disorder (NCD) is a relevant factor for the outcome of surgical patients. To improve understanding of these conditions, we investigated the association between parameters of the cholinergic system and NCD., Method: This investigation is part of the BioCog project (www.biocog.eu), which is a prospective multicenter observational study including patients aged 65 years and older scheduled for elective surgery. Patients with a Mini-Mental State Examination (MMSE) score ≤23 points were excluded. Neurocognitive disorder was assessed according to the fifth Diagnostic and Statistical Manual of Mental Disorders criteria. The basal forebrain cholinergic system volume (BFCSV) was assessed with magnetic resonance imaging, the peripheral cholinesterase (ChE) activities with point-of-care measurements, and anticholinergic load by analyzing the long-term medication with anticholinergic scales (Anticholinergic Drug Scale [ADS], Anticholinergic Risk Scale [ARS], Anticholinergic Cognitive Burden Scale [ACBS]). The associations of BFCSV, ChE activities, and anticholinergic scales with NCD were studied with logistic regression analysis, adjusting for confounding factors., Results: A total of 797 participants (mean age 72 years, 42% females) were included. One hundred and eleven patients (13.9%) fulfilled criteria for mild NCD and 82 patients (10.3%) for major NCD criteria. We found that AcetylChE activity was associated with major NCD (odds ratio [95% confidence interval]: [U/gHB] 1.061 [1.010, 1.115]), as well as ADS score ([points] 1.353 [1.063, 1.723]) or ARS score, respectively ([points] 1.623 [1.100, 2.397]) with major NCD. However, we found no association between BFCSV or ButyrylChE activity with mild or major NCD., Conclusions: AcetylChE activity and anticholinergic load were associated with major NCD. Future research should focus on the association of the cholinergic system and the development of postoperative delirium and postoperative NCD., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Geriatric trauma patients will continue to increase in prevalence as the population ages, and many specific considerations need to be made to provide appropriate care to these patients. This article outlines common presentations of trauma in geriatric patients, with consideration to baseline physiologic function and patterns of injury that may be more prevalent in geriatric populations. Additionally, the article explores specific evidence-based management practices, the significance of trauma team and geriatrician involvement, and disposition decisions., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Schizophrenia (SCZ) and treatment-resistant schizophrenia (TRS) are associated with aberrations in immune-inflammatory pathways. Increased high mobility group protein 1 (HMGB1), an inflammatory mediator, and Dickkopf-related protein (DKK1), a Wnt/β-catenin signaling antagonist, affect the blood-brain barrier and induce neurotoxic effects and neurocognitive deficits., Aim: The present study aims to examine HMGB1 and DDK1 in nonresponders to treatments (NRTT) with antipsychotics (n = 60), partial RTT (PRTT, n = 55), and healthy controls (n = 43) in relation to established markers of SCZ, including interleukin (IL)-6, IL-10, and CCL11 (eotaxin), and to delineate whether these proteins are associated with the SCZ symptom subdomains and neurocognitive impairments., Results: HMGB1, DKK1, IL-6, and CCL11 were significantly higher in SCZ patients than in controls. DKK1 and IL-6 were significantly higher in NRTT than in PRTT and controls, while IL-10 was higher in NRTT than in controls. Binary logistic regression analysis showed that SCZ was best predicted by increased DDK1 and HMGB1, while NRTT (vs PRTT) was best predicted by increased IL-6 and CCL11 levels. A large part of the variance in psychosis, hostility, excitation, mannerism, and negative (PHEMN) symptoms and formal thought disorders was explained by HMGB1, IL-6, and CCL11, while most neurocognitive functions were predicted by HMGB1, DDK1, and CCL11., Conclusions: The neurotoxic effects of HMGB1, DKK1, IL-6, and CCL11 including the effects on the blood-brain barrier and the Wnt/β-catenin signaling pathway may cause impairments in executive functions and working, episodic, and semantic memory and explain, in part, PHEMN symptoms and a nonresponse to treatment with antipsychotic drugs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

HIV-related neurocognitive impairment (NCI) may increase the risk of death. However, a survival disadvantage for patients with NCI has not been well studied in the post-combination antiretroviral therapy (cART) era. Specifically, limited research has been conducted considering the reversible nature and variable progression of the impairment and this area demands further evaluation. We performed multivariable Cox proportional hazards modeling to assess the association between baseline NCI (global T scores) and mortality. A joint modeling approach was then used to model the trajectory of global neurocognitive functioning over time and the association between neurocognitive trajectory and mortality. Among the National NeuroAIDS Tissue Consortium's (NNTC) HIV-infected participants, we found a strong negative association between NCI and mortality in the older age groups (e.g., at age = 55, HR = 0.79; 95% CI 0.64-0.99). Three neurocognitive sub-domains (abstraction and executive functioning, speed of information processing, and motor) had the strongest negative association with mortality. Joint modelling indicated a 33% lower hazard for every 10-unit increase in global T scores (HR = 0.67; 95% CI 0.56-0.80). The study identified older HIV-infected individuals with NCI as a group needing special attention for the longevity of life. The study has considerable prognostic utility by not only predicting mortality hazard, but also future cognitive status.

