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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 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.)

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults., (Copyright © 2015 Elsevier Inc. All rights reserved.)

HIV-associated neurocognitive disorders (HAND) are one of major comorbidities in patients with HIV-1 infection. There are currently no standardized tests for screening HAND in such patients. The sensitivity of the cognitive function tests routinely used in clinical practice, such as the Mini-Mental State Examination and the Revised Hasegawa's Dementia Scale, is inadequate to rule out HAND, even in patients with clear abnormal behavior. We report a 41-year-old man with HIV-associated dementia, the most severe form of HAND, in whom the simplified methods did not show abnormal results, and a comprehensive battery of neuropsychological tests which covering several cognitive domains was needed to detect cognitive impairment., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: Youth living with human immunodeficiency virus (HIV) account for over one third of new HIV infections and are at high risk of adverse psychosocial, everyday living, and health outcomes. Human immunodeficiency virus-associated neurocognitive disorders (HAND) are known to affect health outcomes of HIV-infected adults even in the era of combination antiretroviral therapy. Thus, the current study aimed to characterize the prevalence and clinical correlates of HAND in youth living with HIV. Here, we report baseline neurocognitive data for behaviorally HIV-infected youth enrolled in a prospective study evaluating strategies of antiretroviral treatment initiation and use., Methods: A total of 220 participants, age 18-24 years, who were naive to treatment (except for prevention of mother-to-child HIV transmission; n = 3), completed a comprehensive neurocognitive, substance use, and behavioral health assessment battery., Results: Sixty-seven percent of youth met criteria for HAND (96.4% were asymptomatic and 3.5% were syndromic); deficits in episodic memory and fine-motor skills emerged as the most commonly affected ability areas. Multivariable models showed that lower CD4 count, longer time since HIV diagnosis, and high-risk alcohol use were uniquely associated with neurocognitive deficits., Conclusions: Over two thirds of youth with behaviorally acquired HIV evidence neurocognitive deficits, which have modest associations with more advanced HIV disease as well as other factors. Research is needed to determine the impact of such neuropsychiatric morbidity on mental health and HIV disease treatment outcomes (e.g., nonadherence) and transition to independent living responsibilities in HIV-infected youth, as well as its long-term trajectory and possible responsiveness to cognitive rehabilitation and pharmacotherapy., (Copyright © 2013 Society for Adolescent Health and Medicine. All rights reserved.)

