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It has been more than three years since COVID-19 impacted the lives of millions of people, many of whom suffer from long-term effects known as long-haulers. Notwithstanding multiorgan complaints in long-haulers, signs and symptoms associated with cognitive characteristics commonly known as "brain fog" occur in COVID patients over 50, women, obesity, and asthma at excessive. Brain fog is a set of symptoms that include cognitive impairment, inability to concentrate and multitask, and short-term and long-term memory loss. Of course, brain fog contributes to high levels of anxiety and stress, necessitating an empathetic response to this group of COVID patients. Although the etiology of brain fog in COVID-19 is currently unknown, regarding the mechanisms of pathogenesis, the following hypotheses exist: activation of astrocytes and microglia to release pro-inflammatory cytokines, aggregation of tau protein, and COVID-19 entry in the brain can trigger an autoimmune reaction. There are currently no specific tests to detect brain fog or any specific cognitive rehabilitation methods. However, a healthy lifestyle can help reduce symptoms to some extent, and symptom-based clinical management is also well suited to minimize brain fog side effects in COVID-19 patients. Therefore, this review discusses mechanisms of SARS-CoV-2 pathogenesis that may contribute to brain fog, as well as some approaches to providing therapies that may help COVID-19 patients avoid annoying brain fog symptoms., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable Consent for Publication: Not applicable Competing Interests: The author declares no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This report describes persistent symptoms associated with post-acute COVID-19 syndrome (PACS) and the impact of these symptoms on physical function, cognitive function, health-related quality of life, and participation., Design: This study used a cross-sectional observational study design. Patients attending Mount Sinai's post-acute COVID-19 syndrome clinic completed surveys containing patient-reported outcomes., Results: A total of 156 patients completed the survey, at a median (range) time of 351 days (82-457 days) after COVID-19 infection. All patients were prevaccination. The most common persistent symptoms reported were fatigue (n = 128, 82%), brain fog (n = 105, 67%), and headache (n = 94, 60%). The most common triggers of symptom exacerbation were physical exertion (n = 134, 86%), stress (n = 107, 69%), and dehydration (n = 77, 49%). Increased levels of fatigue (Fatigue Severity Scale) and dyspnea (Medical Research Council) were reported, alongside reductions in levels of regularly completed physical activity. Ninety-eight patients (63%) scored for at least mild cognitive impairment (Neuro-Qol), and the domain of the EuroQol: 5 dimension, 5 level most impacted was Self-care, Anxiety/Depression and Usual Activities., Conclusions: Persistent symptoms associated with post-acute COVID-19 syndrome seem to impact physical and cognitive function, health-related quality of life, and participation in society. More research is needed to further clarify the relationship between COVID-19 infection and post-acute COVID-19 syndrome symptoms, the underlying mechanisms, and treatment options., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Chronic neurodegenerative diseases are complex, and their pathogenesis is uncertain. Alzheimer's disease (AD) is a neurodegenerative brain alteration that is responsible for most dementia cases in the elderly. AD etiology is still uncertain; however, chronic neuroinflammation is a constant component of brain pathology. Infections have been associated with several neurological diseases and viruses of the Herpes family appear to be a probable cause of AD neurodegenerative alterations. Several different factors may contribute to the AD clinical progression. Exogeneous viruses or other microbes and environmental pollutants may directly induce neurodegeneration by activating brain inflammation. In this paper, we suggest that exogeneous brain insults may also activate retrotransposons and silent human endogenous retroviruses (HERVs). The initial inflammation of small brain areas induced by virus infections or other brain insults may activate HERV dis-regulation that contributes to neurodegenerative mechanisms. Chronic HERV activation in turn may cause progressive neurodegeneration that thereafter merges in cognitive impairment and dementia in genetically susceptible people. Specific treatment for exogenous end endogenous pathogens and decreasing pollutant exposure may show beneficial effect in early intervention protocol to prevent the progression of cognitive deterioration in the elderly.

HIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective treatment options. Neurotrophin based therapies have excellent potential to stabilize and repair the nervous system. A novel non-peptide ligand, LM11A-31, that targets the p75 neurotrophin receptor (p75 NTR ) has been identified as a small bioavailable molecule capable of strong neuroprotection with minimal side effects. To evaluate the neuroprotective effects of LM11A-31 in a natural infection model, we treated cats chronically infected with feline immunodeficiency virus (FIV) with 13 mg/kg LM11A-31 twice daily over a period of 10 weeks and assessed effects on cognitive functions, open field behaviors, activity, sensory thresholds, plasma FIV, cerebrospinal fluid (CSF) FIV, peripheral blood mononuclear cell provirus, CD4 and CD8 cell counts and general physiology. Between 12 and 18 months post-inoculation, cats began to show signs of neural dysfunction in T maze testing and novel object recognition, which were prevented by LM11A-31 treatment. Anxiety-like behavior was reduced in the open field and no changes were seen in sensory thresholds. Systemic FIV titers were unaffected but treated cats exhibited a log drop in CSF FIV titers. No significant adverse effects were observed under all conditions. The data indicate that LM11A-31 is likely to be a potent adjunctive treatment for the control of neurodegeneration in HIV infected individuals.

Introduction: COVID-19 complications can include neurological, psychiatric, psychological, and psychosocial impairments. Little is known on the consequences of SARS-COV-2 on cognitive functions of patients in the sub-acute phase of the disease. We aimed to investigate the impact of COVID-19 on cognitive functions of patients admitted to the COVID-19 Rehabilitation Unit of the San Raffaele Hospital (Milan, Italy)., Material and Methods: 87 patients admitted to the COVID-19 Rehabilitation Unit from March 27th to June 20th 2020 were included. Patients underwent Mini Mental State Evaluation (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Rating Scale for Depression, and Functional Independence Measure (FIM). Data were divided in 4 groups according to the respiratory assistance in the acute phase: Group1 (orotracheal intubation), Group2 (non-invasive ventilation using Biphasic Positive Airway Pressure), Group3 (Venturi Masks), Group4 (no oxygen therapy). Follow-ups were performed at one month after home-discharge., Results: Out of the 87 patients (62 Male, mean age 67.23 ± 12.89 years), 80% had neuropsychological deficits (MoCA and MMSE) and 40% showed mild-to-moderate depression. Group1 had higher scores than Group3 for visuospatial/executive functions (p = 0.016), naming (p = 0.024), short- and long-term memory (p = 0.010, p = 0.005), abstraction (p = 0.024), and orientation (p = 0.034). Group1 was younger than Groups2 and 3. Cognitive impairments correlated with patients' age. Only 18 patients presented with anosmia. Their data did not differ from the other patients. FIM (<100) did not differ between groups. Patients partly recovered at one-month follow-up and 43% showed signs of post-traumatic stress disorder., Conclusion: Patients with severe functional impairments had important cognitive and emotional deficits which might have been influenced by the choice of ventilatory therapy, but mostly appeared to be related to aging, independently of FIM scores. These findings should be integrated for correct neuropsychiatric assistance of COVID-19 patients in the subacute phase of the disease, and show the need for long-term psychological support and treatment of post-COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist.

In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.

Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals' quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n = 11), with or without CD8+ lymphocyte depletion, based on detectable (n = 6) or non-detectable (n = 5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction. Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology.

COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence of central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It is unclear how much of the ischaemic damage is mediated by direct or inflammatory effects of virus on the CNS vasculature and how much is secondary to extracranial cardiorespiratory disease. Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted. Several aspects of COVID-19 are likely to impact on cognition. Cerebral white matter is particularly vulnerable to ischaemic damage in COVID-19 and is also critically important for cognitive function. There is accumulating evidence that cerebral hypoperfusion accelerates amyloid-β (Aβ) accumulation and is linked to tau and TDP-43 pathology, and by inducing phosphorylation of α-synuclein at serine-129, ischaemia may also increase the risk of development of Lewy body disease. Current therapies for COVID-19 are understandably focused on supporting respiratory function, preventing thrombosis and reducing immune activation. Since angiotensin-converting enzyme (ACE)-2 is a receptor for SARS-CoV-2, and ACE inhibitors and angiotensin receptor blockers are predicted to increase ACE-2 expression, it was initially feared that their use might exacerbate COVID-19. Recent meta-analyses have instead suggested that these medications are protective. This is perhaps because SARS-CoV-2 entry may deplete ACE-2, tipping the balance towards angiotensin II-ACE-1-mediated classical RAS activation: exacerbating hypoperfusion and promoting inflammation. It may be relevant that APOE ε4 individuals, who seem to be at increased risk of COVID-19, also have lowest ACE-2 activity. COVID-19 is likely to leave an unexpected legacy of long-term neurological complications in a significant number of survivors. Cognitive follow-up of COVID-19 patients will be important, especially in patients who develop cerebrovascular and neurological complications during the acute illness.

Arthropod-borne viruses or arbovirus, are most commonly associated with acute infections, resulting on various symptoms ranging from mild fever to more severe disorders such as hemorrhagic fever. Moreover, some arboviral infections can be associated with important neuroinflammation that can trigger neurological disorders including encephalitis, paralysis, ophthalmological impairments, or developmental defects, which in some cases, can lead to long-term defects of the central nervous system (CNS). This is well illustrated in Zika virus-associated congenital brain malformations but also in West Nile virus-induced synaptic dysfunctions that can last well beyond infection and lead to cognitive deficits. Here, we summarize clinical and mechanistic data reporting on cognitive disturbances triggered by arboviral infections, which may highlight growing public health issues spanning the five continents.

The impact of coronavirus disease 2019 (COVID-19) on clinical features of Parkinson's disease (PD) has been poorly characterized so far. Of 141 PD patients resident in Lombardy, we found 12 COVID-19 cases (8.5%), whose mean age and disease duration (65.5 and 6.3 years, respectively) were similar to controls. Changes in clinical features in the period January 2020 to April 2020 were compared with those of 36 PD controls matched for sex, age, and disease duration using the clinical impression of severity index for PD, the Movement Disorders Society Unified PD Rating Scale Parts II and IV, and the nonmotor symptoms scale. Motor and nonmotor symptoms significantly worsened in the COVID-19 group, requiring therapy adjustment in one third of cases. Clinical deterioration was explained by both infection-related mechanisms and impaired pharmacokinetics of dopaminergic therapy. Urinary issues and fatigue were the most prominent nonmotor issues. Cognitive functions were marginally involved, whereas none experienced autonomic failure. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Background: Human Immunodeficiency Virus (HIV) infection causes a myriad of neurological complications including cognitive deficits referred to as HIV-Associated Neurocognitive Disorders (HAND). With the introduction of combination antiretroviral therapy, there has been an epidemiological shift in cognitive disorders with a decline in the more severe HIV-Associated Dementia (HAD) to an increase in the less severe HAND: Asymptomatic Neurocognitive Impairment (ANI) and HIV-associated Mild Neurocognitive Disorder (MND). Central Nervous System (CNS) involvement in HIV interferes with cognitively demanding activities of daily living and hence a worse quality of life. Early diagnosis is delayed until symptoms are overt., Methods: We conducted a cross sectional analytical study of HIV infected persons on antiretroviral therapy attending HIV clinic. A systematic random sampling was done to select 360 patients. An interviewer administered structured questionnaire was used to collect socio-demographic data while the CD4 count and viral load were retrieved from the Academic Model Providing Access to Healthcare (AMPATH) database. Pearson's Chi Square test was used to compare proportions while independent sample t- test was used to compare continuous variables between the patients diagnosed with HAND and those without HAND. Logistic regression model was used to assess the factors associated with HAND., Results: The mean age of the study participants was 40.2 years. The overall prevalence of HAND was (81.1%) N = 292. Mild HAND (ANI and MND) was present (78.6%) N = 283, Severe HAND (HAD) (2.5%) N = 9. The factors associated with HAND were older age OR: 1.06 (95% CI: 1.03, 1.10), male gender OR: 0.48 (95% CI: 0.24, 0.97), Advanced WHO clinical staging OR: 2.45 (95% CI: 1.20, 5.01) and a higher level of education; secondary/tertiary OR: 0.16 (95% CI: 0.07, 0.38); 0.11 (95% CI: 0.04, 0.35)., Conclusion: The prevalence of HAND in this study population was found to be high (81.1%). Older age and advanced WHO clinical staging were associated with an increased risk of hand while higher level of education and male gender were protective.

Background: Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection., Methods: We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy., Results: Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation., Conclusions: Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Our aim was to compare neuropsychological and psychiatric outcomes across three encephalitis aetiological groups: Herpes simplex virus (HSV), other infections or autoimmune causes (Other), and encephalitis of unknown cause (Unknown)., Methods: Patients recruited from NHS hospitals underwent neuropsychological and psychiatric assessment in the short-term (4 months post-discharge), medium-term (9-12 months after the first assessment), and long-term (>1-year). Healthy control subjects were recruited from the general population and completed the same assessments., Results: Patients with HSV were most severely impaired on anterograde and retrograde memory tasks. In the short-term, they also showed executive, IQ, and naming deficits, which resolved in the long-term. Patients with Other or Unknown causes of encephalitis showed moderate memory impairments, but no significant impairment on executive tests. Memory impairment was associated with hippocampal/medial temporal damage on magnetic resonance imaging (MRI), and naming impairment with left temporal and left frontal abnormalities. Patients reported more subjective cognitive complaints than healthy controls, with tiredness a significant problem, and there were high rates of depression and anxiety in the HSV and the Other encephalitis groups. These subjective, self-reported complaints, depression, and anxiety persisted even after objectively measured neuropsychological performance had improved., Conclusions: Neuropsychological and psychiatric outcomes after encephalitis vary according to aetiology. Memory and naming are severely affected in HSV, and less so in other forms. Neuropsychological functioning improves over time, particularly in those with more severe short-term impairments, but subjective cognitive complaints, depression, and anxiety persist, and should be addressed in rehabilitation programmes., Competing Interests: The authors have declared that no competing interests exist.

