Fibroblast growth factors 1 and 2 in cerebrospinal fluid are associated with HIV disease, methamphetamine use, and neurocognitive functioning.

BackgroundHuman immunodeficiency virus (HIV) and methamphetamine use commonly affect neurocognitive (NC) functioning. We evaluated the relationships between NC functioning and two fibroblast growth factors (FGFs) in volunteers who differed in HIV serostatus and methamphetamine dependence (MAD).MethodsA total of 100 volunteers were categorized into four groups based on HIV serostatus and MAD in the prior year. FGF-1 and FGF-2 were measured in cerebrospinal fluid by enzyme-linked immunosorbent assays along with two reference biomarkers (monocyte chemotactic protein [MCP]-1 and neopterin). Comprehensive NC testing was summarized by global and domain impairment ratings.ResultsSixty-three volunteers were HIV+ and 59 had a history of MAD. FGF-1, FGF-2, and both reference biomarkers differed by HIV and MAD status. For example, FGF-1 levels were lower in subjects who had either HIV or MAD than in HIV- and MAD- controls (P=0.003). Multivariable regression identified that global NC impairment was associated with an interaction between FGF-1 and FGF-2 (model R(2)=0.09, P=0.01): higher FGF-2 levels were only associated with neurocognitive impairment among subjects who had lower FGF-1 levels. Including other covariates in the model (including antidepressant use) strengthened the model (model R(2)=0.18, P=0.004) but did not weaken the association with FGF-1 and FGF-2. Lower FGF-1 levels were associated with impairment in five of seven cognitive domains, more than FGF-2, MCP-1, or neopterin.ConclusionThese findings provide in vivo support that HIV and MAD alter expression of FGFs, which may contribute to the NC abnormalities associated with these conditions. These cross-sectional findings cannot establish causality and the therapeutic benefits of recombinant FGF-1 need to be investigated

Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria.

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes

HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score

This literature review summarizes the existing research examining the CNS penetration effectiveness (CPE) score and neurocognitive outcomes (i.e., neuropsychological assessment and neurocognitive screening) in HIV+ individuals. Despite the effectiveness of Combined Antiretroviral Therapy (CART) in reducing mortality and morbidity in HIV and controlling viral replication, HIV often persists in the Central Nervous System (CNS), and rates of neurocognitive impairment remain higher than predicted in the post-CART era. The CPE score was developed to rank antiretroviral regimens on their ability to penetrate the CNS and potency in inhibiting the virus, and it has been examined in relation to neurocognitive functioning for over a decade. Based on the results of 23 studies, we conclude that CPE is not as strongly associated with neurocognitive outcomes as initially hypothesized, although higher CPE ARV regimens may be associated with modest, improved outcomes in global neurocognitive functioning, and to a lesser extent attention/working memory and learning/memory. Conclusions, however, are limited by the heterogeneity in study design and methods, and the lack of a more recent CPE metric update. It is recommended that future research in this area employ comprehensive, standardized neuropsychological test batteries and examine domain-level performance, and use the newer 2010 CPE metric, although an updated CPE ranking is urgently needed

Assessing Neuropsychological Performance in a Migrant Farm Working Colonia in Baja California, Mexico: A Feasibility Study

Neuropsychological impairments (NPI) can lead to difficulties in daily functioning and ultimately contribute to poor health outcomes. However, evidence for the feasibility of NPI assessment in resource-limited settings using tests developed in high literacy/high education cultures is sparse. The main objectives were to: (1) determine the feasibility and appropriateness of conducting neuropsychological assessments among a migrant farm worker population in Baja California, Mexico and (2) preliminary describe neuropsychological test performance in this unique population. A neuropsychological test battery was administered to 21 presumably healthy adults (8 men, 13 women) during a two-day international health services and research collaboration. All but one neuropsychological test (i.e. figure learning) was feasible and appropriate to administer to the study population. Contrary to expectations, participants performed better on verbal rather than nonverbal neuropsychological tests. Results support inclusion of neuropsychological tests into future studies among migrant farm worker populations in Baja California, Mexico

Effects of HIV and childhood trauma on brain morphometry and neurocognitive function.