Objectives: We aimed to characterize neurological outcomes and determine the prevalence of HIV encephalopathy in a cohort of HIV-infected children in Jamaica., Methods: Data for 287 HIV-infected children presenting between 2002 and 2008 were reviewed and neurological outcomes characterized. A nested case-control study was conducted between July and September 2009 used 15 randomly selected encephalopathic HIV-infected children aged 7-10 years and 15 matched controls (non-encephalopathic HIV-infected). Their neurocognitive functions were evaluated using clinical assessment and standardized tests for intelligence, short term memory (visuo-spatial and auditory), selective attention, and fine motor and coordination functions. Outcomes were compared using Fisher's exact test and the Mann-Whitney U-test., Results: Sixty-seven (23.3%) children were encephalopathic. The median age at diagnosis of HIV encephalopathy was 1.6 years (interquartile range (IQR) 1.1-3.4 years). Predominant abnormalities were delayed milestones (59, 88.1%), hyperreflexia (59, 86.5%), spasticity (50, 74.6%), microcephaly (42, 61.7%), and quadriparesis (21, 31.3%). The median age of tested children was 8.7 years (IQR 7.6-10.8 years) in the encephalopathic group and 9 years (IQR 7.4-10.7 years) in the non-encephalopathic group. Encephalopathic children performed worse in all domains of neurocognitive function (p<0.05)., Conclusions: A high prevalence of HIV encephalopathy was noted, and significant neurocognitive dysfunction identified in encephalopathic children. Optimized management through the early identification of neurological impairment and implementation of appropriate interventions is recommended to improve quality of life., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Cytomegalovirus infection has been implicated in cognitive impairment in studies using brief clinical assessments though findings are inconsistent. The association between cytomegalovirus infection, measured as serostatus or a semiquantitative assessment of antibody level, and cognitive abilities in a sample of older adults was examined. Cytomegalovirus status was assessed at a mean age of 70 years in 1061 participants of the Lothian Birth Cohort 1936. Cognitive ability scores were available for general cognitive ability, processing speed, memory, and vocabulary. Background demographic and environmental factors included father's social class, years of education, childhood cognitive ability, overcrowding in childhood, and access to indoor toilet facilities. Cytomegalovirus seropositive individuals had lower cognitive ability at age 70: mean IQ was 99.1 (SD, 15.1) versus 102.4 (SD, 13.1) in seronegative individuals (t = 3.65; p < 0.001). The likelihood of contracting cytomegalovirus infection by age 70 was predicted by a number of demographic and environmental factors and, after accounting for these, cytomegalovirus infection (considered as serostatus) was not cognitively detrimental. Within cytomegalovirus seropositive individuals, however, higher cytomegalovirus antibody levels were associated with lower general cognitive ability., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background & Aims: Chronic hepatitis C virus (HCV) infection is associated with altered cerebral metabolism and cognitive dysfunction. We aimed to evaluate the effect of pegylated interferon/ribavirin (PIFN/R) and HCV clearance on cerebral metabolism, and neuropsychological performance., Methods: Fifteen non-cirrhotic HCV positive subjects underwent (1)H MR spectroscopy (MRS) before, during, and after treatment with PIFN/R. The metabolites of interest namely, N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), and the control metabolite creatine (Cr), were acquired from 3 different brain regions; left basal ganglia, left frontal cortex, and left dorso-lateral pre-frontal cortex. Coinciding with this, subjects also underwent a battery of neuropsychological tests to evaluate the domains of verbal learning, memory, attention, language, executive functioning, and motor skills. Seven HCV positive controls (not receiving anti-viral therapy) underwent MRS and neuropsychological testing at two time points, 12 weeks apart, to examine for variation in cerebral metabolites over time and the practice effect of repeat neuropsychological testing., Results: Significant reductions in basal ganglia Cho/Cr (p=0.03) and basal ganglia MI/Cr (p=0.03) were observed in sustained virological responders (SVRs, n=8), but not non-responders/relapsers (NR/R, n=6), indicative of reduced cerebral infection and/or immune activation in those who cleared virus. SVRs demonstrated significant improvements in verbal learning, memory, and visuo-spatial memory. A small but significant improvement in neurocognitive function secondary to the practice effect was seen in both HCV controls and HCV subjects during treatment., Conclusions: HCV eradication has a beneficial effect on cerebral metabolism and selective aspects of neurocognitive function and is an important factor when contemplating anti-viral therapy in HCV, especially in those with mild disease., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Previous studies have reported that hepatitis C virus (HCV) co-infection worsens neurocognitive status among individuals with human immunodeficiency virus (HIV)-1 infection. We assessed the prevalence of neurologic disorders and the severity of HIV-associated neurocognitive impairment among HIV-infected individuals in two centralized HIV clinics in Alberta, Canada from 1998 to 2010 based on their HCV serostatus. Of 456 HIV-infected persons without concurrent substance abuse, 91 (20.0%) were HCV seropositive. Of 58 neurologic disorders identified in the cohort, HIV/HCV co-infected individuals exhibited a higher prevalence of multiple neurologic disorders compared to HIV-infected individuals (60.4% vs. 46.6%, p<0.05) and a higher frequency of seizures (28.6% vs. 17.8%, p<0.05). Unlike HIV mono-infected persons, the risk of seizures was independent of immune status in HIV/HCV co-infected individuals (p<0.05). Symptomatic HIV-associated neurocognitive disorders (sHAND) were more severe among HIV/HCV co-infected persons (p<0.05). HCV co-infection was associated with an increased mortality rate (24.2% vs. 14.5%, p<0.05) with a mortality hazard ratio of 2.38 after adjusting for demographic and clinical variables. Our results indicate that the presence of HCV co-infection among HIV-infected individuals increased neurologic disease burden and risk of death, underscoring HCV's capacity to affect the nervous system and survival of HIV-infected persons., (Copyright © 2011. Published by Elsevier B.V.)

