Limited correlation between systemic biomarkers and neurocognitive performance before and during HIV treatment

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = − 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = − 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.     

Plasma CXCL10 correlates with HAND in HIV-infected women

HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV-infected (HIV+) young adults, parenterally infected during early childhood. One hundred forty-four HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1β, IL-6, CCL2, CXCL8, CXCL10, and TNF-α were measured in plasma in all participants and in cerebrospinal fluid (CSF) in a subgroup of 56 study participants. Biomarkers were compared with neurocognitive outcomes, and the influence of sex and HIV disease biomarkers was assessed. In this cohort of young adults (median age of 24 years), the rate of neurocognitive impairment (NCI) was 36.1%. Median current CD4+ count was 479 cells/mm3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma, controlling for sex, higher levels of IL-6 and TNF-α were associated with NCI (p < 0.05). Plasma CXCL10 showed a significant interaction with sex (p = 0.02); higher values were associated with NCI in women only (p = 0.02). Individuals with undetectable viral load had significantly lower plasma CXCL10 (p < 0.001) and CCL2 (p = 0.02) levels, and CSF CXCL10 (p = 0.01), IL-6 (p = 0.04), and TNF-α (p = 0.04) levels. NCI in young men and women living with HIV was associated with higher IL-6 and TNF-α in plasma, but not in the CSF. CXCL10 was identified as a biomarker of NCI specifically in women with chronic HIV infection.     

Cognitive impairment and CSF proteome modification after oral bacteriotherapy in HIV patients

Objective: To investigate whether a probiotic supplementation to cART patients modifies the cerebrospinal fluid (CSF) proteome and improves neurocognitive impairment. Methods: 26 CSF samples from 13 HIV-positive patients [six patients living with HIV (PLHIV) and seven patients with a history of AIDS (PHAIDS)] were analyzed. All patients underwent to neurocognitive evaluation and blood sampling at baseline and after 6 months of oral bacteriotherapy. Immune phenotyping and activation markers (CD38 and HLA-DR) were evaluated on peripheral blood mononuclear cells (PBMC). Plasma levels of IL-6, sCD14, and MIP-1β were detected, by enzyme-linked immunosorbent assay (ELISA). Functional proteomic analysis of CSF sample was conducted by two-dimensional electrophoresis; a multivariate analysis was performed by principal component analysis (PCA) and data were enriched by STRING software. Results: Oral bacteriotherapy leads to an improvement on several cognitive test and neurocognitive performance in both groups of HIV-positive subjects. A reduction in the percentage of CD4+CD38+HLA–DR+ T cells was also observed at peripheral level after the probiotic intake (p = 0.008). In addition, the probiotic supplementation to cART significantly modifies protein species composition and abundance at the CSF level, especially those related to inflammation (β2-microglobulin p = 0.03; haptoglobin p = 0.06; albumin p = 0.003; hemoglobin p = 0.003; immunoglobulin heavy chains constant region p = 0.02, transthyretin p = 0.02) in PLHIV and PHAIDS. Conclusions: Our results suggest that oral bacteriotherapy as a supplement to cART could exert a role in the amelioration of inflammation state at peripheral and CNS level.     

Peripheral biomarkers do not correlate with cognitive impairment in highly active antiretroviral therapy—treated subjects with human immunodeficiency virus type 1 infection

Neuropsychological (NP) impairments in human immunodeficiency virus (HIV)-infected individuals remain high despite the introduction of highly active antiretroviral therapy (HAART). We sought to determine whether or not a monocyte gene expression profile along with other peripheral factors would correlate with neuropsychological impairment among HIV-infected individuals. Forty-four HIV-1-seropositive subjects (HIV+) on HAART and 11 HIV-1-seronegative controls (HIV−) had NP testing and blood drawn for monocyte gene expression analysis. All HIV+ subjects were assessed for CD4 counts, apolipoprotein E (ApoE) genotype, viral load, and plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14). NP scores were normalized to age, gender, and education. Twenty-five percent of HIV+ individuals showed abnormal NP testing results (>1.5 SD below normal in two domains). HIV+ individuals had deficits in attention/working memory, verbal learning, and information processing speed compared to HIV− controls. There was no correlation between overall NP impairment and plasma viral load, level of education, age, ethnic diversity, sCD14, plasma LPS, CD4 cell count, ApoE genotype, or years of infection. However, greater years of infection had worse visual learning performance. sCD14 and CD4 nadir positively correlated with information processing speed and fine motor skills, respectively. LPS correlated with viral load but not cognitive impairment. Monocyte gene expression confirmed a chronic inflammatory profile that correlated with viral load but not cognition. No blood index or profile was associated with overall NP impairment.     