Objective: Reduced performance in several cognitive domains has been repeatedly related to hepatitis C virus (HCV). Nevertheless, there is no consensus about the severity or cognitive profile. Moreover, other possible influential variables are scarcely controlled. The aim of this study is to define the specific cognitive profile in HCV after controlling for confounding variables., Methods: Forty-two HCV patients were distributed in 2groups according to the presence of co-infection with human immunodeficiency virus; a third group with 22 healthy controls was also included. The neuropsychological assessment included tests that assess processing speed, executive functioning, verbal memory, visual memory and working memory. Measures of depression (BDI), anxiety (HAM-A), fatigue (MAF), anhedonia (PAS), insomnia (ISI), quality of life (SF-36) and history of drug abuse (DAST-20) were taken in order to explore differences among groups and to control for their possible influence on cognitive performance., Results: HCV patients (including human immunodeficiency virus-coinfection) performed significantly worse in all cognitive measures. However, when the effect of BDI, HAM-A, MAF, ISI, SF-36 & DAST-20 was controlled, only verbal memory of HCV patients differed among groups. Coinfected patients performed worse in verbal memory., Conclusions: According to previous studies verbal memory is the unique cognitive domain related to the effect of HCV. The present study does not support that the neurovirulence effect of HCV is decreasing cognitive performance in HCV patients. Nevertheless, the present study cannot relate the fronto-striatal disruption with the cognitive performance in HCV patients., (Copyright © 2018 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.)

Approximately 59% of adults living with HIV experience HIV-associated neurocognitive disorder, a collection of symptoms and cognitive deficits in various cognitive domains. As the HIV population ages, the prevalence and severity of such cognitive deficits are expected to grow. Understanding how these cognitive deficits manifest is important for nurses and health care providers. This article provides an overview of cognitive reserve and evidence of how it is compromised by HIV, aging, and individual characteristics. Within this context of cognitive reserve, the role of neuroinflammation, neurotoxicity, substance use, comorbidities, depression and anxiety, social isolation, and sedentary lifestyle is reviewed. From this, strategies used to address cognitive deficits are provided, including topics such as psychostimulants, cognitive training, multimodal lifestyle interventions, and compensation strategies. Scenarios of successful and unsuccessful cognitive aging are presented to provide a lifespan perspective of cognitive reserve. Implications for clinical practice and research are provided, as it relates to aging.

HIV-associated neurocognitive disorders (HAND) have been linked to dysregulation of glutamate metabolism in the central nervous system (CNS) culminating in elevated extracellular glutamate and disrupted glutamatergic neurotransmission. Increased glutamate synthesis via upregulation of glutaminase (GLS) activity in brain immune cells has been identified as one potential source of excess glutamate in HAND. However, direct evidence for this hypothesis in an animal model is lacking, and the viability of GLS as a drug target has not been explored. In this brief report, we demonstrate that GLS inhibition with the glutamine analogue 6-diazo-5-oxo-L-norleucine (DON) can reverse cognitive impairment in the EcoHIV-infected mouse model of HAND. However, due to peripheral toxicity DON is not amenable to clinical use in a chronic disease such as HAND. We thus tested JHU083, a novel, brain penetrant DON prodrug predicted to exhibit improved tolerability. Systemic administration of JHU083 reversed cognitive impairment in EcoHIV-infected mice similarly to DON, and simultaneously normalized EcoHIV-induced increases in cerebrospinal fluid (CSF) glutamate and GLS activity in microglia-enriched brain CD11b + cells without observed toxicity. These studies support the mechanistic involvement of elevated microglial GLS activity in HAND pathogenesis, and identify JHU083 as a potential treatment option. Graphical Abstract Please provide Graphical Abstract caption.Glutamine Antagonist JHU083 Normalizes Aberrant Glutamate Production and Cognitive Deficits in the EcoHIV Murine Model of HIV-Associated Neurocognitive Disorders .

Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings suggested potential links between HSV-1 and Alzheimer's disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation. By virological and molecular analyses we found: i) HSV-1 spreading and replication in different brain regions after thermal stress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-β protein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1β and IL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortex and hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlated with increasing cognitive deficits becoming irreversible after seven cycles of reactivation. Collectively, our findings provide evidence that mild and recurrent HSV-1 infections in the central nervous system produce an AD-like phenotype and suggest that they are a risk factor for AD., Competing Interests: The authors have declared that no competing interests exist.

Background: The correlation among high levels of total homocysteine, low levels of B 12 vitamin, and neurocognitive impairment in HIV negative patients has been the main research topic in some of the latest reviews. The aim of this study was to examine if the alteration of homocysteine, B 12 vitamin, and D vitamins plasma levels was present in HIV-positive, and their relationship with cognitive function., Methods: 57 HIV infected were enrolled and underwent the serum measurement of homocysteine, B 12 , and D vitamins. The neurocognitive evaluation investigated 5 cognitive domains, through a neuropsychological battery test RESULTS: Homocysteine was found to be elevated in 70.2% of cases, B 12 vitamin mean levels were low in 8 participants (14.0%), and 8 patients had D hypovitaminosis (14.0%). Abnormal homocysteine levels were associated with worse performance of verbal fluency (p = 0.003) and worse executive function (Stroop E test p = 0.040). The 25-OH D hypovitaminosis was associated with worse performances in executive functions in three different tests: Stroop E (p = 0.049), Trail B (p = 0.035), and Wais Digit Span (p = 0.042). Pathological levels of B 12 Vitamin were also associated to worse performances in executive functions (Trail B Test and Wais Digit Span respectively p = 0.002 and 0.029) and with a lower speed in psychomotor processing (Peg Board Test on dominant hand, p = 0.014)., Conclusions: In this study serum homocysteine, B 12 , and D vitamin levels are associated with neurocognitive performances; in fact low performance neurocognitive was correlated with hyperhomocysteine and low B 12 vitamin, and D vitamin levels. Evidence of the alteration of these parameters could facilitate the early identification of a neurocognitive impairment.

HIV-associated neurocognitive disorders (HAND) are frequently associated with impaired executive function and verbal fluency. Given limited knowledge concerning HAND in Sub-Saharan-Africa and lack of Cameroonian adult neuropsychological (NP) test norms, we administered four executive function [Halstead Category Test (HCT), Wisconsin Card Sorting Test (WCST), Color Trails-II (CTT2), and Stroop Color-Word-Interference (SCWT)] and three verbal fluency (Category, Action, and Letter Fluency) tests to 742 adult Cameroonians (395 HIV-, 347 HIV+). We developed demographically-corrected NP test norms and examined the effects of HIV and related variables on subjects' executive function and verbal fluency. HIV+ subjects had significantly lower T-scores on CTT2 (P = 0.005), HCT (P = 0.032), WCST (P < 0.001); lower executive function composite (P = 0.002) and Action Fluency (P = 0.03) T-scores. ART, viremia, and CD4 counts did not affect T-scores. Compared to cases harboring other viral subtypes, subjects harboring HIV-1 CRF02&#95;AG had marginally higher CTT2 T-scores, significantly higher SCWT (P = 0.015) and executive function (P = 0.018) T-scores. Thus, HIV-1 infection in Cameroon is associated with impaired executive function and some aspects of verbal fluency, and viral genotype influenced executive function. We report the first normative data for assessing executive function and verbal fluency in adult Cameroonians and provide regression-based formulas for computing demographically-adjusted T-scores. These norms will be useful for investigating HIV/AIDS and other diseases affecting cognitive functioning in Cameroon.