Background: Reversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum, emerging related to encephalitis, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Among RESLES, mild encephalitis/encephalopathy with reversible splenial lesion (MERS) has been defined as a distinct clinicoradiologic syndrome associated with viral infections., Case Presentation: We report two children with multisystem inflammatory syndrome-children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who developed RESLES during the disease course. Encephalopathy was the main central nervous system symptom. Both of the children showed a rapid recovery, and brain magnetic resonance imaging revealed complete resolution of the splenial lesion within 1 week., Conclusion: The complete resolution of the splenial lesion and rapid recovery from encephalopathy in RESLES associated with SARS CoV-2 were similar to observed in MERS., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Aims: In patients with a history of chronic alcohol abuse, neurocognitive disorders (NCD) are not uncommon. The current study aimed to explore the course of cognitive performance, as measured by the Montreal Cognitive Assessment (MoCA), and everyday cognitive functioning, as measured by the Patient Competency Rating Scale (PCRS), in a large group of patients with alcohol use disorder (AUD) admitted to the Center of Excellence for Korsakov and Alcohol-related Cognitive Impairments., Methods: A multiple time-series design was used, in which the MoCA was administered at three time points of assessment, and the PCRS was completed by both the patient and a clinician at two time points, all during clinical treatment., Results: A total of 524 patients were included, 71 of whom were diagnosed with AUD only, 284 with AUD and mild NCD (ARCI) and 169 with AUD, major NCD and fulfilling criteria for Korsakoff's syndrome (KS)., Conclusions: Cognitive performance improved for all three groups during treatment, sustained abstinence and recovery from AUD. A low memory performance on the MoCA without improvement over time was predictive for KS, while improvement on this domain did not differentiate between AUD and ARCI. Changes in overall cognitive performance and orientation in patients with KS were positively related to changes in everyday cognitive functioning., (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press.)

Background: Subarachnoid hemorrhage (SAH) results in neurocognitive dysfunction and anxiety in humans and in animal models. Neurobehavioral tests such as the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests are validated in several models of SAH but have not been tested in the murine cisternal blood injection SAH model., Methods: Adult C57BL/6 mice (n=16) were randomized into two groups. Group 1 (n=8) received sham surgery. Group 2 (n=8) underwent SAH with 60 µL of autologous blood injected into the cisterna magna. Mice were then tested using the Modified Garcia Score on post-operative day 2 (POD2), EPM on POD5 & POD16, and MWM on POD6-16.Brain tissues harvested on POD16 were stained with Fluoro-Jade C to identify neurodegeneration in the hippocampus and cortex and Iba-1 immunofluorescence staining for microglial activation in the dentate gyrus and CA1 region of the hippocampus., Results: SAH mice showed increased escape latency on POD10. Swim distance was significantly increased on POD9-10 and swim speed was significantly decreased on POD6&POD10 in SAH mice. SAH mice exhibited a trend for lowered proportion of covered arm entries in EPM on POD16. Modified Garcia Score was not significantly different between the groups on POD2. The area of microglial activation in the dentate gyrus and CA1 region of the hippocampus was mildly increased but not significantly different at day 16 after SAH. Similarly, no significant differences were noted in the number of Fluoro-Jade C (+) cells in cortex or hippocampus., Conclusions: Cisternal single blood injection in mice produces mild neurocognitive deficits most pronounced in spatial learning and most evident 10 days after SAH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to investigate clinical neurocognitive performance and microstructural white matter (WM) alterations in infants of mothers with gestational diabetes mellitus (GDM) using diffusion tensor imaging., Materials and Methods: Infants (corrected gestational age, 33.42-36.00 weeks) of mothers with GDM (n = 31) and gestational age- and sex-matched unexposed controls (n = 31) accomplished 3-T diffusion tensor imaging scans and neurocognitive tests. Diffusion tensor imaging measures, mainly referring to fractional anisotropy (FA) values, were compared between 2 groups, and within-group analysis of correlation between FA values and neurocognitive testing outcomes in GDM-exposed infants was conducted subsequently., Results: Fractional anisotropy was significantly decreased in the splenium of corpus callosum, posterior limb of internal capsule, thalamus in infants of mothers with GDM when compared with controls (P < 0.05), reflecting microstructural WM abnormalities in the GDM group. Decreased FA was associated with worse neurocognitive performance in the exposed group (P < 0.05)., Conclusions: Individuals of mothers with GDM showed microstructural WM abnormalities in different brain regions, which were significantly related to worse neurocognitive performance. This might reveal that GDM directly insults the brain development of the offspring.