Cortical Brain Age from Pre-treatment to Post-chemotherapy in Patients with Breast Cancer

Chemotherapy-related cognitive impairment and associated brain changes may reflect accelerated brain aging; however, empirical evidence for this theory is limited. The purpose of this study was to measure brain aging in newly diagnosed patients with breast cancer treated with chemotherapy (n = 43) and compare its longitudinal change to that of controls (n = 50). Brain age indices, derived from cortical measures, were compared between women with breast cancer and matched healthy controls across 3 timepoints (time 1: pre-surgery, time 2: 1 month following chemotherapy completion, and time 3: 1-year post-chemotherapy). The breast cancer group showed a significant decrease in cortical thickness across the 3 timepoints (p < .001) and a trend towards significant increase in predicted brain age especially from pre-treatment (time 1) to post-chemotherapy (time 2) compared to controls (p = 0.08). Greater increase in predicted brain age was related to several clinical factors (HER-2 status, surgery type, and history of neoadjuvant chemotherapy) and greater decrease in cortical thickness was associated with greater decrease in performance on a verbal learning task from time 1 to time 3 (r = − 0.48, p < .01). This study demonstrated evidence of increased cortical brain aging in middle-aged patients with breast cancer following chemotherapy treatment that was associated with decreased verbal memory performance.     

Can the Harter Self-Perception Profile for Adolescents (SPPA) be used as an indicator of psychosocial outcome in adolescents with chronic physical disorders?

To explore the Harter Self-Perception Profile for Adolescents (SPPA) as an indicator of psychosocial outcome in adolescents with chronic physical disorders, we administered the questionnaire along with other well-established measures of psychosocial outcome (the semistructured Child Assessment Schedule (CAS) interview and the Youth Self Report (YSR) and Child Behavior Checklist (CBCL) questionnaires) to one group of diseased adolescents with good psychosocial adjustment (juvenile chronic arthritis, JCA) and one with a high level of psychosocial maladjustment (anorectal anomalies, ARA). The adolescents with ARA had significantly lower scores of global self-worth, school competence, and social acceptance as compared to the adolescents with JCA. However, global self-worth in neither group was impaired as compared with that of the general Norwegian adolescent population. Perceived physical appearance was the single self-concept domain accounting for the variance in global self-worth (R² = 0.71, p < 0.001). Among the other measures of psychosocial outcome, global self-worth was most strongly related to mood according to the CAS interview (r = −0.53, p < 0.001) and to the YSR internalizing score (r = −0.53, p < 0.001). Our findings indicate that the SPPA has limited ability to identify chronically diseased adolescents with adverse psychosocial outcome. Accepted: 28 August 1998     

The nature and consequences of cognitive deficits among tobacco smokers with HIV: a comparison to tobacco smokers without HIV

HIV-infected smokers lose more years of life to tobacco-related disease than HIV. Since neurocognitive deficits are common among those with HIV and are associated with smoking persistence, these deficits may be a unique barrier to smoking cessation among HIV-infected smokers. Documenting unique differences in and correlates of cognition among HIV-infected smokers is a critical step towards developing a population-specific tobacco cessation treatment. We compared neurocognitive function between HIV-infected (n = 103) and HIV-uninfected smokers (n = 70), accounting for demographic and smoking-related variables. We also evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load, depression ratings, quality of life [QoL]) and HAART adherence were associated with cognition. Participants completed neurocognitive tasks (N-back and Continuous Performance Task [CPT]) measuring working memory, attention, and processing speed, and intra-individual variability. Stepwise regression models were conducted and validated with resampling techniques. HIV-infected smokers performed worse than HIV-uninfected smokers on working memory, processing speed, and intra-individual variability (all p < 0.01). ROC analysis for the model including cognitive measures demonstrated 85% area under the curve, which indicates “good prediction” for distinguishing between HIV-infected and HIV-uninfected smokers. This was a significant improvement over the model including demographic and smoking-related variables only (p = 0.0003). Among HIV-infected smokers, neurocognitive performance was negatively associated with QoL and depression ratings. Smoking cessation interventions for HIV-infected smokers should consider cognitive neurorehabilitation as a potential strategy to decrease the likelihood of nicotine relapse and decrease tobacco-related morbidity in this population.     