Objective: To quantitatively measure brain glucose metabolism in treated HIV-positive individuals with [ 18 F]-labeled fluorodeoxyglucose (FDG) PET/CT., Methods: We performed a cross-sectional comparison of FDG uptake in 47 treated HIV+ individuals, 10 age-matched controls (HIV-) sharing many of the comorbid conditions seen in the HIV+ group, and 19 age-matched healthy controls (HCs). We compared whole-brain (WB) and regional FDG standardized uptake values (SUVs) of select subcortical/central structures among the groups and correlated the values to clinical and neuropsychological assessments. A variable selection model was used to predict SUVs in HIV+ (n = 47) and in combined HIV+ and HIV- participants (n = 57)., Results: We found lower WB SUVmax in HIV+ participants compared to HCs but not to HIV- participants. Among the relative SUVmean measurements (regional SUVmean/WB SUVmean), only relative thalamic uptake values were lower in HIV+ compared to HIV- participants. When HIV+ and HIV- participants were grouped, cardiovascular disease risk scores best predicted WB SUVmean and SUVmax, while HIV status best predicted thalamic relative SUVmean., Conclusions: We identified an important role for cardiovascular disease in neuronal loss/dysfunction, as measured by FDG-PET, in treated HIV+ patients. This underscores the need for shifting the focus of clinical intervention in this vulnerable population from HIV effects alone to a wider set of comorbid conditions, mainly cardiovascular disease. Only the thalamus showed significantly lower relative uptake in the HIV+ compared to the HC and HIV- groups. This needs to be further evaluated for underlying pathophysiology and potential association with memory, executive functioning, and attention deficits seen in the HIV+ population., (© 2018 American Academy of Neurology.)

Ethical and legal issues arise when a patient who is human immunodeficiency virus (HIV) positive lacks decision-making capacity and the HIV status must be disclosed to a surrogate decision maker to allow for informed medical decision making. This article discusses the special exceptions to confidentiality built into the Health Insurance Portability and Accountability Act privacy protections, the limitations on claims of common-law marriage, and public health laws that often require informing individuals who are either sex partners or needle-sharing partners of newly diagnosed HIV-infected individuals that they have been exposed to HIV infection.

Objective This study was performed to investigate the role of probiotics ( Clostridium butyricum combined with Bifidobacterium infantis) in the treatment of minimal hepatic encephalopathy (MHE) in patients with hepatitis B virus (HBV)-induced liver cirrhosis. Methods Sixty-seven consecutive patients with HBV-induced cirrhosis without overt hepatic encephalopathy were screened using the number connection test and digit symbol test. The patients were randomized to receive probiotics (n = 30) or no probiotics (n = 37) for 3 months. At the end of the trial, changes in cognition, intestinal microbiota, venous ammonia, and intestinal mucosal barriers were analyzed using recommended systems biology techniques. Results The patients' cognition was significantly improved after probiotic treatment. The predominant bacteria ( Clostridium cluster I and Bifidobacterium) were significantly enriched in the probiotics-treated group, while Enterococcus and Enterobacteriaceae were significantly decreased. Probiotic treatment was also associated with an obvious reduction in venous ammonia. Additionally, the parameters of the intestinal mucosal barrier were obviously improved after probiotic treatment, which might have contributed to the improved cognition and the decreased ammonia levels. Conclusion Treatment with probiotics containing C. butyricum and B. infantis represents a new adjuvant therapy for the management of MHE in patients with HBV-induced cirrhosis.

Combination antiretroviral therapies have revolutionized the treatment of HIV infection, and many patients now enjoy a lifespan equal to that of the general population. However, HIV-associated neurocognitive disorders (HAND) remain a major health concern, with between 30% and 70% of all HIV-infected patients developing cognitive impairments during their life time. One important feature of HAND is visuo-perceptual deficits, but the systems-level neural dynamics underlying these impairments are poorly understood. In the current study, we use magnetoencephalography and advanced time series analyses to examine these neural dynamics during a visuospatial processing task in a group of HIV-infected patients without HAND (n = 25), patients with HAND (n = 18), and a group of demographically-matched uninfected controls (n = 24). All participants completed a thorough neuropsychological assessment, and underwent magnetoencephalography and structural MRI protocols. In agreement with previous studies, patients with HAND performed significantly worse than HIV-infected patients without HAND and controls on the cognitive task, in terms of increased reaction time and decreased accuracy. Our magnetoencephalography results demonstrated that both spontaneous and neural oscillatory activity within the occipital cortices were affected by HIV infection, and that these patterns predicted behavioural performance (i.e. accuracy) on the task. Specifically, spontaneous neural activity in the alpha (8-16 Hz) and gamma (52-70 Hz) bands during the prestimulus baseline period, as well as oscillatory theta responses (4-8 Hz) during task performance were aberrant in HIV-infected patients, with both spontaneous alpha and oscillatory theta activity significantly predicting accuracy on the task and neuropsychological performance outside of the magnetoencephalography scanner. Importantly, these rhythmic patterns of population-level neural activity also distinguished patients by HAND status, such that spontaneous alpha activity in patients with HAND was elevated relative to HIV-infected patients without HAND and controls. In contrast, HIV-infected patients with and without HAND had increased spontaneous gamma compared to controls. Finally, there was a stepwise decrease in oscillatory theta activity as a function of disease severity, such that the response diminished from controls to patients without HAND to patients with HAND. Interestingly, the strength of the relationship between this theta response and accuracy also dissociated patient groups in a similar manner (controls > HIV with no HAND > HIV with HAND), indicating a reduced coupling between neurophysiology and behaviour in HIV-infected patients. This study provides the first neuroimaging evidence of a dissociation between HIV-infected patients with and without HAND, and these findings shed new light on the neural bases of cognitive impairment in HIV infection.

Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders; however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a sample consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36.07 years. A protocol of neuropsychological and psychopathological tests was applied to the participants. The group of patients with asymptomatic HIV infections significantly underperformed on tasks that assessed global cognitive screening, attention span, learning, phonemic verbal fluency, auditory-verbal comprehension, information processing speed, cognitive flexibility, and motor skills compared to the group of seronegative participants. No significant differences were found in memory, visual confrontation naming, vocabulary, inhibition, and instrumental activities of daily living. Additionally, the patients with asymptomatic HIV-1 infection had a higher anxiety index than the seronegative participants, but no significant difference was found in depression. A correlation was found between depression and anxiety. In conclusion, the patients with asymptomatic HIV-1 infection had lower cognitive performances than the seronegative participants in the cognitive functions mentioned above and more anxiety but still performed the instrumental activities of daily living.