Background: High rates of cerebrovascular disease (CVD) have previously been described in pediatric human immunodeficiency virus (HIV). However, little is known about pediatric CVD in the era of antiretroviral therapy or about the contribution of CVD to HIV-associated neurocognitive disorders., Methods: We completed a neuroimaging substudy of the HIV-Associated Neurocognitive Disorders in Zambia study, a prospective cohort study of neurocognitive complications of pediatric HIV. Brain magnetic resonance imaging (1.5 T) was acquired for 34 HIV+ children on antiretroviral therapy and 17 HIV-exposed uninfected children (aged eight to 17 years). Demographics, medical history, neurological examination, and neuropsychologic testing results were collected. Two neuroradiologists, unaware of HIV status and clinical course, read the scans., Results: CVD was identified in seven of 34 children with HIV (HIV+ CVD+) and no HIV-exposed uninfected children (21% vs 0%, P = 0.05). Three participants had white matter changes suggestive of small vessel disease, four had infarcts, and two had evidence of intracranial artery stenosis. Age of antiretroviral therapy initiation and exposure to protease inhibitors or efavirenz was not significantly different between children with and without CVD. HIV+ CVD+ children had significantly worse scores on a summary measure of cognition than the HIV+ CVD- group (NPZ8 score -0.57 vs 0.33, P = 0.04)., Conclusions: This study demonstrates high rates of CVD in children with HIV despite antiretroviral therapy, and worse cognitive performance in children with CVD. Longitudinal studies are necessary to determine the mechanisms and incidence of new-onset CVD in children with HIV., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background Neurocognitive impairment is a common complication of congenital heart disease (CHD) as well as acquired cardiovascular disease. Data are limited on neurocognitive function in adults with CHD (ACHD). Methods and Results A total of 1020 individuals with mild-to-moderate ACHD and 497 987 individuals without ACHD from the volunteer-based UK Biobank study underwent neurocognitive tests for fluid intelligence, reaction time, numeric memory, symbol-digit substitution, and trail making at enrollment and follow-up. Performance scores were compared before and after exclusion of preexisting stroke or coronary artery disease as measures of cerebro- and cardiovascular disease. Individuals with ACHD had significantly poorer performance on alpha-numeric trail making, a measure of visual attention and cognitive flexibility, spending 6.4 seconds longer on alpha-numeric trail making (95% CI, 3.0-9.9 seconds, P =0.002) and 2.5 seconds longer on numeric trail making (95% CI, 0.5-4.6 seconds, P =0.034), a measure of visual attention and processing speed. The ACHD cohort had modestly lower performance on symbol-digit substitution, a measure of processing speed, with 0.9 fewer correct substitutions (95% CI, - 1.5 to - 0.2 substitutions, P =0.021). After excluding preexisting stroke or coronary artery disease, individuals with ACHD continued to show poorer performance in all 6 domains ( P =NS). Conclusions Individuals with mild-to-moderate ACHD had poorer neurocognitive performance, most significantly in tests of cognitive flexibility, analogous to deficits in children with CHD. These differences appear to be driven by increased burden of cerebro- and cardiovascular disease among individuals with ACHD.

