Subtype associations with HIV-associated neurocognitive disorder in China

Factors associated with HIV-associated neurocognitive disorders (HAND) include CD4⁺ nadir and count, HIV RNA level, and HIV-1 subtype. Here, we investigated demographical and clinical markers with respect to HAND in a homogenous Chinese population. Individuals with HAND (global deficit score ≥0.5) had lower nadir (p?<?0.01) and CD4⁺ counts (p?=?0.03). HAND was also associated with AIDS (p?<?0.01), but subtype was not (p?=?0.198). Furthermore, worse impairment correlated with higher viral diversity (r?=?0.16, p?<?0.01), lower nadir (r?=??0.17, p?<?0.01), and CD4⁺ counts (r?=??0.11, p?=?0.01). These remained significant even when correcting for subtype. Our findings suggest that subtype does not have a major impact on HAND.     

Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China

In the current era of highly active antiretroviral therapy (HAART), the incidence of HIV dementia has declined, but the prevalence of HIV-associated neurocognitive disorder (HAND) remains high. HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND. Changes in cytokine levels in the cerebrospinal fluid (CSF) during HIV infection might help to identify HAND. To investigate whether the cytokine profile of the CSF during HIV infection could be used as a biomarker of HAND, we compared cytokine levels in the CSF of HIV-infected cases with and without neurocognitive impairment. Cytokine concentrations in the CSF were measured by quantification bioassays (Luminex xMAP). HIV-infected cases with neurocognitive impairment demonstrated higher levels of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, induced protein (IP)-10, and granulocyte colony-stimulating factor (G-CSF) in the CSF than those without neurocognitive impairment (G-CSF (p?=?0.0003), IL-8 (p?=?0.0046), IP-10 (p?<?0.0001), and MCP-1 (p?<?0.0001)). There was no significant impact of HAART on cytokine levels in the CSF, except for IP-10, which was higher in HAART-treated patients with impaired cognition (p?=?0.0182). Findings from this preliminary study suggest that elevated levels of the cytokines IL-8, MCP-1, G-CSF, and IP-10 in the CSF are associated with neurocognitive impairment in HIV infection, and these cytokines likely represent a biomarker profile for HAND.     

Preliminary study of a novel cognitive assessment device for the evaluation of HIV-associated neurocognitive impairment

Given the high prevalence of HIV-associated neurocognitive disorders (HAND), we examined the performance of a novel computerized cognitive assessment device (NCAD) for the evaluation of neurocognitive impairment in the setting of HIV. In addition to a standard 8-test neuropsychological battery, each participant underwent testing with the NCAD, which requires approximately 20 min and has been shown to accurately measure neurocognition in elderly individuals. The NCAD yields seven subtest scores in addition to an overall predictive score that is calculated based on subtest results. Thirty-nine HIV-infected participants were included in this study; the majority of which (71.8 %) had undetectable plasma HIV RNA levels and a history of significant immunocompromise (median nadir CD4+ count 34 cells/μl). The mean composite neuropsychological score (NPT-8) was 46.07, and mean global deficit score (GDS) was 0.59. NCAD total subtest accuracy correlated significantly with NPT-8 (Pearson correlation r?=?0.59, p?<?0.0001) as well as GDS (Spearman’s rho?=??0.36, p?=?0.02). NCAD predictive score also correlated significantly with NPT-8 (Spearman’s rho?=??0.5601, p?=?0.0016) and GDS (Spearman’s rho?=?0.45, p?=?0.0144). When using the most recent nosology of HAND criteria for neurocognitive impairment, the area under the curve (AUC) for NCAD total subtest accuracy was 0.7562 (p?=?0.012), while the AUC for the HIV dementia scale was 0.508 (p?=?0.930). While not as comprehensive as a full neuropsychological battery, the NCAD shows promise as a rapid screening tool for HIV-infected individuals, and additional research of this device is indicated.     