Children and adolescents are affected in different ways by HIV/AIDS. Neurocognitive deficits are one of the most significant long term effects on HIV infected children and adolescents. Several factors are thought to influence cognitive outcomes and this include immune status, Highly Active Antiretroviral Therapy (HAART), education and social support. The aim of the study was to assess the neurocognitive function of HIV infected children and adolescents and correlate it with psychosocial factors. A cross sectional study was carried out involving a sample of 90 children living with HIV between 8 and 15 years (M = 11.38, SD = 2.06) attending Comprehensive Care Clinic (CCC) at Kenyatta National Hospital (KNH). Samples were selected by using purposive sample technique. Kaufman Assessment Battery for Children-Second Edition was used to assess cognitive function and psychosocial issues were assessed using HEADS-ED. Data was analyzed using SPSS v23 and independent T-tests, Pearson's correlation and linear regression were used. The prevalence of neurocognitive deficits among HIV positive children attending CCC at KNH was 60% with neurocognitive performance of 54 children being at least 2SD below the mean based on the KABC-II scores. There was no significant correlation between mental processing index and CD4 count (Pearson's rho =  -0.01, p = 0.39). There was no significant association between Mental Processing Index and viral load (p = 0.056) and early ARV initiation (0.27). Using the HEADS-ED, risks factors related to education (β =  -5.67, p = 0.02) and activities and peer support (β =  -9.1, p = 0.002) were significantly associated with poor neurocognitive performance. Neurocognitive deficits are prevalent among HIV positive children attending CCC-KNH. This extent of the deficits was not associated with low CD4 count, high viral load or early initiation in HIV care. However, poor school performance and problem with peers was associated with poor neurocognitive performance.

Background: Herpes simplex virus, type 1 (HSV-1) infects over 3.4 billion people, world-wide. Though it can cause encephalitis, in the vast majority it is asymptomatic, with lifelong latent infection in neurons. HSV-1 infected individuals have greater cognitive dysfunction than uninfected individuals, particularly persons with schizophrenia - even without encephalitis. We investigated whether HSV-1 related cognitive dysfunction is progressive or remediable., Methods: In a prospective naturalistic follow up sample (PNFU), temporal changes in cognitive functions were analyzed in relation to baseline HSV-1 infection in persons with/without schizophrenia (N=226). Independently, in a randomized controlled trial (RCT), HSV-1 infected, clinically stabilized SZ outpatients received Valacyclovir (VAL, an HSV-1 specific antiviral, 1.5G twice daily for 16weeks) or placebo (PLA) added to standard antipsychotic treatment, using a stratified randomization design, following placebo run-in (N=67). In both samples, HSV-1 infection (seropositivity) was estimated using serum IgG antibodies. Clinical evaluations were blinded to HSV-1 or treatment status. Standardized Z scores for accuracy on eight cognitive domains were analyzed for temporal trajectories using generalized linear models (PNFU) and VAL/PLA differences compared with intent to treat analyses (RCT)., Results: PNFU: At baseline, HSV-1 infected participants had significantly lower accuracy scores for Emotion Identification and Discrimination (EMOD), Spatial memory and Spatial ability, regardless of SZ diagnosis (p=0.025, 0.029, 0.046, respectively). They also had significantly steeper temporal worsening for EMOD (p=0.03). RCT: EMOD improved in VAL-treated patients (p=0.048, Cohen's d=0.43)., Conclusions: A proportion of age related decline in EMOD is attributable to HSV-1 infection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Importance: Despite the introduction of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders continue to be a problem for treated HIV-positive individuals. The cause of this impairment remains unclear., Objective: To determine if detectable brain changes occur during a 2-year period in HIV-positive individuals who were aviremic and treated with cART., Design, Setting, and Participants: In this longitudinal case-control study, participants underwent neuroimaging and neuropsychological assessment approximately 2 years apart. Data were collected from October 26, 2011, to March 1, 2016. Data from 92 HIV-positive individuals were acquired at Washington University in St Louis from ongoing studies conducted in the infectious disease clinic and AIDS Clinical Trial Unit. A total of 55 HIV-negative control participants were recruited from the St Louis community and a research participant registry. A total of 48 HIV-positive individuals who were aviremic and treated with cART and 31 demographically similar HIV-negative controls met the study requirements and were included in the analyses., Main Outcomes and Measures: Brain volumes were extracted with tensor-based and voxel-based morphometry and cortical modeling. Raw scores from neuropsychological tests quantified cognitive performance. Multivariable mixed-effects models assessed the effect of HIV serostatus on brain volumes and cognitive performance, and determined if HIV serostatus affected how these measures changed over time. With HIV-positive participants, linear regression models tested whether brain volumes and cognitive performance were associated with measures of infection severity and duration of infection., Results: The 2 groups were demographically similar (HIV-positive group: 23 women and 25 men; mean [SD] age, 47.7 [13.2] years; mean [SD] educational level, 13.3 [3.4] years; and HIV-negative group, 16 women and 15 men; mean [SD] age, 51.2 [12.9] years; mean [SD] educational level, 14.5 [2.1] years). The HIV-positive participants had poorer neuropsychological test scores compared with controls on the Trail Making Test Part A (5.9 seconds; 95% CI, 1.5-10.3; P = .01), Trail Making Test Part B (27.3 seconds; 95% CI, 15.0-39.6; P < .001), Digit Symbol Substitution Task (-12.5 marks; 95% CI, -18.9 to -6.0; P < .001), Letter-Number Sequencing (-2.5 marks; 95% CI, -3.7 to -1.3; P < .001), Letter Fluency (-6.6 words; 95% CI, -11.5 to -1.6; P = .01), and Hopkins Verbal Learning Test-Revised immediate recall (-2.4 words; 95% CI, -4.4 to -0.4; P = .05), after adjusting for age, sex, and educational level. Only changes in Trail Making Test Part A significantly differed between the groups. Cortical thickness and subcortical volumes were smaller in HIV-positive individuals compared with controls. However, changes in brain volume over time were similar between the groups., Conclusions and Relevance: These findings are consistent with the idea that cognitive and structural brain changes may occur early after seroconversion, and argue that maintaining aviremia with cART can prevent or minimize progressive brain injury.