Physical inactivity and a sedentary lifestyle are associated with a chronic low-level inflammatory state which has been implicated in the pathogenesis of cardiovascular disease. There is growing interest in exercise programs as part of surgical 'prehabilitation'. We therefore studied preoperative physical activity levels of patients undergoing elective Coronary Artery Bypass Graft (CABG) surgery, and performed an exploratory analysis of the influence of physical activity on postoperative outcome. The Short Questionnaire to Assess Health (SQUASH) was used to assess physical activity among 100 patients, of mean (SD) age 65.4 (7.6) years. Additionally, handgrip strength was measured, and the get-up-and-go test was conducted. Anxiety, depression, and quality of life were assessed, and a computerised cognitive test battery was used to assess cognitive performance preoperatively, and three months after surgery. Preoperatively, 76% of patients met the recommended national guidelines for physical activity. The incidence of pre-existing medical conditions, and other pre-operative patient features were similar in active and inactive patients. Preoperative physical activity was significantly inversely related to the logistic EuroSCORE. The level of physical activity was also significantly inversely related with preoperative C-reactive protein (CRP) and peak postoperative CRP, but physical activity did not appear to be associated with any adverse postoperative outcomes or extended length of hospital stay. The incidence of postoperative neurocognitive disorder (PNCD) at 3 months postoperatively was 26%. Cognitive performance was not related with physical activity levels. In summary, this was the first study to assess activity levels of cardiac surgical patients with the SQUASH questionnaire. The majority of patients were physically active. Although physical activity was associated with lower levels of inflammation in this pilot study, it was not associated with an improved clinical or cognitive postoperative outcome., Competing Interests: SRT, SWD, IT and RH have declared that no competing interests exist. SD has read the journal's policy and the authors of this manuscript have the following competing interests: grants from Stichting Beatrixoord Noord-Nederland during the conduct of the study. This grant is not related in anyway to the study; MAM has read the journal's policy and the authors of this manuscript have the following competing interests:consultancy from AtriCure, Getinge and LivaNova; ARA has read the journal's policy and the authors of this manuscript have the following competing interests: reports unrestricted research and/or consultancy for The Medicines Company, Janssen Pharma, Carefusion/BD, Orion Pharma, Ever Pharma, and Philips (all for work unrelated to the current study; all payments to institution); and being Editor of the British Journal of Anaesthesia. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Maternal diet plays a beneficial role in the health, including the neurodevelopment, of offspring. Insufficient fibre consumption among the general population has increased concern about neurocognitive diseases. However, the association between maternal low-fibre diet (MLFD) and neurocognitive function in offspring is still unclear., Methods: Mice were fed diets containing diverse levels of fibre or administered short-chain fatty acids (SCFAs) during gestation. The neurocognitive functions of the offspring and synaptic plasticity-related protein levels were measured. Gene expression was disrupted by siRNA interference. Samples from pregnant women and paired umbilical cord blood (UCB) samples were analysed by the general linear model., Results: We found that MLFD impaired cognitive function and synaptic plasticity in offspring and that the impairments were reversed by butyrate intake but not propionate intake. Mechanistic studies showed that histone deacetylase (HDAC)-4 is the most likely mediator of butyrate-dependent neurocognitive improvement. In addition, using human maternal serum and paired UCB samples, we demonstrated that SCFA levels in offspring were positively correlated with levels in the maternal serum., Conclusion: These results provide solid evidence that fibre in the maternal diet regulates neurocognitive functions in offspring through altering SCFA levels and supports the use of SCFA-dependent perinatal intervention for improving offspring health in the clinic., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: To explore the role of chemokine CC motif ligand 2 (CCL2) in spatial memory and cognition impairment, and the underlying mechanisms focused on inflammatory, glutamate metabolistic and apoptotic- associated mRNA expression., Materials and Methods: Stereotaxic surgery was performed here to establish a rat model by bilateral intra-hippocampal injection of CCL2. Morris water maze (MWM) and Novel object recognition test (NORT) were used to assess the learning, memory and cognitive ability respectively. RT-PCR was used to detect the relative mRNA expression of inflammatory, glutamate metabolistic and apoptotic- associated indexes. Nissl and TUNEL staining were performed to observe the morphological changes of hippocampal CA1 zone and quantified the apoptosis of hippocampal neurons of CA1 zones respectively., Key Findings: We found CCL2 injured cognitive function in rats. Six days after CCL2 injection, we revealed the following obvious mRNA expression changes: (1) increasing of the neuroinflammatory cytokines IL-1β, CXCL-10, IL-6; (2) decreasing of the glutamate transporters GLT-1 and GLAST and increasing of PAG; (3) increasing of the apoptotic genes caspase-8, caspase-3 and Bax, while decreasing the anti-apoptotic gene Bcl-2. Further, Nissl staining and TUNEL confirmed the injury of the structure of hippocampal CA1 zones and the apoptosis of hippocampal neurons., Significance: Our results indicated that CCL2 impaired spatial memory and cognition, the involving mechanisms may link to the up-regulation of mRNA expression of the three major pathological events: inflammation, excitotoxicity and neuronal apoptosis, which were involved in HIV-associated neurocognitive disorder (HAND). Taken together, these findings suggest a potential therapeutic strategy against CCL2., Competing Interests: Declaration of competing interest I would like to declare that no conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2020. Published by Elsevier Inc.)

With the aging of the world population, and improvements in medical and health technologies, there are increasing numbers of elderly patients undergoing anaesthesia and surgery. Perioperative neurocognitive dysfunction has gradually attracted increasing attention from academics. Very recently, 6 well-known journals jointly recommended that the term perioperative neurocognitive dysfunction (defined according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition) should be adopted to improve the quality and consistency of academic communications. Perioperative neurocognitive dysfunction currently includes preoperatively diagnosed cognitive decline, postoperative delirium, delayed neurocognitive recovery, and postoperative cognitive dysfunction. Increasing evidence shows that the gut microbiota plays a pivotal role in neuropsychiatric diseases, and in central nervous system functions via the microbiota-gut-brain axis. We recently reported that abnormalities in the composition of the gut microbiota might underlie the mechanisms of postoperative cognitive dysfunction and postoperative delirium, suggesting a critical role for the gut microbiota in perioperative neurocognitive dysfunction. This article therefore reviewed recent findings on the linkage between the gut microbiota and the underlying mechanisms of perioperative neurocognitive dysfunction.