Functional connectivity measured with magnetoencephalography identifies persons with HIV disease

There is need for a valid and reliable biomarker for HIV Associated Neurocognitive Disorder (HAND). The purpose of the present study was to provide preliminary evidence of the potential utility of neuronal functional connectivity measures obtained using magnetoencephalography (MEG) to identify HIV-associated changes in brain function. Resting state, eyes closed, MEG data from 10 HIV-infected individuals and 8 seronegative controls were analyzed using mutual information (MI) between all pairs of MEG sensors to determine whether there were functional brain networks that distinguished between subject groups based on cognition (global and learning) or on serostatus. Three networks were identified across all subjects, but after permutation testing (at α < .005) only the one related to HIV serostatus was significant. The network included MEG sensors (planar gradiometers) above the right anterior region connecting to sensors above the left posterior region. A mean MI value was calculated across all connections from the anterior to the posterior groupings; that score distinguished between the serostatus groups with only one error (sensitivity = 1.00, specificity = .88 (X ²  = 15.4, df = 1, p < .01, Relative Risk = .11). There were no significant associations between the MI value and the neuropsychological Global Impairment Rating, substance abuse, mood disorder, age, education, CD4+ cell counts or HIV viral load. We conclude that using a measure of functional connectivity, it may be possible to distinguish between HIV-infected and uninfected individuals, suggesting that MEG may have the potential to serve as a sensitive, non-invasive biomarker for HAND.     

Decreased β-Cell Function is Associated with Cardiovascular Autonomic Neuropathy in Chinese Patients Newly Diagnosed with Type 2 Diabetes

The influence of β-cell function on cardiovascular autonomic neuropathy (CAN), an important diabetes-related complication, is still unclear. In this study, we aimed to investigate the association between residual β-cell function and CAN in patients newly diagnosed with type 2 diabetes. We enrolled 90 newly-diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as controls. The patients were divided into a CAN+ group (diabetic patients with CAN, n = 20) and a CAN− group (diabetic patients without CAN, n = 70) according to the standard Ewing battery of tests. Fasting and postprandial plasma glucose, insulin, and C-peptide were measured. Homeostasis model assessment-beta cells (HOMA-B) and HOMA-insulin resistance (IR) were calculated. The prevalence of CAN in this population was 22.2%. Compared with the CAN− group, the CAN+ group had significantly lower fasting plasma insulin (6.60 ± 4.39 vs 10.45 ± 7.82 μ/L, P = 0.029), fasting C-peptide (0.51 ± 0.20 vs 0.82 ± 0.51 nmol/L, P = 0.004), and HOMA-B (21.44 ± 17.06 vs 44.17 ± 38.49, P = 0.002). Fasting C-peptide was correlated with the Valsalva ratio (r = 0.24, P = 0.043) and the 30:15 test (r = 0.26, P = 0.023). Further analysis showed that fasting C-peptide (OR: 0.041, 95% CI 0.003–0.501, P = 0.012) and HOMA-B (OR: 0.965, 95% CI 0.934–0.996, P = 0.028) were independently associated with cardiovascular autonomic nerve function in this population. The patients with fasting C-peptide values < 0.67 nmol/L were more likely to have CAN than those with C-peptide levels ≥0.67 nmol/L (OR: 6.00, 95% CI 1.815–19.830, P = 0.003). A high prevalence of CAN was found in patients with newly-diagnosed type 2 diabetes. Decreased β-cell function was closely associated with CAN in this population.     