Delayed brain development in perinatally HIV-infected children may affect the functional brain activity and subsequently cognitive function. The current study evaluated the functional brain activity in HIV-infected children by quantifying the amplitude of low frequency fluctuations (ALFF) and functional connectivity (FC). Additionally, correlation of ALFF and FC with cognitive measures was performed. Twenty-six HIV-infected children and 20 control children underwent neuropsychological (NP) assessment and resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and FC maps were generated and group differences were analyzed using two-sample t-test. Furthermore, ALFF and FC showing significant group differences were correlated with NP scores using Pearson's correlation. Significantly lower ALFF in the left middle temporal gyrus, precentral and post central gyrus was observed in HIV-infected children compared to controls. FC was significantly reduced in the right inferior parietal, vermis, middle temporal and left postcentral regions, and significantly increased in the right precuneus, superior parietal and left middle frontal regions in HIV-infected children as compared to control. HIV-infected children showed significantly lower NP scores in various domains including closure, exclusion, memory, verbal meaning, quantity and hidden figure than controls. These waning cognitive functions were significantly associated with changes in ALFF and FC in HIV-infected children. The findings suggest that abnormal ALFF and FC may responsible for cognitive deficits in HIV-infected children. ALFF and FC in association with cognitive evaluation may provide a clinical biomarker to evaluate functional brain activity and to plan neurocognitive intervention in HIV-infected children undergoing standard treatment., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The soluble membrane attack complex (sMAC) represents the terminal product of the complement cascade. We enrolled 47 HIV+ adults (12 of whom underwent a second visit at least 24weeks after starting therapy) as well as 11 HIV negative controls. At baseline, cerebrospinal fluid (CSF) sMAC was detectable in 27.7% of HIV+ individuals. CSF sMAC correlated with CSF HIV RNA levels and was more likely to be detectable in HIV+ individuals on cART compared to HIV negative controls. In HIV+ participants, there were negative association trends between sMAC and neurocognitive performance but these did not reach statistical significance., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine whether persistent viral suppression alters cognitive trajectories among HIV-infected (HIV+) women on combination antiretroviral therapy (cART) by investigating performance longitudinally in uninfected (HIV-) and 3 groups of HIV+ women: those with consistent viral suppression after continuous cART use (VS), those without consistent virologic suppression despite continuous cART use (NVS), and those without consistent virologic suppression after intermittent cART use (Int NVS)., Methods: Two hundred thirty-nine VS, 220 NVS, 172 Int NVS, and 301 HIV- women from the Women's Interagency HIV Study (WIHS) completed neuropsychological testing every 2 years for 3 visits between 2009 and 2013. Mixed-effects regressions were used to examine group differences on continuous T scores and categorical measures of impairment (T score <40)., Results: On global function, VS women demonstrated lower scores and were more likely to score in the impaired range than HIV- women ( p = 0.01). These differences persisted over time (group × time, p > 0.39). VS women demonstrated lower learning and memory scores than HIV- women ( p < 0.05) and lower attention/working memory and fluency scores than HIV- and NVS women ( p < 0.05). Group differences in scores persisted over time. Categorically, VS women were more likely to be impaired on attention/working memory and executive function than HIV- women ( p < 0.05). On motor skills, VS and NVS women showed a greater decline and were more likely to be impaired than HIV- women ( p < 0.05)., Conclusions: Cognitive difficulties remain among HIV+ women despite persistent viral suppression. In some instances, VS women are worse than NVS women, reinforcing the need for novel adjunctive therapies to attenuate cognitive problems., (© 2017 American Academy of Neurology.)

Objective: To present detailed information regarding these aspects in Human Immunodeficiency Virus (HIV)-infected patients making an effort to improve the recognition of neurological complications of HIV infection., Methods: This retrospective study analyzed the clinical manifestations, laboratory and neuroimaging results of HIV-infected patients with neurological complications at Xuanwu hospital, Beijing, China from January 2011 to December 2014, one of top-rated hospitals in Beijing, China., Results: A diverse range of clinical diagnoses was identified, including encephalopathy, meningoencephalitis, peripheral neuropathy, multiple sclerosis, cerebral infarction and lymphoma associated with HIV infection. The mostly observed neurological disorders were motor/sensory deficits in the limbs (75%), cognitive impairments (42%) and fever (33%). Non-specific results of laboratory tests, including elevated erythrocyte sedimentation rate (ESR), cerebrospinal fluid (CSF) protein concentration and IgG, were found. Brain Magnetic Resonance Imaging (MRI) abnormalities displayed a variety of patterns and distributions due to diverse clinical profiles., Conclusion: The clinical scenarios of HIV-infected patients are remarkably diverse and complex. Etiological tests would be cardinal to make more definitive diagnosis for HIV-infected patients. Prospective studies with follow-up were needed to bring more accurate information.

Background: The contribution of monocyte activation in the development of HIV-associated neurocognitive disorders is not completely understood. This study aimed to explore the predictive value of peripheral monocyte/macrophage (M/M) phenotypes on the evolution of cognitive performance in a population of virologically suppressed HIV-infected patients., Setting: Prospective, observational, longitudinal study., Methods: HIV-1-infected patients with HIV-RNA <50copies/mL for >12 months underwent neuropsychological examination at baseline and after 1 year. Cognitive performance was evaluated using Z-transformed scores, and neurocognitive impairment (NCI) was defined according to Frascati criteria. Peripheral M/M phenotypes (classic CD14CD16, intermediate CD14CD16, and nonclassic CD14CD16) and specific surface activation markers (eg, CD163, CD11b, and CD38) were evaluated using flow cytometry at baseline. Predictive value of peripheral M/M phenotypes on the evolution of cognitive performance over 1-year follow-up was also evaluated., Results: Overall, 54 patients [85.2% men, median age 50 years (range 27-60 years), 27.8% hepatitis C virus coinfected, 48.1% with past AIDS-defining events, median nadir CD4 83 cells/μL (range 1-334), median baseline CD4 547 cells/μL (range 136-1652)] were enrolled. Proportion of patients with NCI was low, accounting for 13% at baseline and 16.5% after 1 year (P = 0.687). Memory was the only single domain in which decreased performance after 1 year was observed (-0.25 Z-score, P = 0.025). In patients with significant decrease (≥0.5 SD) in memory performance (n = 20), significantly lower CD14CD16CD163 (% CD14CD16) (P = 0.038) and higher CD14CD38 (% CD14) (P = 0.030) levels were observed., Conclusions: In virologically suppressed HIV-infected patients, the evolution of memory performance could be linked to the expression of certain peripheral activated M/M phenotypes. Such associations should be verified in larger populations over the long term.

Human Immunodeficiency Virus (HIV) is a progressive infection that targets the immune system, affecting more than 37 million people around the world. While combinatorial antiretroviral therapy (cART) has lowered mortality rates and improved quality of life in infected individuals, the prevalence of HIV associated neurocognitive disorders is increasing and HIV associated cognitive decline remains prevalent. Recent research has suggested that HIV accessory proteins may be involved in this decline, and several studies have indicated that the HIV protein transactivator of transcription (Tat) can disrupt normal neuronal and glial function. Specifically, data indicate that Tat may directly impact dopaminergic neurotransmission, by modulating the function of the dopamine transporter and specifically damaging dopamine-rich regions of the CNS. HIV infection of the CNS has long been associated with dopaminergic dysfunction, but the mechanisms remain undefined. The specific effect(s) of Tat on dopaminergic neurotransmission may be, at least partially, a mechanism by which HIV infection directly or indirectly induces dopaminergic dysfunction. Therefore, precisely defining the specific effects of Tat on the dopaminergic system will help to elucidate the mechanisms by which HIV infection of the CNS induces neuropsychiatric, neurocognitive and neurological disorders that involve dopaminergic neurotransmission. Further, this will provide a discussion of the experiments needed to further these investigations, and may help to identify or develop new therapeutic approaches for the prevention or treatment of these disorders in HIV-infected individuals., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Glucocorticoids are released in response to stress and alter cognition and brain function through both rapid nongenomic and slow genomic mechanisms. Administration of glucocorticoids in the form of hydrocortisone enhances aspects of learning and memory in individuals with PTSD but impairs these abilities in healthy individuals. We examine the time-dependent effects of glucocorticoids on cognition in HIV-infected men., Methods: In a double-blind placebo-controlled crossover study, we examined the time-dependent effects of a single low dose of hydrocortisone [10 mg; low-dose hydrocortisone (LDH)] on cognition in 45 HIV-infected men. Participants were randomized to receive either LDH or placebo and one month later, were given the opposite treatment. At each intervention session, cognition was assessed 30 minutes (assessing nongenomic effects) and 4 hours (assessing genomic effects) after pill administration. Self-reported stress/anxiety and cortisol/cytokines in saliva were measured throughout each session., Results: Compared with placebo, LDH doubled salivary cortisol levels. Cortisol returned to baseline 4 hours postadministration. At the 30-minute assessment, LDH enhanced verbal learning compared with placebo. Greater increases in cortisol were associated with greater enhancements in verbal learning. LDH did not affect subjective stress/anxiety or any other cognitive outcomes at the 30-minute or 4-hour time point., Conclusions: The rapid effects of LDH on verbal learning suggests a nongenomic mechanism by which glucocorticoids can enhance cognition in HIV-infected men. The nonenduring nature of this enhancement may limit its clinical utility but provides insight into mechanisms underlying the effects of acute glucocorticoids on learning.