Delayed neurocognitive recovery (DNR) is common in elderly patients after major noncardiac surgery. This study was designed to investigate the best statistical rule in diagnosing DNR with the Montreal cognitive assessment (MoCA) in elderly surgical patients.This was a cohort study. One hundred seventy-five elderly (60 years or over) patients who were scheduled to undergo major noncardiac surgery were enrolled. A battery of neuropsychological tests and the MoCA were employed to test cognitive function at the day before and on fifth day after surgery. Fifty-three age- and education-matched nonsurgical control subjects completed cognitive assessment with the same instruments at the same time interval. The definition of the international study of postoperative cognitive dysfunction (ISPOCD 1) was adopted as the standard reference for diagnosing DNR. With the MoCA, the following rules were used to diagnose DNR: the cut-off point of ≤26; the 1 standard deviation decline from baseline; the 2 scores decline from baseline; and the Z score of ≥1.96. The sensitivity and specificity as well as the area under receiver operating characteristic curve for the above rules in diagnosis of DNR were calculated.The incidence of DNR was 13.1% (23/175) according to the ISPOCD1 definition. When compared with the standard reference, the 2 scores rule showed the best combination of sensitivity (82.6%, 95% confidence interval [CI] 67.1%-98.1%) and specificity (82.2%, 95% CI 76.2%-88.3%); it also had the largest area under receiver operating characteristic curve (0.824, 95% CI 0.728-0.921, P < .001). The cut-off point rule showed high sensitivity (95.7%) and low specificity (37.5%), whereas the 1 standard deviation and the Z score rules showed low sensitivity (47.8% and 21.7%, respectively) and high specificity (93.4% and 97.3%, respectively).Compared with the ISPOCD1 definition, the 2 scores rule with MoCA had the best combination of sensitivity and specificity to diagnose DNR.

Introduction: The main aim of this study is to determine the prevalence of behavioural disturbances (BD) in a group of patients with diagnosis of neurocognitive disorders assessed by a memory clinic in a referral assessment centre in Bogotá, Colombia, in 2015., Material and Methods: This is an observational, retrospective descriptive study of 507 patients with a diagnosis of neurocognitive disorder (according to DSM-5 criteria) evaluated in a referral centre in Bogotá, Colombia, in 2015., Results: Among the group of patients assessed, analyses reveal mean age for minor neurocognitive disorders of 71.04 years, and 75.32 years for major neurocognitive disorder (P <0.001). A total of 62.72% of the sample were female. The most prevalent aetiology of the neurocognitive disorders was Alzheimer's disease, followed by behavioural variant frontotemporal dementia and neurocognitive disorders due to multiple aetiologies. BD occur more frequently in neurocognitive disorder due to behavioural variant frontotemporal dementia (100%), Alzheimer's disease (77.29%) and vascular disease (76.19%). The most prevalent BD in the group assessed were apathy (50.75%), irritability (48.45%), aggression (16.6%), and emotional lability (14.76%)., Conclusions: BD are highly prevalent in patients with diagnosis of major neurocognitive disorder. BD are more prevalent in behavioural variant frontotemporal dementia than any other group. Apathy, irritability, emotional lability and aggression are the BD that occur with greater prevalence in our sample. We discuss the importance of BD in the clinical progression of neurocognitive disorders., (Copyright © 2018 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The conflict monitoring system exerts an influence on centers responsible for cognitive control, causing them to intervene more strongly in processing when conflict occurs. These mechanisms are usually investigated through specific tasks where there is an inherent interference elicited by the congruency or incongruency between the stimuli and responses, such as the Stroop task. In studies of emotional conflict, one hypothesis related to the dorsal anterior cingulate cortex (ACC) is that it serves, in part, to signal the appearance of conflicts, thus triggering compensatory adjustments. This study aims to verify whether the conflict monitoring hypothesis is confirmed in a group with Alzheimer's disease and, therefore, whether they exhibit a reduction in their reaction times., Method: A group of healthy older adults (HOA) and a group with Major Neurocognitive Disorders due to probable AD were evaluated to test the conflict monitoring hypothesis with an emotional Stroop task., Results: A significant interaction was obtained on the word and faces blocks. In the HOA group, a reduction in reaction times was observed, whereas in the AD groups, no reduction in reaction times was obtained., Conclusions: Whereas in HOA the conflict monitoring hypothesis is confirmed, in the Major Neurocognitive Disorders due to probable AD group there is no reduction in their reaction times on the high conflict resolution trials (incongruent trials that follow incongruent trials) due to their difficulty in making compensatory adjustments to cognitive control that help them to reduce conflict and improve their success rate.