Neurologic manifestations of human immunodeficiency virus-2: dementia,myelopathy, and neuropathy in West Africa

While well documented in human immunodeficiency virus (HIV)-1, neurologic sequelae have not been systematically evaluated in HIV-2. After excluding for confounding comorbidities, 67 individuals from a rural cohort in Guinea-Bissau (22 HIV-2 participants, 45 seronegative controls) were evaluated. HIV + individuals were divided into CD4 < 350 and CD4 ≥ 350 for analysis. HIV-associated neurocognitive disorders (HAND), assessed by the International HIV Dementia Scale (IHDS), distal sensory polyneuropathy (DSPN), and myelopathy were the main outcome variables. In univariate analysis, there was no difference in IHDS scores among groups. When analyzed by primary education attainment, IHDS scores were nonsignificantly higher (p = 0.06) with more education. There was no significant difference in DSPN prevalence among groups; overall, 45% of participants had DSPN. There were no cases of myelopathy. In multivariate linear regression, higher IHDS scores were significantly correlated with older age (coefficient = −0.11, p < 0.001). Logistic regression analysis showed that older age (odds ratio (OR) 95% CI 1.04–1.20), lower CD4 count (OR 95% CI 0.996–0.999), and higher BMI (OR 95% CI 1.02–1.43) significantly predicted the presence of DSPN. While a significant increase in cognitive impairment was not observed in HIV-2-infected individuals, the study suggests the IHDS may be a less effective screening tool for HAND in settings of lower educational attainment as encountered in rural Guinea-Bissau. Similar to HIV-1, DSPN seems to occur with lower CD4 counts in HIV-2. Further study of the viral–host interactions in HIV-2 and its consequent neurological diseases may provide an avenue for understanding the epidemic problems of HIV-1.     

Psychometric Evaluation of the Life Orientation Test—Revised in Treated Opiate Dependent Individuals

We examined internal consistency and test-retest reliability of a measure of dispositional optimism, the Life Orientation Test — Revised, in 121 opiate-dependent patients seeking methadone treatment. Internal consistency was adequate at baseline (α = .69) and follow-up (α = .72). Low socioeconomic status and being on disability were significantly associated with reduced internal consistency; ethnic and educational differences approached significance. Test-retest reliability was good (ICC = .72), varying across gender, race, ethnicity, education, employment and income (ICC Range = .24 –.85). Criterion validity was strong; the LOT-R was significantly negatively correlated with hopelessness (r = -.65, p < .001) and depression (r = -.60, p < .001). Findings support the use of this measure of optimism and pessimism to assess positive cognitive and emotional attributes and improve treatment strategies for opiate-dependent individuals. Future research should address the measurement and significance of optimism in minority, low socioeconomic status and poorly-educated individuals.     

A fMRI Study of Verbal Working Memory, Cardiac Output, and Ejection Fraction in Elderly Patients with Cardiovascular Disease

Cardiovascular disease (CVD) is associated with cognitive deficits even in the absence of stroke. We examined the relationship between cardiac performance, as measured by cardiac output (CO) and ejection fraction (EF), and brain activity during a verbal working memory (VWM) task in elderly CVD patients who tend to be at increased risk for vascular cognitive impairments. Seventeen patients were recruited from a cohort participating in an ongoing prospective study examining the effects of CVD on cognitive function in the elderly. Participants were diagnosed with CVD (age 68 ± 8) and completed a 2-back VWM task in a 1.5T fMRI paradigm. CO and EF were calculated from echocardiogram measures. Task-related activation was averaged in a priori regions of interest. The relationship between CO, EF, and 2-back-related activity was modeled using partial correlations (two-tailed p < .05) controlling for age and 2-back accuracy. All participants were globally cognitively intact as indicated by Mini-Mental Status Exam and Dementia Rating Scale scores. Mean accuracy on the 2-back was 78 ± 9% while reaction time averaged 1,027 ± 192 ms. Mean CO and EF values showed a large range (CO: 3.55 to 6.31; EF: 0.36 to 0.76) but average values were within the normal range. After controlling for age and 2-back accuracy, lower EF was related to decrease in left insula activity (r = 0.61, p = 0.03). There were trends for EF to be related to accuracy (r = 0.47, p = 0.09) and reaction time (r = −0.48, p = 0.09). CO was also related to insula activity (r = 0.60, p = 0.04) and activity in the supplementary motor area activity (r = 0.66, p = 0.01). Cardiac performance was related to decreased efficiency in task related brain areas and tended to be related to performance on a VWM task in elderly patients with CVD. Results have implications for a line of investigation indicating that cardiac and systemic vascular indices could be used as proxy measures to examine mechanisms of cerebrovascular dysfunction in the elderly.     