Human herpesvirus 6 (HHV-6) is detected in the plasma of approximately 40% of patients undergoing hematopoietic cell transplantation (HCT) and sporadically causes encephalitis in this population. The effect of HHV-6 reactivation on central nervous system function has not been fully characterized. This prospective study aimed to evaluate associations between HHV-6 reactivation and central nervous system dysfunction after allogeneic HCT. Patients were enrolled before HCT. Plasma samples were tested for HHV-6 at baseline and twice weekly after transplantation until day 84. Delirium was assessed at baseline, 3 times weekly until day 56, and weekly on days 56 to 84 using a validated instrument. Neurocognitive testing was performed at baseline and at approximately day 84. HHV-6 was detected in 111 (35%) of the 315 included patients. Patients with HHV-6 were more likely to develop delirium (adjusted odds ratio = 2.5; 95% confidence interval, 1.2-5.3) and demonstrate neurocognitive decline (adjusted odds ratio = 2.6; 95% confidence interval, 1.1-6.2) in the first 84 days after HCT. Cord blood and unrelated transplantation increased risk of HHV-6 reactivation. These data provide the basis to conduct a randomized clinical trial to determine whether prevention of HHV-6 reactivation will reduce neurocognitive morbidity in HCT recipients.

Background and Purpose: Human immunodeficiency virus (HIV)-associated dementia (HAD) has been extensively studied using magnetic resonance spectroscopy (MRS) at field strengths of 1.5 T. Higher magnetic field strengths (such as 3 T) allow for more reliable determination of certain compounds, such as glutamate (Glu) and glutamine (Gln). The current study was undertaken to investigate the utility of 3-T MRS for evaluating HIV+ patients with different levels of cognitive impairment with emphasis on the measurement of Glu and Glx (the sum of Glu and Gln)., Methods: Eighty-six HIV+ subjects were evaluated at 3 T using quantitative short echo time single-voxel MRS of frontal white matter (FWM) and basal ganglia (BG). Subjects were divided into three groups according to the Memorial Sloan Kettering (MSK) HIV dementia stage: 21 had normal cognition (NC) (MSK 0), 31 had mild cognitive impairment (MCI) without dementia (clinical MSK stage=0.5), and 34 had dementia (HAD) (MSK≥1). HIV+ subjects had also undergone standardized cognitive testing covering the domains of executive function, verbal memory, attention, information processing speed and motor and psychomotor speed. Between-group differences in metabolite levels in FWM and BG were evaluated using ANOVA. Pearson correlation coefficients were used to explore the associations between the Glu and Glx metabolites and neurocognitive results., Results: FWM Glx was lower in HAD (8.1 ± 2.1 mM) compared to both the MCI (9.17 ± 2.1 mM) and NC groups (10.0 ± 1.6 mM) (P=.006). FWM myo-inositol (mI) was higher in HAD (4.15 ± 0.75 mM) compared to both MCI (3.86 ± 0.85 mM) and NC status (3.4 ± 0.67 mM) (P=.006). FWM Glx/creatine (Cr) was lower and FWM mI/Cr was significantly higher in the HAD compared to the MCI and NC groups (P=.01 and P=.004, respectively). BG N-acetyl aspartate (NAA) was lower in the HAD group (6.79 ± 1.53 mM), compared to the MCI (7.5 ± 1.06 mM) and NC (7.6 ± 1.01 mM) groups (P=.036). Significant negative correlations were observed between Glu, Glx and NAA concentrations with Trail-Making Test B (P=.006, P=.0001 and P=.007, respectively), and significant positive correlation was found with the Digit symbol test (P=.02, P=.002 and P=.008, respectively). FWM Glx and NAA concentrations showed negative correlation with Grooved Pegboard nondominant hand (P=.02 and P=.04, respectively)., Conclusion: Patients with HAD have lower levels of Glx concentrations and Glx/Cr ratio in FWM, which was associated with impaired performance in specific cognitive domains, including executive functioning, fine motor, attention and working memory performance. Three-Tesla MRS measurements of Glx may be a useful indicator of neuronal loss/dysfunction in patients with HIV infection., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Previous studies have documented that serologic evidence of infection with the neurotropic human herpesvirus Herpes Simplex Virus type 1 (HSV-1) is associated with increased levels of cognitive dysfunction in individuals with schizophrenia or bipolar disorder. The catechol-o-methyl transferase (COMT) Val158Met polymorphism has also been associated with cognitive dysfunction in individuals with psychiatric disorders as well as in some control populations. We examined whether these factors are independently associated with cognitive functioning in adults without a history of a psychiatric disorder. A total of 240 individuals were evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Wisconsin Card Sorting Test (WCST). We measured IgG antibodies to HSV-1 by enzyme immunoassay and employed real time PCR to measure COMT Val158Met genotypes. Serological evidence of HSV-1 was significantly associated with a lower RBANS total score independent of demographic factors and the COMT Val158Met genotype. The strongest association between cognitive functioning and serological evidence of HSV-1 infection was with the domain of delayed memory. Serological evidence of HSV-1 infection was associated with an 18-fold increased odds of having a severe impairment in this domain. The Val/Val genotype of the COMT Val158Met polymorphism was also significantly associated with the RBANS total score and with a moderate decrease in the domain of attention. Infections with HSV-1 and the COMT Val158Val genotype are risk factors for cognitive deficits in non-elderly persons without a psychiatric disorder.