A wide spectrum of neurocognitive deficits characterises HIV infection in adults. HIV infection is additionally associated with morphological brain abnormalities affecting neural substrates that subserve neurocognitive function. Early life stress (ELS) also has a direct influence on brain morphology. However, the combined impact of ELS and HIV on brain structure and neurocognitive function has not been examined in an all-female sample with advanced HIV disease. The present study examined the effects of HIV and childhood trauma on brain morphometry and neurocognitive function. Structural data were acquired using a 3T Magnetom MRI scanner, and a battery of neurocognitive tests was administered to 124 women: HIV-positive with ELS (n = 32), HIV-positive without ELS (n = 30), HIV-negative with ELS (n = 31) and HIV-negative without ELS (n = 31). Results revealed significant group volumetric differences for right anterior cingulate cortex (ACC), bilateral hippocampi, corpus callosum, left and right caudate and left and right putamen. Mean regional volumes were lowest in HIV-positive women with ELS compared to all other groups. Although causality cannot be inferred, findings also suggest that alterations in the left frontal lobe, right ACC, left hippocampus, corpus callosum, left and right amygdala and left caudate may be associated with poorer neurocognitive performance in the domains of processing speed, attention/working memory, abstraction/executive functions, motor skills, learning and language/fluency with these effects more pronounced in women living with both HIV and childhood trauma. This study highlights the potential contributory role of childhood trauma to brain alterations and neurocognitive decline in HIV-infected individuals

Neurocognitive impairment is worse in HIV/HCV-coinfected individuals with liver dysfunction

Infections with HIV and hepatitis C virus (HCV) can individually and jointly contribute to neurocognitive impairment (NCI). Rates of NCI in HIV/HCV-coinfected persons range from 40 to 63% but its correlates have not been described. In this study, we examined HIV/HCV-coinfected adults on antiretroviral therapy (ART) with undetectable HIV RNA in blood (n = 412) who were assessed using a comprehensive neuropsychological test battery. Demographics, host and viral biomarkers, and markers of liver dysfunction were compared between impaired (n = 198) and unimpaired (n = 214) participants using logistic regression. The cohort was predominantly middle-aged men, half of whom (48%) had NCI. The odds of NCI increased by almost two-fold when serum albumin was < 4 g/dL, 1.7-fold when alanine aminotransferase (ALT) levels were > 50 IU/L, and 2.2-fold with every unit increase in log10 AST to Platelet Ratio Index (APRI). These readily available clinical biomarkers of NCI measure hepatic injury and/or dysfunction, suggesting a mechanism for the effects of HCV infection on NCI. They may identify patients at increased risk of NCI who could be prioritized for early initiation of HCV treatment to protect or improve cognition

Cannabis use is associated with greater total sleep time in middle-aged and older adults with and without HIV: A preliminary report utilizing digital health technologies.

Current literature on the effect of cannabis use on sleep quality is mixed, and few studies have used objectively-measured sleep measures or real-time sampling of cannabis use to examine this relationship. The prevalence of cannabis use among older adults and persons living with HIV has increased in recent years, and poor sleep quality is elevated in these populations as well. However, research examining cannabis-sleep relationships in these populations is lacking. Thus, we aimed to examine the relationship between daily cannabis use and subsequent objectively-measured sleep quality in middle-aged and older adults with and without HIV. In this pilot study, seventeen (11 HIV+, 6 HIV-) adults aged 50-70 who consumed cannabis completed four daily smartphone-based surveys for 14 days, in which they reported their cannabis use (yes/no) since the last survey. Participants also wore actigraphy watches during the 14-day period to objectively assess sleep quality (i.e., efficiency, total sleep time, and sleep fragmentation). In linear mixed-effects models, cannabis use was significantly associated with greater subsequent total sleep time (β=0.56; p=0.046). Cannabis use was not related to a change in sleep efficiency (β=1.50; p=0.46) nor sleep fragmentation (β=0.846, p=0.756) on days with cannabis use versus days without cannabis use. These preliminary results indicate cannabis use may have a positive effect on sleep duration in middle-aged and older adults. However, future studies with larger sample sizes that assess cannabis use in more detail (e.g., route of administration, dose, reason for use) are needed to further understand this relationship

Second-language fluency predicts native language stroop effects: evidence from Spanish-English bilinguals.

Studies have shown reduced Stroop interference in bilinguals compared to monolinguals defined dichotomously, but no study has explored how varying degrees of second language fluency, might affect linguistic inhibitory control in the first language. We examined effects of relative English fluency on the ability to inhibit the automatic reading response on the Golden version of the Stroop Test administered in Spanish. Participants were 141 (49% male) adult native Spanish speakers from the U.S.-Mexico border region (education range = 8-20 and age range = 20-63). A language dominance index was calculated as the ratio of English words to total words produced in both languages using the Controlled Oral Word Association Test with letters PMR in Spanish and FAS in English. Greater degree of English fluency as measured by the dominance index predicted better speed on the Stroop incongruent trial independent of education effects. On the other hand, neither the dominance index nor education predicted performance on the word reading and color-naming trials. These results suggest an advantage in inhibitory control among those with greater second-language ability