Platelet decline as a predictor of brain injury in HIV infection

An association between platelet decline and increased risk of progression to dementia has been observed in an advanced HIV infection cohort study. This investigation evaluated the prognostic significance of platelet decline for dementia, for psychomotor slowing, and for brain injury, as quantified in vivo, in a much larger population of HIV+ men. Platelet counts and neurocognitive data were available from biannual visits of 2,125 HIV+ men participating in the prospective, Multicenter AIDS Cohort Study from 1984 to 2009. Brain volumetric data were also available from an imaging substudy of 83 seropositive participants aged 50 and older. The association of platelet counts with neurocognitive outcome was assessed using Cox proportional hazard models where change in platelet count from baseline was a time-updated variable. Marked platelet decline was associated with increased risk of dementia in univariate analysis (hazard ratio [HR] = 2.5, 95% confidence interval [CI] = 1.8–3.5), but not after adjustment for CD4 cell count, HIV viral load, age, study site, hemoglobin, race, education, smoking, and alcohol use (HR = 1.4, 95% CI = 0.78–2.5). Platelet decline did not predict psychomotor slowing in either univariate (HR = 0.79, 95% CI = 0.58–1.08) or multivariate (HR = 1.10, 95% CI = 0.73–1.67) analysis. Analysis of brain volumetric data, however, indicated a relationship between platelet decline and reduced gray matter volume fraction in univariate (p = 0.06) and multivariate (p < 0.05) analyses. Platelet decline was not an independent predictor of dementia or psychomotor slowing, after adjusting for stage of disease. Findings from a structural brain imaging substudy of older participants, however, support a possible relationship between platelet decline and reduced gray matter.     

Lipopolysaccharide,Immune Biomarkers and Cerebral Amyloid-Beta Deposition in Older Adults With Mild Cognitive Impairment & Major Depressive Disorder

ObjectiveInflammatory activation and increased immune response to lipopolysaccharide occur in both depression and cognitive decline and may link these two conditions. We investigated whether lipopolysaccharide (LPS), LPS binding protein (LBP) and peripheral biomarkers of immune response were associated with increased cerebral deposition of amyloid-beta (Abeta) in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD).DesignCross-sectional analysis.SettingFive academic health centers in Toronto.ParticipantsOlder adults with MCI with/without rMDD.MeasurementsWe investigated the associations among serum LPS, LBP, biomarkers of inflammatory activation – Interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and cerebral Abeta deposition quantified by positron emission tomography.ResultsAmong 133 study participants (82 with MCI and 51 with MCI+rMDD) there was no association between LPS (beta – 0.17, p = 0.8) or LBP (beta - 0.11, p = 0.12) and global deposition of Abeta following adjustment for age, gender, and APOE genotype in multivariable regression analyses. LBP was positively correlated with CRP (r = 0.5, p <0.001) and IL-6 (r = 0.2, p = 0.02) but no inflammatory biomarker was associated with Abeta deposition; rMDD was not associated with deposition of Abeta (beta -0.09, p = 0.22).ConclusionIn this cross-sectional analysis, we did not find an association among LPS/LBP, immune biomarkers or rMDD and global deposition of Abeta. Future analyses should assess the longitudinal relationships between peripheral and central biomarkers of immune activation, depression and cerebral Abeta deposition.     

