Cognitive impairment among older adults with HIV: a systematic review protocol of cohort studies / Transtornos cognitivos em idosos vivendo com HIV: protocolo de revisão sistemática com estudos de coorte

OBJECTIVES: This review will determine whether the incidence of cognitive impairment in HIV patients aged ≥ 50 years is greater than that of their HIV-negative peers. METHODS: The MEDLINE, EMBASE, LILACS, Web of Science, and Scopus databases will be searched for studies with a sample of individuals aged ≥ 50 years or a mixed population with ≥ 50% aged ≥ 50 years). It will include studies that evaluate seropositive patients compared to and an unexposed control group. STUDY DESIGN: Cohort studies with follow-up ≥ 24 months will be included. Three reviewers will independently screen for eligibility criteria, extract data, and assess the risk of bias in the included studies, as well as evaluate the overall quality of evidence. A narrative synthesis will be prepared according to synthesis without meta-analysis guidelines. EXPECTED RESULTS: We expect to find correlations between older age, HIV, and cognitive impairment. RELEVANCE: The association of geriatric syndromes and HIV is becoming an important field of study. Increased life expectancy accompanied by an active sex life is contributing to this public health problem. This protocol is reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and is registered in PROSPERO (CRD42022321914). This study was financed in part by the CAPES foundation (financial code: 001)

OBJETIVOS: Esta revisão abordará o questionamento: a incidência de comprometimento cognitivo é maior em pacientes com 50 anos ou mais com o vírus da imunodeficiência humana do que em idosos soronegativos? METODOLOGIA: As bases de dados Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Web of Science e Scopus serão pesquisadas. A estratégia de busca considerará estudos com amostra de 50 anos ou mais e população mista (pelo menos 50% com 50 anos ou mais). Incluirá estudos que avaliam pacientes soropositivos, e o controle considerará pesquisas que abordem pessoas não expostas. DESENHO DO ESTUDO: Serão incluídos estudos de coorte com seguimento de pelo menos 24 meses. Três revisores, de forma independente, farão a triagem dos artigos quanto aos critérios de elegibilidade, extrairão dados, avaliarão o risco de viés dos trabalhos e avaliarão a qualidade geral das evidências. Uma síntese narrativa será preparada de acordo com a diretriz SWiM. RESULTADOS ESPERADOS: Esperamos encontrar maior incidência de comprometimento cognitivo em idosos que vivem com o vírus da imunodeficiência humana. RELEVÂNCIA: As síndromes geriátricas associadas ao HIV tornam-se um importante escopo de estudo, uma vez que, o aumento da expectativa de vida acompanhado de uma vida sexual ativa sustenta o ciclo de contaminação desse problema de saúde pública. Este protocolo é relatado de acordo com os Itens Preferenciais de Relatórios para Protocolos de Revisão Sistemática e Metanálise e está registrado no International Prospective Register of Systematic Reviews ­ PROSPERO (CRD42022321914). Este estudo foi parcialmente financiado pela Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ­ Brasil ­ Código de financiamento: 001

Post-acute COVID-19 Syndrome Negatively Impacts Physical Function, Cognitive Function, Health-Related Quality of Life, and Participation.

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.

Activation of Endogenous Retrovirus, Brain Infections and Environmental Insults in Neurodegeneration and Alzheimer's Disease.

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.

Improved neurocognitive performance in FIV infected cats following treatment with the p75 neurotrophin receptor ligand LM11A-31.

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 (p75NTR) 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.

COVID-19 cognitive deficits after respiratory assistance in the subacute phase: A COVID-rehabilitation unit experience.

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.

White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling.

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.

Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets.

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.

Atypical symptoms of COVID-19 in hospitalised oldest old adults / Síntomas atípicos de COVID-19 en el adulto mayor hospitalizado

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Cognitive impact of COVID-19: looking beyond the short term.

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-ß (Aß) 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.

Neurocognitive impacts of arbovirus infections.

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.

HIV-associated neurocognitive disorders at Moi teaching and referral hospital, Eldoret, Kenya.

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.

Effects of COVID-19 on Parkinson's Disease Clinical Features: A Community-Based Case-Control Study.

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.

Neuropsychological and psychiatric outcomes in encephalitis: A multi-centre case-control study.

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.

Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms.

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.

Efecto de los síntomas psiquiátricos y calidad de vida sobre el desempeño cognitivo en el VHC / Effect of psychiatric symptoms and quality of life on cognitive performance in HCV patients

OBJETIVO: El virus de la hepatitis C (VHC) se ha relacionado repetidamente con un peor rendimiento de las funciones cognitivas. Sin embargo, no existe consenso acerca de la gravedad o del tipo de afectación cognitiva. Además, rara vez se controlan las variables que puedan influir en ello. El objetivo del presente estudio es definir el perfil cognitivo de los pacientes con VHC tras controlar el efecto de posibles covariables. MÉTODOS: Se dividió a 42 pacientes con VHC en 2 grupos según la existencia de coinfección con virus de la inmunodeficiencia humana y se incluyó a un tercer grupo de 22 controles sanos. La evaluación neuropsicológica incluyó medidas de velocidad de procesamiento, funciones ejecutivas, memoria verbal, memoria visual y memoria de trabajo. Para explorar diferencias e identificar posibles covariables se tomaron medidas de depresión (BDI), ansiedad (HAM-A), fatiga (MAF), anhedonia (PAS), insomnio (ISI), calidad de vida (SF-36) y antecedentes de consumo de drogas (DAST-20). RESULTADOS: Los pacientes con VHC (incluyendo coinfectados por virus de la inmunodeficiencia humana) tuvieron un rendimiento peor que el grupo control en todos los dominios cognitivos. Sin embargo, tras controlar el efecto de BDI, HAM-A, MAF, ISI, SF-36 y DAST-20, solo la memoria verbal de los pacientes con VHC mostró diferencias entre los grupos. CONCLUSIONES: En consonancia con estudios previos, nuestros resultados muestran una relación entre la memoria verbal y el efecto del VHC en el cerebro, aunque el presente estudio no ha podido relacionar la afectación frontoestriatal de los pacientes con VHC con su rendimiento cognitivo

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

Effect of psychiatric symptoms and quality of life on cognitive performance in HCV patients. / Efecto de los síntomas psiquiátricos y calidad de vida sobre el desempeño cognitivo en el VHC.

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.

Glutamine Antagonist JHU083 Normalizes Aberrant Glutamate Production and Cognitive Deficits in the EcoHIV Murine Model of HIV-Associated Neurocognitive Disorders.

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 .

Cognitive Reserve Over the Lifespan: Neurocognitive Implications for Aging With HIV.

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.