Introduction: The value of the P300 cognitive event-related potential in the diagnosis of Alzheimer subtype neurocognitive disorders is still incipient. Recent studies suggest that combining it with neuropsychological tests by cognitive domains would allow an objective and early characterisation of the cognitive impairment in its initial stages., Aims: To characterise the electrophysiological patterns in the P300 potential that obtain a discriminatory value for the diagnosis and classification of the neurocognitive disorders with a possible Alzheimer-type aetiology., Subjects and Methods: This study examines 39 patients classified, according to the DSM-5, with possible Alzheimer-type minor and major neurocognitive disorders, aged between 50 and 85 years, and 53 control subjects with normal cognitive functions. The P300 potential is registered in the auditory mode, oddball paradigm and centroparietal recording., Results: P300 latency is significantly prolonged in subjects with neurocognitive disorder; there are significant differences in the mean values and confidence intervals between healthy controls and patients. No significant differences are obtained in P300 latency between groups with minor and major neurocognitive disorder. The mean amplitude value decreases in neurocognitive disorder, and the P300 amplitude logarithm of the control groups and those with minor and major neurocognitive disorder reaches significantly different mean values and confidence intervals., Conclusions: The parameters quantified in the P300 potential can be used as complementary biomarkers to classify the presence and level of cognitive dysfunction with a possible Alzheimer-type aetiology.

Brain tumors are the most common solid tumor in childhood, and although survival outcomes continue to improve, survival is frequently offset by devastating late effects from tumor and treatment. The long-term effects of brain tumors and the therapy necessary to treat them range from sensory and neuroendocrine abnormalities to neurocognitive deficits leading to inferior quality of life. The multifactorial neurocognitive injury is one of the most broadly impacting and challenging late effects to predict and subsequently treat. Certain treatment modalities, such as intrathecal methotrexate and radiation, have been shown to be associated with poor neurocognition; however, long-term outcomes remain highly variable. There are efforts underway to investigate how to better predict, identify, and manage such neurocognitive injury in survivors of pediatric brain tumors. Herein, we focus on the current knowledge of neurocognitive outcomes and potential treatment strategies for this high-risk group., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Patients with sickle cell disease (SCD) are at increased risk for neurocognitive impairments. While disease-modifying treatment, such as hydroxycarbamide (hydroxyurea), may decrease this risk, it has not been systematically investigated in children with SCD. We screened neurocognitive functioning in 103 adolescents with SCD (16-17 years, 50% female) and compared outcomes between patients with a history of exposure to hydroxycarbamide (n = 12 HbSC/HbSβ + thalassaemia; n = 52 HbSS/HbSβ 0 thalassaemia) and those never treated with hydroxycarbamide (n = 31 HbSC/HbSβ + thalassaemia; n = 8 HbSS/HbSβ 0 thalassaemia). Demographic distributions were similar between the groups. After adjusting for socioeconomic status, the hydroxycarbamide group had significantly higher scores on nonverbal IQ (HbSC/HbSβ thalassaemia: P = 0·036, effect size [d] = 0·65), reaction speed (HbSS/HbSβ 0 thalassaemia: P = 0·002, d = 1·70), sustained attention (HbSS/HbSβ 0 thalassaemia: P = 0·014, d = 1·30), working memory (HbSC/HbSβ + thalassaemia: P = 0·034, d = 0·71) and verbal memory (HbSC/HbSβ + thalassaemia: P = 0·038, d = 0·84) when compared to those who did not receive hydroxycarbamide. In patients with HbSS/HbSβ 0 thalassaemia, longer treatment duration with hydroxycarbamide was associated with better verbal memory (P = 0·009) and reading (P = 0·002). Markers of hydroxycarbamide effect, including higher fetal haemoglobin (HbF), higher mean corpuscular volume (MCV) and lower white blood cell count (WBC), were associated with better verbal fluency (HbF: P = 0·014, MCV: P = 0·006, WBC: P = 0·047) and reading (MCV: P = 0·021, WBC: P = 0·037). Cognitive impairment may be mitigated by exposure to hydroxycarbamide in adolescents with SCD., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