Physical exercise is associated with less neurocognitive impairment among HIV-infected adults

Neurocognitive impairment (NCI) remains prevalent in HIV infection. Randomized trials have shown that physical exercise improves NCI in non-HIV-infected adults, but data on HIV-infected populations are limited. Community-dwelling HIV-infected participants (n?=?335) completed a comprehensive neurocognitive battery that was utilized to define both global and domain-specific NCI. Participants were divided into “exercise” (n?=?83) and “no exercise” (n?=?252) groups based on whether they self-reported engaging in any activity that increased heart rate in the last 72 h or not. We also measured and evaluated a series of potential confounding factors, including demographics, HIV disease characteristics, substance use and psychiatric comorbidities, and physical functioning. Lower rates of global NCI were observed among the exercise group (15.7 %) as compared to those in the no exercise group (31.0 %; p?<?0.01). A multivariable logistic regression controlling for potential confounds (i.e., education, AIDS status, current CD4+ lymphocyte count, self-reported physical function, current depression) showed that being in the exercise group remained significantly associated with lower global NCI (odds ratio?=?2.63, p?<?0.05). Similar models of domain-specific NCI showed that exercise was associated with reduced impairment in working memory (p?<?0.05) and speed of information processing (p?<?0.05). The present findings suggest that HIV-infected adults who exercise are approximately half as likely to show NCI as compared to those who do not. Future longitudinal studies might be best suited to address causality, and intervention trials in HIV-infected individuals will determine whether exercise can prevent or ameliorate NCI in this population.     

Post-traumatic stress is associated with verbal learning,memory, and psychomotor speed in HIV-infected and HIV-uninfected women

The prevalence of post-traumatic stress disorder (PTSD) is higher among HIV-infected (HIV+) women compared with HIV-uninfected (HIV?) women, and deficits in episodic memory are a common feature of both PTSD and HIV infection. We investigated the association between a probable PTSD diagnosis using the PTSD Checklist-Civilian (PCL-C) version and verbal learning and memory using the Hopkins Verbal Learning Test in 1004 HIV+ and 496 at-risk HIV? women. HIV infection was not associated with a probable PTSD diagnosis (17 % HIV+, 16 % HIV?; p?=?0.49) but was associated with lower verbal learning (p?<?0.01) and memory scores (p?<?0.01). Irrespective of HIV status, a probable PTSD diagnosis was associated with poorer performance in verbal learning (p?<?0.01) and memory (p?<?0.01) and psychomotor speed (p?<?0.001). The particular pattern of cognitive correlates of probable PTSD varied depending on exposure to sexual abuse and/or violence, with exposure to either being associated with a greater number of cognitive domains and a worse cognitive profile. A statistical interaction between HIV serostatus and PTSD was observed on the fine motor skills domain (p?=?0.03). Among women with probable PTSD, HIV? women performed worse than HIV+ women on fine motor skills (p?=?0.01), but among women without probable PTSD, there was no significant difference in performance between the groups (p?=?0.59). These findings underscore the importance of considering mental health factors as correlates to cognitive deficits in women with HIV.     

Older individuals with HIV infection have greater memory deficits than younger individuals

The prevalence of HIV-associated neurocognitive disorder (HAND) remains persistently high in the era of combination antiretroviral therapy. We aimed to characterize the pattern of neurocognitive dysfunction in older subjects with HAND in particular amnestic versus non-amnestic impairment. One hundred six subjects from the Johns Hopkins University NIMH Clinical Outcomes cohort underwent standardized neuropsychological (NP) testing between November 2006 and June 2010. We examined performance in seven cognitive domains (memory, attention, speed of processing, visuospatial, language, motor, and executive). Older subjects were defined as age >50 years at the time of NP testing. Subjects were diagnosed with HAND according to established criteria and dichotomized into amnestic cognitive impairment or non-amnestic cognitive impairment with deficit defined as z scores <?1.5 for the verbal and nonverbal memory domains. There were 32 older subjects with a mean age (SD) of 54.2 (2.8)?years and 74 younger subjects, 43.7 (4.3)?years. Older age was associated with a 4.8-fold higher odds of memory deficits adjusted for potential confounders (p?=?0.035) identified a priori. With age modeled as a continuous covariate, every 1 year increase in age was associated with a 1.11-fold higher odds of memory deficit (p?=?0.05). There was a higher proportion of amnestic cognitive impairment among older subjects than younger subjects with HIV infection. Neurodegenerative processes other than those directly due to HIV may be increasingly important as individuals with chronic HIV infection and HAND survive into older age.     