Studies of cognitive function in individuals with HIV infection who remain relatively asymptomatic have shown widely variable estimates of impairment in different races and countries. Limited data exist on the impact of early asymptomatic HIV infection on cognition in developing nations, and indeed none from Nigeria. Hence, this cross-sectional study sets out to determine whether there are differences between Nigerian asymptomatic HIV-seropositive and HIV-seronegative subjects, and whether such differences: if any, could be explained by the degree of immunosuppression (i.e. CD4 cell count). A selected population of 60 heterosexual asymptomatic treatment-naive HIV-positive subjects were administered the Community Screening Instrument for Dementia (CSI-D) to assess language, memory, registration, attention and calculation, recall, praxis and orientation. HIV positives differed from individually matched control subjects in certain measures of language expression, registration, attention and calculation, orientation to time, motor response and total CSI-D scores. The CD4 cell count of the HIV-seropositive subjects had no significant correlation with the cognitive test scores.

While high age, low level of education and APOE epsilon4 allele are known to predict dementia, there is recent data suggesting that certain viruses and subtypes of APOE epsilon3 could be involved, too. We investigated these relationships in a home-dwelling cohort of 357 elderly people with various cardiovascular diseases (DEBATE study). MMSE score below 24 was used to define cognitive impairment (n = 58). When adjusted for age and the presence of diabetes, multivariate analysis demonstrated maximally increased risk of cognitive impairment in association with a combination of three factors: seropositivity for herpesviridae, presence of APOE epsilon4, and low education (risk ratio 6.1, 95% CI 2.4-15.2). In the subcohort of APOE3/3 individuals (n = 216) homozygosity for the -219G epsilon3 haplotype showed a similar association (risk ratio 8.8, 95% CI 2.6-29.8). These results demonstrate an interaction of specific genetic (APOE) and environmental (education and herpesviridae) risk factors in the development of cognitive impairment and indicate that not only the epsilon4 allele of APOE but also the epsilon3 haplotype is a risk factor for dementia.

Background/aims: Up to 50% of patients infected with the hepatitis C virus (HCV) complain of chronic fatigue and difficulties in concentration and memory. The aim of the present study was to seek evidence for the presence of central nervous system involvement in HCV infected patients with only mild liver disease., Methods: Thirty HCV infected patients with normal liver function, 15 of whom were identified as having mild and 15 moderate to severe fatigue using the fatigue impact scale, underwent neurological and neuropsychological examination, electroencephalography (EEG) and cerebral proton magnetic resonance imaging (MRI) and spectroscopy (MRS). Fifteen healthy volunteers, matched for age and educational attainment, served as controls., Results: In comparison to the healthy controls the patients with HCV infection showed evidence of cognitive impairment, primarily attention and higher executive functions, higher levels of anxiety and depression and impairment of quality of life. In addition they showed a significant decrease of the N-acetyl-aspartate/creatine ratio in the cerebral cortex on 1H MRS while the EEG was slowed in 25%. In general the deficits were more marked in the patients with moderate rather than mild fatigue., Conclusions: The data provide evidence of central nervous system involvement in patients with HCV infection.