A history of concussion has been associated with decreased neurocognitive function and postural control. The purpose of our study was to compare neurocognitive function and postural control in collegiate athletes with and without varying histories of concussion. Collegiate athletes were divided into groups based on 0 ( n  = 129), 1 ( n  = 91), 2 ( n  = 52), and 3+ ( n  = 34) prior concussions. Participants in each group were carefully matched by sport, sex, height, weight, and age. Athletes were administered the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT™) and the Sensory Organization Test (SOT) as part of a standard of care pre-season assessment. Group ImPACT (Verbal and Visual Memory, Visual Motor Speed, and Reaction Time) and SOT (Equilibrium Score and Somatosensory, Visual, and Vestibular sensory ratios) outcome scores were compared using one-way analyses of variance (ANOVAs). Coefficients of variation (CVs) were also calculated for each outcome score and were compared using two-sample tests with 95% confidence intervals (CIs). Participants with and without a history of concussion were not significantly different for any ImPACT or SOT outcome score ( p' s > 0.10). Groups (0, 1, 2, and 3+ previous concussions) were not different from each other for any ImPACT or SOT outcome score (p's ≥ 0.11). Likewise, the CVs associated with each ImPACT and SOT outcome score did not vary significantly between outcome scores for any group comparison ( p  ≥ 0.09). Our findings suggest that a history of one or more concussions does not influence neurocognitive performance or postural stability in collegiate athletes at their pre-season baseline assessment.

Background: Although the clinical outcomes continue to be scrutinized, there are a few data summarizing the changes in perfusion parameters in postoperative patients. The objective was to undertake a systematic literature review and perform a meta-analysis to assess the effects of cerebral perfusion changes in cognitive and functional status., Methods: A systematic search was conducted in July 2018 identifying articles comparing perfusion parameter changes before and after carotid revascularization in patients with carotid artery stenosis. Combined overall effect sizes were calculated using random-effects models., Results: The literature search identified 1031 unique articles eligible for analysis. Sixteen studies including 755 patients were identified. The studies were different for many methodological factors, for example, sample size, type of patients, statistical measure, type of test, timing of assessment, and so on. There were no differences in cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO 2 ), and relative cerebral blood volume (rCBV) between preintervention and postintervention, but there was a significant increase of cerebral blood flow (CBF) (95% confidence interval [CI] standardized mean difference [Std. MD] : -0.83 [-1.27, -0.40]; P = 0.0002; I 2  = 68%) and relative cerebral blood flow (rCBF) (95% CI Std. MD: -0.72 [-1.61, -0.27]; P < 0.0001; I 2  = 48%) after operation. In addition, the perfusion of mean transit time (MTT) (95% CI Std. MD: 1.26 [0.62, 1.90]; P = 0.0001; I 2  = 84%), oxygen extraction fraction (OEF) (95% CI Std. MD: 0.78 [0.24, 1.33]; P = 0.005; I 2  = 0%), time to peak (TTP) (95% CI Std. MD: 0.46 [0.16, 0.77]; P = 0.003; I 2  = 47%), and relative mean transit time (rMTT) (95% CI Std. MD: 0.41 [0.33, 0.50]; P < 0.00001; I 2  = 67%) was higher before than after operation., Conclusions: The increase in changes in CBF and rCBF and the decrease in MTT, OEF, TTP, and rMTT after operation may indicate the improvement of cognition in the short term. Intraoperative perfusion parameters could be an important adjuvant monitoring method in neurocognitive changes after carotid revascularization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Mechanical ventilation to alter and improve respiratory gases is a fundamental feature of critical care and intraoperative anesthesia management. The range of inspired O 2 and expired CO 2 during patient management can significantly deviate from values in the healthy awake state. It has long been appreciated that hyperoxia can have deleterious effects on organs, especially the lung and retina. Recent work shows intraoperative end-tidal (ET) CO 2 management influences the incidence of perioperative neurocognitive disorder (POND). The interaction of O 2 and CO 2 on cerebral blood flow (CBF) and oxygenation with alterations common in the critical care and operating room environments has not been well studied., Methods: We examine the effects of controlled alterations in both ET O 2 and CO 2 on cerebral blood flow (CBF) in awake adults using blood oxygenation level-dependent (BOLD) and pseudo-continuous arterial spin labeling (pCASL) MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO 2 and O 2 in various combinations commonly observed during anesthesia., Results: Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse brain voxel responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age suggesting greater risk., Conclusions: Human CBF responds dramatically to alterations in ET gas tensions commonly seen during anesthesia and in critical care. Such alterations may contribute to delirium following surgery and under certain circumstances in the critical care environment., Trial Registration: ClincialTrials.gov NCT02126215 for some components of the study. First registered April 29, 2014.