The main goal of this study was to investigate the presence of cognitive impairment in patients infected with HTLV-1 presenting or not TSP/HAM., Methods: Cross-sectional study including 104 participants: 37 asymptomatic HTLV-1 carriers, 37 patients diagnosed with TSP/HAM and 30 HTLV-1 negative control patients. Within the HTLV-1 positive group, 53 were female and 21 were male, the average age was 46 (SD=13.5) and the average schooling time was 7.7years (SD=3.3).The sociodemographic variables (genre, age and education) were compared between the three groups. The assessment tools used were: Beck Depression Inventory, Lawton's Activities of Daily Life Scale and a complete neuropsychological battery. The application of these assessment tools was carried out in blind. Both HTLV-1 asymptomatic subjects and HAM/TSP patients showed a lower performance on neuropsychological tests and higher depression scores when compared to the control group. HTLV-1 patients performed poorly in several cognitive domains, but only fluid intelligence, estimated intellectual functioning, immediate and delayed recall of visual memory and information processing speed (in the specific case of patients with TSP/HAM) reached statistical significance when compared with controls. Depression was not associated with cognitive impairment. HTLV-1 carriers presented a higher frequency of cognitive impairment than normal controls., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Because of neurocognitive impairments in perinatally human immunodeficiency virus (HIV)-infected children and adolescents, this study aimed to demonstrate the effect of plasma viral loads and early initiation of sufficient combined antiretroviral therapy (cART) on neurocognitive development.In total, 14 perinatally infected HIV-positive children (median age 8.24 years [range: 6.0-16.74]) receiving lopinavir/ritonavir (LPV/r)-based ART underwent neurocognitive testing using the Wechsler Intelligence Score for Children, 4th Edition (WISC-IV). All 14 patients participated in a pharmacokinetic study in which they were hospitalized for an entire day. As a child's ability to concentrate varies over the course of the day, all tests were performed in the morning.The patients' neurocognitive development did not significantly differ from the normative collective pattern for any of the following composite scores that were examined: full-scale intelligence quotient (IQ) (mean: 106.5, P = .1060), verbal comprehension index (mean: 106.0, P = .1356), perceptual reasoning index (mean: 106.0, P = .1357), working memory index (mean: 106.3, P = .1171), and processing speed index (mean: 98.1, P = .6313). The overall full-scale IQ scores were significantly higher in children who began ART within the first year of life (P = .0379), whereas low lopinavir/r plasma levels (P = .0070) and high viral load area under the curves (AUCs) in the first 3 years of life, but not later, significantly correlated with reduced neurocognitive performance (Spearman r = -0.64, P = .0278).In this cohort of cART treated HIV-positive children and adolescents, neurocognitive performance correlated with early and sufficient viral load suppression within the first 3 years of life.

A 57-year-old male steel plant worker presented with fatigue and altered liver function tests. Over the next two years, he developed cognitive decline, parkinsonism and seizures. This paper reports the clinicopathological conference at the 37th Edinburgh Advanced Neurology Course 2015 and outlines what we can learn from this case., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background:  Cognitive impairment persists despite suppression of plasma human immunodeficiency virus (HIV) RNA. Monocyte-related immune activation is a likely mechanism. We examined immune activation and cognition in a cohort of HIV-infected and uninfected women from the Women's Interagency HIV Study (WIHS)., Methods:  Blood levels of activation markers, soluble CD163 (sCD163), soluble CD14 (sCD14), CRP, IL-6, and a gut microbial translocation marker (intestinal fatty acid binding protein (I-FABP)) were measured in 253 women (73% HIV-infected). Markers were compared to concurrent (within ± one semiannual visit) neuropsychological testing performance., Results:  Higher sCD163 levels were associated with worse overall performance and worse verbal learning, verbal memory, executive function, psychomotor speed, and fine motor skills (P < .05 for all comparisons). Higher sCD14 levels were associated with worse verbal learning, verbal memory, executive function, and psychomotor speed (P < .05 for all comparisons). Among women with virological suppression, sCD163 remained associated with overall performance, verbal memory, psychomotor speed, and fine motor skills, and sCD164 remained associated with executive function (P < .05 for all comparisons). CRP, IL-6, and I-FABP were not associated with worse cognitive performance., Conclusions:  Monocyte activation was associated with worse cognitive performance, and associations persisted despite viral suppression. Persistent inflammatory mechanisms related to monocytes correlate to clinically pertinent brain outcomes., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Introduction: HIV is frequently associated with deficits in brain function, including memory, psychomotor speed, executive function and attention. Early life stress (ELS) has also been shown to have a direct influence on neurocognitive performance. However, little is known about the combined impact of ELS and HIV on neurocognitive function over time. The aim of the present study was to follow a cohort of affected women, allowing us to assess the effects of HIV and childhood trauma on cognition and the change in cognition over time., Method: A battery of neurocognitive tests was administered to 117 women at baseline and then a year later. The sample included a total of 67 HIV + and 50 HIV - women, 71 with ELS and 46 without ELS. Controlling for age, education and antiretroviral therapy (ART) at baseline and 12-month follow-up, raw scores were compared across groups using a repeated-measures analysis of covariance., Results: More women were on ART at follow-up compared to baseline. Results revealed a significant combined HIV and childhood trauma effect over time on the Wisconsin Card Sorting Test (p = .003) and Category Fluency Test (p = .006). A significant individual HIV effect over time was evident on the WAIS-III Digit Symbol Test (p = .03) and the Controlled Oral Word Association Test (p = .003)., Conclusion: Findings suggest better performance in abstract reasoning, speed of information processing and verbal fluency over time. While all groups showed improvements that may correspond to practice effects, effects of HIV and childhood trauma remained evident at 12-month follow-up despite greater ART uptake and improved HIV disease status. This is the first study to assess the combined impact of HIV and trauma on neurocognitive function over time in an all-female cohort with more advanced disease., Competing Interests: We have no conflict of interest to declare.