Impact of human immunodeficiency virus on neurocognition and risky behaviors in young adults

Previous studies have identified cognitive impairments due to human immunodeficiency virus (HIV) in adults. However, few studies have examined the impact of HIV on cognition in young adults (18–24 years old). Yet, this group is one of the largest populations of individuals with new HIV infection. Young adulthood is also an important developmental window because the brain has not fully matured and individuals are prone to engage in risky behavior. The purpose of the present study was to examine the impact of HIV on neurocognition and risky behaviors. We hypothesized that HIV+ young adults (n?=?23) would exhibit greater cognitive impairment and risky behaviors compared to seronegative controls (n?=?21). In addition, we predicted that self-reported risky behavior as assessed by the Risk Assessment Battery (RAB) would covary with cognitive performances. Results revealed poorer executive function in HIV+ young adults compared to seronegative (HIV?) controls. HIV+ young adults exhibited significantly greater risk scores on the RAB (p?相似文献   

Neurocognitive functioning among HIV-positive adults in southern India

The validity of a comprehensive international neuropsychological (NP) test battery for detection of HIV-associated neurocognitive disorders (HAND) in a Tamil speaking southern Indian cohort (69 HIV+ and 67 HIV?) was explored. The prevalence of HAND was significantly higher in the HIV+ vs. HIV? group (33 vs.13%; p < 0.01). Impairment rates were highest in the motor and speed of information processing domains. An NP battery translated into Tamil appears to be a valid tool for assessing HAND because the prevalence it found of HAND in southern India is similar to that found elsewhere.     

Central nervous system antiretroviral penetration and cognitive functioning in largely pretreated HIV-infected patients

Prolonged time on effective antiretroviral therapy (ART) should be associated with a low incidence of neurocognitive impairment (NCI). We investigated the rate of NCI in 162 largely pretreated patients with HIV RNA suppression according to CNS antiretroviral drug penetration in comparison with 67 patients on their first ART line. Cognitive performance (Trailmaking A, B, Digit Symbol, Grooved Pegboard; demographically adjusted and converted to Z scores, NPZ4) was evaluated, and CNS penetration effectiveness (CPE) ranks of 1 to 4 were assigned and summed per regimen. After a median of 173.2 months on therapy (1,909.3 patients-year), the rate of NCI was similar in both groups (mean NPZ4, ?0.24 vs ?0.2). Pretreated patients received regimens with a CPE <7 in a large proportion (30 vs 9 %; p?<?0.01). Patients in monotherapy had worse NPZ4 score than patients receiving triple therapy (?0.78 vs ?0.18; p?=?0.02; effect sizes 1.38), and a lower CPE score was observed in patients with a CD4+ count nadir <200 cells/ml with NCI (6.5 vs 7.3, p?=?0.04). In the multivariate model, only the lowest CD4+ count and hepatitis C virus coinfection were associated with NPZ4, whereas CPE <7 showed a trend to association (p?=?0.06) probably due to patients on monotherapy (estimate ?0.33, p?<?0.01). In conclusion, the rate of NCI in largely pretreated patients was similar to that observed in patients on their first regimen, and nadir CD4+ count continue to be critical. CNS drug penetration should be considered in cases of high risk for NCI.     