Despite the large body of data available, chronic cerebral hypoperfusion lacks an operative definition. In a tautological way, the term hypoperfusion is being referred to conditions of "inadequate blood flow", "defects of perfusion" or "dysfunction of autoregulation". The chronicity refers to sustained conditions or wavering states characterized by repeated phases of inefficient functional hyperemia. The phenomenon may affect the whole brain or defined areas. A few defined clinical disorders, including heart failure, hypotension, atherosclerosis of large or small vessels and carotid stenosis are thought to cause progressive brain disorders due to chronic hypoperfusion. The clinical relevance manifests mostly as neurocognitive disorders associated with neuroimaging changes.The available data support a conceptual framework that considerschronic cerebral hypoperfusiona likely, relevant pathogenic mechanism for the neurodegeneration-like progression of the neurocognitive disorders. The relationship between neuropathology, cerebral perfusion, and symptoms progression is, however, elusive for several aspects. Typical microangiopathy findings, such as MRI white matter hyperintensities, may appear in individuals without any cerebrovascular risk or vascular lesions. Pathology features of the MRI changes, such as demyelination and gliosis, may result from dysfunction of the neuro-vascular unit not directly associated withvascular mechanisms. In this review, we aim to overview the most common clinical conditions thought to reflect chronic hypoperfusion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The study objective was to determine whether targeted therapy to optimize cerebral oxygenation is associated with improved neurocognitive and perioperative outcomes., Methods: In a prospective trial, intraoperative cerebral oximetry monitoring using bilateral forehead probes was performed in cardiac surgical patients who were randomly assigned to an intervention group in which episodes of cerebral oxygen desaturation (<60% for >60 consecutive seconds at either probe) triggered an intervention protocol or a control group in which the cerebral oximetry data were hidden from the clinical team, and no intervention protocol was applied. Cognitive testing was performed preoperatively and at postoperative months 3 and 6; domains studied were response speed, processing speed, attention, and memory. Perioperative outcomes studied were death, hospital length of stay, intensive care unit length of stay, postoperative day of extubation, time on mechanical ventilation, intensive care unit delirium, Sequential Organ Failure Assessment on intensive care unit admission, and intensive care unit blood transfusion., Results: Group mean memory change scores were significantly better in the intervention group at 6 months (0.60 [standard error, 0.30] vs -0.17 [standard error, 0.33], adjusted P = .008). However, presence, duration, and severity of cerebral desaturation were not associated with cognitive change scores. Perioperative outcomes did not differ between the intervention and control groups., Conclusions: Targeted therapy to optimize cerebral oxygenation was associated with better memory outcome in a group of cardiac surgical patients. Some aspects of the protocol other than desaturation duration and severity contributed to the observed neuroprotective effect., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Symptom factors present during the first week following concussion may predict subsequent concussion outcomes and recovery duration. We hypothesized that a high loading on cognitive-fatigue-migraine and somatic factors would be predictive of neurocognitive impairment following concussion. We also hypothesized that the affective factor would be related to vestibular symptoms and impairment., Design: Prospective repeated measures., Setting: Concussion specialty clinic., Participants: Athletes aged 13 to 20 years diagnosed with a concussion within the past 7 days., Independent Variable: Symptom factors at the initial visit 1 to 7 days after injury., Main Outcome Measure: Symptom factor score, neurocognitive testing, and vestibular/ocular motor assessment at the second visit (2-4 weeks after injury)., Results: The somatic symptom factor from the initial visit was significant (P < 0.05) in all vestibular/ocular screening components (P < 0.05) but not neurocognitive test performance (P > 0.05) at the second visit. The cognitive-migraine-fatigue and affective symptom factors predicted symptom burden at the second visit (P < 0.001) but did not predict recovery time (P = 0.200)., Conclusions: The somatic symptom factor during the first week after injury predicted symptom provocation during vestibular/ocular screening at 2 to 4 weeks after injury. Specifically, higher scores on somatic symptom factor at the initial visit predicted worse symptom reporting for all vestibular/ocular screening components at the second visit. Patients with higher scores on the cognitive-migraine-fatigue and affective symptom factors at the initial visit predicted total symptom burden at the second visit.

Objective: Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV., Method: Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria., Results: When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure., Conclusions: The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.

Despite the reliability of intelligence measures in predicting important life outcomes such as educational achievement and mortality, the exact configuration and neural correlates of cognitive abilities remain poorly understood, especially in childhood and adolescence. Therefore, we sought to elucidate the factorial structure and neural substrates of child and adolescent intelligence using two cross-sectional, developmental samples (CALM: N = 551 (N = 165 imaging), age range: 5-18 years, NKI-Rockland: N = 337 (N = 65 imaging), age range: 6-18 years). In a preregistered analysis, we used structural equation modelling (SEM) to examine the neurocognitive architecture of individual differences in childhood and adolescent cognitive ability. In both samples, we found that cognitive ability in lower and typical-ability cohorts is best understood as two separable constructs, crystallized and fluid intelligence, which became more distinct across development, in line with the age differentiation hypothesis. Further analyses revealed that white matter microstructure, most prominently the superior longitudinal fasciculus, was strongly associated with crystallized (gc) and fluid (gf) abilities. Finally, we used SEM trees to demonstrate evidence for developmental reorganization of gc and gf and their white matter substrates such that the relationships among these factors dropped between 7-8 years before increasing around age 10. Together, our results suggest that shortly before puberty marks a pivotal phase of change in the neurocognitive architecture of intelligence., Competing Interests: Declarations of Competing Interest None., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)