Background: Combination antiretroviral therapy has led to increased survival among youth with perinatally acquired HIV (PHIV). However, cognitive deficits continue to be common. Histopathological studies in adults have found HIV concentrated in subcortical structures, which are involved in sensory processing, movement, and higher-order cognition that emerges with development., Methods: We conducted magnetic resonance imaging and cognitive testing in 40 youth with PHIV at one site of the Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study. We collected HIV disease-severity measures and substance-use reports. Subcortical volume and shape deformation were generated with FreeSurfer-Initiated Large Deformation Diffeomorphic Metric Mapping. Inward shape deformation was defined as negative displacement. We evaluated associations of subcortical shape deformation with past HIV severity after adjustment for sex, age at neuroimaging, age at HIV severity marker, and substance use. We examined associations between subcortical deformation and cognitive function., Results: Negative correlations between shape deformation and peak HIV viral load (VL) were found in clusters in the caudate tail, globus pallidus, lateral putamen, and anterior and medial thalamus. Positive correlations between shape deformation and nadir CD4-positive T-lymphocyte percentage (CD4%) were found in clusters in the medial and posterior thalamus. Inward deformation in caudate and thalamic clusters correlated with worse cognition., Conclusions: Youth with PHIV have demonstrable subcortical shape deformation related to past HIV severity and cognition; inward deformation was associated with higher peak VL, lower nadir CD4%, and worse cognition. Identifying subcortical deformation may inform clinical practice for early intervention to help improve cognitive outcomes and assess the neuroefficacy of combination antiretroviral therapy in youth with PHIV., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Antiretroviral therapy has revolutionised the treatment for people living with HIV (PLWH). Where antiretroviral coverage is high, the treatment paradigm for HIV-disease is now one of managing the long-term consequences of the virus and its treatment rather than the consequences of untreated HIV-disease such as immunosuppression and opportunistic infections. One such long-term consequence is HIV-associated cognitive impairment which is reported to occur in up to 50 % of treated PLWH and has been associated with poorer outcomes. Given the ageing cohort and increased frequency of comorbidities, the prevalence of symptomatic cognitive impairment may increase with time. High quality evidence for management strategies including screening, diagnosis and treatment of HIV-associated cognitive impairment are lacking and in general guidelines are based on best clinical practice. In this article, we assessed recent guidelines concerning the management of HIV-associated cognitive impairment by performing a systematic review of the MEDLINE database using PubMed. We report that, in general, guidelines from around the world regarding the management of HIV-associated cognitive impairment are converging. Screening is generally not recommended in asymptomatic PLWH. Diagnosis of HIV-associated cognitive impairment should be made only after a comprehensive assessment and exclusion of other potential causes. Antiretroviral therapy forms the cornerstone of management of HIV-associated cognitive impairment and should be guided by plasma and cerebrospinal fluid (CSF) genotype(s)., Competing Interests: Jonathan Underwood has received a travel grant from Gilead Sciences to facilitate his attendance at the EACS conference 2015 and British HIV Association grant (from MSD) to attend CROI. Alan Winston has received honoraria or research grants, or has been a consultant or investigator, in clinical trials sponsored by Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen Cilag, Roche, Pfizer and ViiV Healthcare. Funding J.U. and A.W. are grateful to the NIHR Biomedical Facility at Imperial College London for infrastructure support. This work was supported by funding from the European Union as part of an FP7 grant: COBRA (Co-morbidity in relation to AIDS grant number 305522).

Previous investigations have found that smokers with schizophrenia demonstrate reduced performance on cognitive tasks compared to non-smokers. However previous studies have not taken into account other environmental factors associated with cognitive functioning such as exposure to Herpes Simplex Virus type 1 (HSV-1). We examined these factors in a sample consisting of individuals with schizophrenia (n=773), bipolar disorder (n=493), or controls without a psychiatric disorders (n=548). Participants were assessed on a cognitive battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and had a blood sample drawn to measure seropositivity to HSV-1. Within each group linear regression models were constructed to determine whether cigarette smoking and HSV-1 seropositivity were jointly associated with cognitive functioning after adjusting for relevant covariates. Within the schizophrenia group, the effect size of lower total cognitive score was -0.279 (p<0.0001) for individuals who were both smokers and HSV-1 seropositive and a significant effect was found in all cognitive domains. The odds of being in the highest quartile of RBANS Total score were significantly lower for smokers (OR=0.58, 95% CI 0.41, 0.82, p=0.002). Smoking was not as consistently associated with levels of cognitive functioning in the bipolar disorder or the non-psychiatric control group. While experimental studies show that nicotine transiently improves functioning on sensory gating and attention tasks known to be deficient in schizophrenia, long-term nicotine exposure via smoking appears to have an adverse effect on cognitive functioning., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of our study was to evaluate the impact of coffee intake on cognitive function in persons living with HIV (PLWH). 130 PLWH with CD4 > 200 cells/mm(3), undetectable viral load, treated with HAART were included. A structured interview was applied and relevant clinical and laboratory data were assessed, including coffee intake. For neuropsychological assessment, the HIV Neurobehavioral Research Center Battery was chosen. Univariate nonparametric statistics and multivariate regression model were used. A significant association between espresso coffee use and a better cognitive function was verified in five of the eight psychometric measurements. In the multivariate analysis, after variable adjustment, linear regression analysis showed that coffee intake was a positive predictor for attention/working memory, executive functions and Global Deficit Score. Although the mechanisms behind the influence of caffeine on cognitive functioning are controversial, regular espresso coffee intake may have favourable effects on cognitive deterioration caused by HIV.

Neuroinflammation induced during immune responses to viral infections in the brain affect behavior. Unexpected evidence that oral gavage of an algal virus in its host algal cells could alter cognition was further examined by directly injecting purified algal virus ATCV-1 intracranially into C57BL/6 mice. After 4weeks, the ATCV-1 infection impaired delayed location recognition memory, and also reduced and anxiety. Corresponding to these effects, heightened ATCV-1, IL-6, iNOS, IFN-γ, and CD11b expression in brains was observed 3-days and/or 8-weeks post infection compared with control mice. These results imply that ATCV-1 infection damages the hippocampus via induction of inflammatory factors., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The emotional processing in human immunodeficiency virus-seropositive individuals (HIV+) has been scarcely studied. We included HIV+ individuals (n = 107) on antiretroviral therapy (≥2 years) who completed 6 facial processing tasks and neurocognitive testing. We compared HIV+ and healthy adult (HA) participants (n = 40) in overall performance of each facial processing task. Multiple logistic regressions were conducted to explore predictors of poorer accuracy in those measures in which HIV+ individuals performed poorer than HA participants. We separately explored the impact of neurocognitive status, antiretroviral regimen, and hepatitis C virus (HCV) coinfection on the tasks performance. We found similar performance in overall facial emotion discrimination, recognition, and recall between HIV+ and HA participants. The HIV+ group had poorer recognition of particular negative emotions. Lower WAIS-III Vocabulary scores and active HCV predicted poorer accuracy in recognition of particular emotions. Our results suggest that permanent damage of emotion-related brain systems might persist despite long-term effective antiretroviral therapy., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-β (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline., (© The Author 2015. 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.)