HIV-associated neurocognitive disorder in Australia: a case of a high-functioning and optimally treated cohort and implications for international neuroHIV research

The Australian HIV-infected (HIV+) population is largely comprised of high-functioning men who have sex with men (MSM). Like other English-speaking countries, Australia mostly relies on US neuropsychological normative standards to detect and determine the prevalence of neurological disorders. Whether the US neuropsychological (NP) normative standards are appropriate in Australian HIV+ MSM has not been established. Ninety virally suppressed HIV+ and 49 HIV-uninfected (HIV?) men (respectively 86 and 85 % self-reported MSM; mean age 54 and 56 years, mean premorbid verbal IQ estimate 110 and 111) undertook standard NP testing. The raw neuropsychological data were transformed using the following: (1) US standards as uncorrected scaled scores and demographically corrected T scores (US norms); and (2) z scores (without demographic corrections) derived from Australian comparison group scaled scores (local norms). To determine HIV-associated neurocognitive disorder prevalence, we used a standard definition of impairment based upon a battery-wide summary score: the global deficit score (GDS). Impairment classification (GDS?≥?0.5) based on the local norms was best at discriminating between the two groups (HIV??=?14.3 % vs. HIV+?=?53.3 %; p?<?0.0001). This definition was significantly associated with age. Impairment classification based on the US norms yielded much lower impairment rate regardless of the HIV status (HIV??=?4.1 % vs. HIV+?=?14.7 %; p?=?0.05), but was associated with historical AIDS, and not age. Both types of summary scores were associated with reduced independence in activities of daily living (p?≤?0.03). Accurate neuropsychological classifications of high (or low) functioning individuals may need country-specific norms that correct for performance-based (e.g., reading) estimates of premorbid cognition in addition to the traditional demographic factors.     

HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV?) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV ? participants from the pre-CART era (1988–1995; N?=?857) and CART era (2000–2007; N?=?937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.     

Screening for neurocognitive impairment in HIV-positive adults aged 50 years and older: Montreal Cognitive Assessment relates to self-reported and clinician-rated everyday functioning

As the HIV+ population ages, the risk for and need to screen for HIV-associated neurocognitive disorders (HAND) increases. The aim of this study is to determine the utility and ecological validity of the Montreal Cognitive Assessment (MoCA) among older HIV+ adults. A total of 100 HIV+ older adults aged 50 years or over completed a comprehensive neuromedical and neurocognitive battery, including the MoCA and several everyday functioning measures. The receiver operating characteristic curve indicates ≤26 as the optimal cut-off balancing sensitivity (84.2%) and specificity (55.8%) compared to “gold standard” impairment as measured on a comprehensive neuropsychological battery. Higher MoCA total scores are significantly (p < .01) associated with better performance in all individual cognitive domains except motor abilities, with the strongest association with executive functions (r = ?0.49, p < .01). Higher MoCA total scores are also significantly (p <.01) associated with fewer instrumental activities of daily living declines (r = ?0.28), fewer everyday cognitive symptoms (r = ?0.25), and better clinician-rated functional status (i.e., Karnofsky scores; r = 0.28); these associations remain when controlling for depressive symptoms. HIV+ individuals who are neurocognitively normal demonstrate medium-to-large effect size differences in their MoCA performance compared to those with asymptomatic neurocognitive impairment (d = 0.85) or syndromic HAND (mild neurocognitive disorder or HIV-associated dementia; d = 0.78), while the latter two categories do not differ. Although limited by less than optimal specificity, the MoCA demonstrates good sensitivity and ecological validity, which lends support to its psychometric integrity as a brief cognitive screening tool among older HIV+ adults.     

Detrimental impact of remote methamphetamine dependence on neurocognitive and everyday functioning in older but not younger HIV+ adults: evidence for a legacy effect?