Association of long-term patterns of depressive symptoms and attention/executive function among older men with and without human immunodeficiency virus

Older HIV-infected men are at higher risk for both depression and cognitive impairments, compared to HIV-uninfected men. We evaluated the association between longitudinal patterns of depressive symptoms and attention/executive function in HIV-infected and HIV-uninfected men aged 50+ years to understand whether HIV infection influenced the long-term effect of depression on attention/executive function. Responses to the Center for Epidemiologic Studies—Depression scale and attention/executive function tests (Trail Making Test Part B and Symbol Digit Modalities Test) were collected semiannually from May 1986 to April 2015 in 1611 men. Group-based trajectory models, stratified by HIV status, were used to identify latent patterns of depressive symptoms and attention/executive function across 12 years of follow-up. We identified three depression patterns for HIV-infected and HIV-uninfected men (rare/never 50.0 vs. 60.6%, periodically depressed 29.6 vs. 24.5%, chronic high 20.5 vs.15.0%, respectively) and three patterns of attention/executive function for HIV-infected and HIV-uninfected men (worst-performing 47.4 vs. 45.1%; average 41.9 vs. 47.0%; best-performing 10.7 vs. 8.0%, respectively). Multivariable logistic regression models were used to assess associations between depression patterns and worst-performing attention/executive function. Among HIV-uninfected men, those in the periodically depressed and chronic high depressed groups had higher odds of membership in the worst-performing attention/executive function group (adjusted odds ratio [AOR] = 1.45, 95% CI 1.04, 2.03; AOR = 2.25, 95% CI 1.49, 3.39, respectively). Among HIV-infected men, patterns of depression symptoms were not associated with patterns of attention/executive function. Results suggest that HIV-uninfected, but not HIV-infected, men with chronic high depression are more likely to experience a long-term pattern of attention/executive dysfunction.     

Barriers to Mental Health Help Seeking at School for Asian– and Latinx–American Adolescents

Adolescents are most likely to receive mental health services in schools compared to other settings; however, few studies have examined barriers to mental health help seeking at school for ethnic minority adolescents. The current mixed-methods study utilized surveys and semi-structured interviews to explore the mental health literacy (MHL), stigma toward mental illness, and perceived barriers toward help seeking at middle or high schools among 55 adolescents (81.8% female; 50.0% Asian–American, 44.6% Latinx–American, 5.4% Asian/Latinx bi-racial; M age = 17.13 years, SD = 2.33). Participants’ MHL was assessed using case vignettes that depicted adolescents with symptoms of depression or bulimia. Overall, 83.9% of participants correctly recognized depression and 57.1% correctly recognized bulimia from the vignettes. Stigma correlated with perceived helpfulness of the formal service providers (r = − .37, p < .01). Qualitative analysis of participant interviews revealed important knowledge, attitudinal, and practical barriers that inhibit Asian– and Latinx–American adolescents from seeking help for mental health problems at school. The current work has implications to assist school personnel and mental health providers in understanding and reducing barriers to help seeking for Asian– and Latinx–American adolescents.     

Clinical,laboratory, and neuroimaging characteristics of fatigue in HIV-infected individuals