Background: In a previous investigation, we found an association between reduced cognitive functioning and the prevalence of antibodies to herpes simplex virus type 1 in individuals with schizophrenia. The current study was undertaken to determine if this association also occurs in individuals with bipolar disorder., Methods: Cognitive functioning and serologic evidence of infection with potentially neurotropic herpesviruses were measured in 117 individuals with bipolar disorder and in 100 individuals without a history of psychiatric disorder. Cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status. For each patient, serologic evidence of infection was ascertained by the measurement of serum immunoglobulin G class antibodies with specificities for six potentially neurotropic human herpesviruses. The association between serologic evidence of herpesvirus infection and cognitive functioning was analyzed by univariate analyses, as well as multivariate analyses that included demographic and clinical factors associated with cognitive functioning., Results: Serologic evidence of infection with herpes simplex virus type 1 was an independent predictor of decreased cognitive functioning in the individuals with bipolar disorder (F = 20.5, p <.0001). Discriminant function analysis indicated that most of the difference in cognitive functioning between individuals who were antibody positive and antibody negative for herpes simplex virus type 1 could be attributed to immediate verbal memory (F = 12.07, p <.001). There was no significant association between cognitive functioning and the other human herpesviruses. No association between antibodies to herpesviruses and cognitive functioning was found in the control individuals without a history of psychiatric disorder., Conclusions: Serologic evidence of herpes simplex virus type 1 infection is associated with cognitive impairment in individuals with bipolar disorder.

Background/aims: Hepatitis C has been associated with a decrease in quality of life and with neurological abnormalities. The aim of our study was to investigate the relationship between quality of life and cognitive function., Methods: Quality of life, clinical variables and neuropsychological function were evaluated in 120 patients with hepatitis C (mild chronic hepatitis, compensated cirrhosis and decompensated cirrhosis) and in healthy controls (n=40, in each group)., Results: Patients with chronic hepatitis or compensated cirrhosis showed a decrease in quality of life, in spite of unimpaired neuropsychological tests. Patients with decompensated cirrhosis exhibited a further decrease in quality of life and neuropsychological abnormalities. The decrease in quality of life was associated with the severity of liver failure, neuropsychological abnormalities and treatment with beta-blockers or diuretics. However, in the multivariable analysis, only treatment with beta-blockers or diuretics (which was limited to decompensated cirrhosis) was independently associated with quality of life., Conclusions: Hepatitis C causes a decrease in quality of life even in the absence of major cognitive impairment. The mechanisms that worsen quality of life are unknown. However, in cirrhotic outpatients with prior decompensations, treatment with beta-blockers or diuretics appears to have an important effect on quality of life.

Background/aims: Central nervous system abnormalities such as fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in many other causes of chronic liver disease. The finding that fatigue is unrelated to activity of hepatitis or mode of infection could indicate an independent effect of HCV on brain function. This study tested the hypothesis of a subclinical cognitive dysfunction in HCV-infected patients., Methods: One-hundred untreated HCV-RNA positive biopsy-proven patients were investigated by P300 event-related potentials, a sensitive electrophysiologic test of cognitive processing. Health-related quality of life and fatigue were assessed using the SF-36 questionnaire and the Fatigue Impact Scale, respectively., Results: Cognitive brain function was subclinically impaired in the cohort of HCV-infected patients as indicated by significantly prolonged P300 latencies (P=0.01 for comparison to matched healthy subjects) and reduced P300 amplitudes (P<0.001, respectively). Seventeen of the 100 HCV-infected patients had P300 latencies outside the age-adjusted normal range. Abnormal P300 characteristics were not related to the degree of histologic or biochemical activity of hepatitis, severity of fatigue or mental health impairment., Conclusions: This study demonstrates that patients with HCV infection showed a slight but significant neurocognitive impairment, possibly indicating a further extrahepatic manifestation of chronic hepatitis C.