Prior studies examining the combined adverse effects of HIV and methamphetamine (MA) on the central nervous system (CNS) have focused on younger to middle-aged adults with recent MA use diagnoses. Aging, HIV, and MA all converge on prefrontal and temporolimbic neural systems and confer independent risk for neurocognitive and functional decline. Thus, this study sought to determine the residual impact of a remote history of MA dependence on neurocognitive and real-world outcomes in older people living with HIV (PLWH). Participants included 116 older (≥50 years) and 94 younger (<40 years) adults classified into one of six study groups based on HIV serostatus (HIV+/HIV?) and lifetime histories of MA dependence (MA+/MA?): older HIV?MA? (n?=?36), older HIV+MA? (n?=?49), older HIV+MA+ (n?=?31), younger HIV?MA? (n?=?27), younger HIV+MA? (n?=?33), and younger HIV+MA+ (n?=?34). No participant-met criteria for current MA use disorders and histories of MA dependence were remote in both the older (average of nearly 9 years prior to evaluation) and younger (average of over 2 years prior to evaluation) HIV+MA+ groups. Findings revealed that a remote history of MA dependence exerts a significant detrimental impact on specific aspects of neurocognitive performance (e.g., memory) and a broad range of real-world functioning outcomes (e.g., employment) among older, but not younger PLWH. These results suggest that MA-associated neurotoxicity may have significant “legacy” effects on both neurocognitive and functional outcomes to which older PLWH are particularly vulnerable.     

Suicide risk and prevalence of major depressive disorder (MDD) among individuals infected with HIV-1 subtype C versus B in Southern Brazil

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV? and higher in HIV subtype B compared with C. Individuals with HIV (n?=?39) as well as seronegative controls (n?=?22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV? group: current MDD, 15 (38.5 %) vs. 0 (0 %), p?=?0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p?=?0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV? (13 (8–27.5) vs. 2.5 (1–5.5); p?<?0.0001). Current suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p?=?0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV?. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C.     

Risky decision-making in HIV-associated neurocognitive disorders (HAND)

Individuals infected with HIV show moderate deficits in decision-making, but the ecological relevance of such deficits on everyday functioning has not previously been described. This study sought to examine the magnitude, cognitive correlates, and everyday functioning impact of risky decision-making impairment in HIV-associated neurocognitive disorders (HAND). Participants included 68?HIV+ individuals with HAND, 78?HIV+ individuals without HAND, and 51?HIV? comparison participants, who were administered the Iowa Gambling Task (IGT) alongside a comprehensive neuropsychological test battery and self-report measures assessing aspects of everyday functioning. HIV+ individuals with HAND performed more poorly on the IGT relative to the other two groups, most notably during the last three trial blocks. Within the HIV+ group, IGT performance during the last three trial blocks was most strongly associated with cognitive flexibility, but was not significantly related to declines in instrumental activities of daily living (IADLs), unemployment, or medication non-adherence. While overall IGT performance across the last three trial blocks may be helpful diagnostically in identifying decision-making impairment in HAND, examination of alternate, more specific metrics (e.g., individual deck selections across trial blocks) may be more useful in delineating the role of poor decision-making in HIV-related disability, and should be examined in future research.     

Relevance of lipopolysaccharide levels in HIV-associated neurocognitive impairment: the Neuradapt study