Fatigue is among the most common symptoms reported by HIV-infected individuals. Previous reports suggest that the prevalence of fatigue varies by disease status with rates close to 80% in patients with AIDS. However, most studies have not been conducted in the setting of a controlled trial and have not assessed the association of fatigue with cellular markers of brain activity. Data for this study were derived from baseline and longitudinal evaluations in ACTG A5090, a randomized, double-blind, placebo-controlled trial of the Selegiline Transdermal System for the treatment of HIV-associated cognitive impairment. Fatigue was assessed using the Fatigue Severity Scale with scores of >4 considered “fatigued”. Participants in a substudy underwent brain magnetic resonance spectroscopy (MRS) imaging, an in vivo method for assessing brain metabolites associated with neuronal and glia activity. Differences between fatigued and non-fatigued participants were evaluated with respect to demographics and clinical characteristics, plasma and CSF HIV-1 RNA concentration, CD4 counts, and brain metabolites. One hundred and twenty-eight participants were enrolled (88% male, median age = 45 years) and 82 participants (64%, 95% confidence interval 55%, 72%) were fatigued at baseline. MRS was conducted in 62 of the 128 participants. Fatigued participants were significantly younger (p = 0.011), had lower Karnofsky scores (p = 0.032), and had higher levels of depressive symptoms on the Center for Epidemiologic Studies Depression (CES-D) scale (p < 0.001) than non-fatigued participants. Statistically significant differences between fatigued and non-fatigued groups were not detected for plasma and CSF HIV-1RNA concentration, CD4 counts, or on neuropsychological tests. MRS revealed significantly lower levels of the cellular energy marker total creatine (p = 0.002) in the basal ganglia of fatigued participants. Statistically significant differences in other brain metabolites were not detected. Longitudinal data showed that fatigue persisted and worse fatigue at baseline was predictor of future fatigue. Among the cognitive tests, baseline Stroop score was associated with future fatigue. Fatigue was present in 64% of A5090 study participants and persisted during the 24 weeks of follow-up. Fatigue was associated with worse functional performance and depressive mood. Lower cellular energy levels in the basal ganglia, as measured by MRS total creatine concentration, suggest energy dysmetabolism in this brain region. This observation, taken together with the association between fatigue and neuropsychological tests of frontal lobe performance is consistent with the hypothesis of a striatal–cortical circuitry involvement in the symptoms of fatigue.     

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.     

Soluble CD30 levels in plasma and cerebrospinal fluid in multiple sclerosis, HIV infection and other nervous system diseases

The CD30 molecule, a member of tumor necrosis factor superfamily, has been suggested to be preferentially expressed and released in soluble form by activated T cells that produce T helper 2 type (Th2) cytokines. To evaluate whether determination of soluble CD30 (sCD30) levels could have a diagnostic value in diseases associated with Th1 and Th2 cytokine involvement, we investigated sCD30 in plasma and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS), HIV infection and other nervous system diseases. There was no statistically significant difference for plasma sCD30 levels in these clinical groups. However, patients with HIV infection had higher levels of sCD30 in CSF than MS patients. The mean sCD30 values were 3 to 6 folds higher in plasma than in CSF in all patient groups. No relationships were found between sCD30 levels and different clinical variables of MS and HIV infection, except that higher plasma sCD30 levels in HIV-infected patients were found in those with higher CD4⁺ T cell counts (> 200 ± 10⁶) compared to the group with lower cell counts. The findings indicate that determinations of plasma and CSF sCD30 levels in MS and HIV infection have limited or no value as diagnostic or prognostic indicator.     

Machine learning models reveal neurocognitive impairment type and prevalence are associated with distinct variables in HIV/AIDS

Neurocognitive impairment (NCI) among HIV-infected patients is heterogeneous in its reported presentations and frequencies. To determine the prevalence of NCI and its associated subtypes as well as predictive variables, we investigated patients with HIV/AIDS receiving universal health care. Recruited adult HIV-infected subjects underwent a neuropsychological (NP) test battery with established normative (sex-, age-, and education-matched) values together with assessment of their demographic and clinical variables. Three patient groups were identified including neurocognitively normal (NN, n = 246), HIV-associated neurocognitive disorders (HAND, n = 78), and neurocognitively impaired-other disorders (NCI-OD, n = 46). Univariate, multiple logistic regression and machine learning analyses were applied. Univariate analyses showed variables differed significantly between groups including birth continent, quality of life, substance use, and PHQ-9. Multiple logistic regression models revealed groups again differed significantly for substance use, PHQ-9 score, VACS index, and head injury. Random forest (RF) models disclosed that classification algorithms distinguished HAND from NN and NCI-OD from NN with area under the curve (AUC) values of 0.87 and 0.77, respectively. Relative importance plots derived from the RF model exhibited distinct variable rankings that were predictive of NCI status for both NN versus HAND and NN versus NCI-OD comparisons. Thus, NCI was frequently detected (33.5%) although HAND prevalence (21%) was lower than in several earlier reports underscoring the potential contribution of other factors to NCI. Machine learning models uncovered variables related to individual NCI types that were not identified by univariate or multiple logistic regression analyses, highlighting the value of other approaches to understanding NCI in HIV/AIDS.