Contributory factors to HIV-associated neurocognitive disorders (HAND) have been shown to include age, co-morbid infections, medication toxicity, virological, genetic and vascular mechanisms, as well as microbial translocation of lipopolysaccharide (LPS), which is suspected to trigger monocyte activation and increase trafficking of infected cells into the brain. In this study, our aim was to assess the degree of neurocognitive impairment in a group of randomly selected HIV-infected patients and investigate potential risk factors, including LPS plasma levels. Furthermore, we evaluated the relevance of LPS as a potential marker for screening patients with mild neurocognitive impairment. LPS plasma levels were compared among patients with HAND and those with no HAND. As LPS has also been shown to be elevated in hepatitis C co-infection, the analysis was stratified according to the presence or not of hepatitis C virus (HCV) co-infection. Differences between groups were evaluated using chi-square tests and Kruskal–Wallis non-parametric tests. Stepwise logistic regression was performed to identify independent risk factors for HAND in the subgroups of HCV-positive and negative patients. A p value <0.05 was considered significant. Analyses were conducted using SPSS® software. From December 2007 to July 2009, 179 patients were tested (mean age 44, 73 % male, 87 % on treatment, 30 % HCV co-infected, median CD4 504/ml and 67 % with viral load below 40 copies/ml). HAND was identified in 40/179 patients (22 %), the majority displaying asymptomatic neurocognitive impairment or mild neurocognitive disorder. Univariate analysis showed that age, illicit drug use, hepatitis C co-infection, prior AIDS-defining events, CD4/CD8 ratio and LPS plasma levels were significantly associated with HAND. The median LPS level was 98.2 pg/ml in the non-HAND group versus 116.1 pg/ml in the HAND group (p?<?0.014). No differences were found in LPS values between subgroups of impairment. There was a clear association between LPS levels and HAND in the HCV-positive group (p?=?0.036), while there was none in the HCV-negative group (p?=?0.502). No difference in degree of hepatic fibrosis was found between the HAND and non-HAND groups. In conclusion, LPS levels were associated with HAND in the HCV-positive group, while, in the HCV-negative group, age and pro-viral DNA were the only variables independently associated with HAND. There was no difference in degree of liver disease as predicted by score of fibrosis between HAND and non-HAND groups. The role of HCV co-infection and higher LPS levels in the pathogenesis of HAND in patients with viral suppression on treatment requires further investigation.     

A comparison of performance-based measures of function in HIV-associated neurocognitive disorders

The objectives of this study are to compare the results of newer performance-based functional assessments in the study of HIV-associated neurocognitive disorders (HAND) and to correlate these functional assessments with specific levels of severity of HAND. One hundred fourteen HIV+ subjects in an existing cohort were evaluated with a medical history, neurological exam, neuropsychological test battery as well as subjective and novel objective measures of functional abilities. Self-reported measures of functional performance included the Karnofsky Performance Scale, a questionnaire for instrumental activities of daily living, and a questionnaire for physical quality of life measures. The newer objective functional performance assessments included the Columbia Medication Management and the San Diego Finances tests. These newer performance-based measures of function were assessed for their ability to predict level of HAND. The two objective measures of functional performance, The Columbia Medication Management Scale and the San Diego Finances Test, were both associated with levels of severity of HAND. The Karnofsky Performance Scale and the questionnaires for role and physical quality of life were subjective measures that were also associated with specific levels of HAND. Newer measures of functional performance can be used to objectively evaluate functional impairment in HAND and validate different levels of HAND.     

Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection

Crack cocaine use is associated with impaired verbal memory in HIV-infected women more than uninfected women. To understand the neural basis for this impairment, this study examined the effects of crack cocaine use on activation of the prefrontal cortex (PFC) and strategic encoding during a verbal memory task in HIV-infected women. Three groups of HIV-infected women from the Chicago Consortium of the Women’s Interagency HIV Study were compared: current users of crack cocaine (n?=?10), former users of cocaine (n?=?11), and women who had never used cocaine (n?=?9). Participants underwent functional magnetic resonance imaging during a verbal memory task and completed a neuropsychological test of verbal memory. On the neuropsychological test, current crack users performed significantly worse than other groups on semantic clustering, a measure of strategic encoding, p?<?0.05. During encoding, activation in left anterior cingulate cortex (ACC) was lower in current and former cocaine users compared to never users. During recognition, activation in bilateral PFC, specifically left dorsal medial PFC and bilateral dorsolateral PFC, was lower in current and former users compared to women who had never used cocaine. Lower activation in left dorsolateral PFC was correlated with worse performance on the recognition task, p?<?0.05. The verbal learning and memory deficits associated with cocaine use in women with HIV may be partially accounted for by alterations in ACC and PFC function.     

Permanent muscular sodium overload and persistent muscle edema in Duchenne muscular dystrophy: a possible contributor of progressive muscle degeneration

To assess the presence and persistence of muscular edema and increased myoplasmic sodium (Na⁺) concentration in Duchenne muscular dystrophy (DMD). We examined eight DMD patients (mean age 9.5?±?5.4?years) and eight volunteers (mean age 9.5?±?3.2?years) with 3-tesla proton (¹H) and ²³Na density-adapted 3D-radial MR sequences. Seven DMD patients were re-examined about 7?months later without change of therapy. The eighth DMD patient was re-examined after 5 and 11?months under medication with eplerenone. We quantified muscle edema on STIR images with background noise as reference and fatty degeneration on T1-weighted images using subcutaneous fat as reference. Na⁺ was quantified by a muscular tissue Na⁺ concentration (TSC) sequence employing a reference containing 51.3?mM Na⁺ with 5?% agarose. With an inversion-recovery (IR) sequence, we determined mainly the myoplasmic Na⁺. The normalized muscular ²³Na IR signal intensity was higher in DMD than in volunteers (n?=?8, 0.75?±?0.07 vs. 0.50?±?0.05, p?<?0.001) and persisted at second measurement (n?=?7, 1st 0.75?±?0.07, 2nd 0.73?±?0.06, p?=?0.50). When compared to volunteers (25.6?±?2.0?mmol/l), TSC was markedly increased in DMD (38.0?±?5.9?mmol/l, p?<?0.001) and remained constant (n?=?7, 1st 37.9?±?6.4?mmol/l, 2nd 37.0?±?4.0?mmol/l, p?=?0.49). Muscular edema (15.6?±?3.5 vs. 6.9?±?0.7, p?<?0.001) and fat content (0.48?±?0.08 vs. 0.38?±?0.01, p?=?0.003) were elevated in DMD when compared to volunteers. This could also be confirmed during follow-up (n?=?7, p?=?0.91, p?=?0.12). Eplerenone slightly improved muscle strength and reduced muscular sodium and edema. The permanent muscular Na⁺ overload in all DMD patients is likely osmotically relevant and responsible for the persisting, mainly intracellular muscle edema that may contribute to the progressive muscle degeneration.     

Neurocognitive impairment in HIV-1 clade C- versus B-infected individuals in Southern Brazil

HIV-1 clade C isolates show reduced Tat protein chemoattractant activity compared with clade B. This might influence neuropathogenesis by altering trafficking of monocytes into the CNS. A previous study suggested low rates of HIV-associated dementia in clade C-infected individuals. The present study evaluated neurocognitive impairment rates in clade B- and C-infected individuals from the same local population. HIV+ and HIV? participants were recruited from the same geographic region in Southern Brazil. We evaluated neuropsychological (NP) impairment using a screening instrument (the International HIV Dementia Scale (IHDS)), as well as a Brazilian Portuguese adaptation of a comprehensive battery that has demonstrated sensitivity to HIV-associated neurocognitive disorders (HAND) internationally. NP performance in controls was used to generate T scores and impairment ratings by the global deficit score (GDS) method. Clade assignments were ascertained by sequencing pol and env. Blood and cerebrospinal fluid were collected from all HIV+ participants. HIV+ and HIV? participants were comparable on demographic characteristics. HIV+ participants overall were more likely to be impaired than HIV? by the IHDS and the GDS. Clade B- and C-infected individuals were demographically similar and did not differ significantly in rates of impairment. The prevalence of pleocytosis, a marker of intrathecal cellular chemotaxis, also did not differ between clade B and C infections. Clade B and C HIV-infected individuals from the same geographic region, when ascertained using comparable methods, did not differ in their rates of neurocognitive impairment, and there was no evidence of differences in CNS chemotaxis.