Objective To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of highly active antiretroviral therapy (HAART). Design This study is an observational cohort study. Methods MRS was performed in 268 patients: HIV-negative controls (N=28), HIV-positive neuroasymptomatic (NA) subjects (N=124), and subjects with AIDS Dementia Complex (ADC; N=50) on stable ART with a mean duration of infection of 12 years and CD4 of 309 cells/mm3. Four metabolites were measured over creatine (Cr): N-acetyl aspartate (NAA), marker of neuronal integrity; Choline (Cho), myoinositol (MI), markers of inflammation, and glutamate and glutamine (Glx) in the basal ganglia (BG), frontal white matter (FWM) and mid-frontal Cortex (MFC). Analyses included ANOVA, ANCOVA, linear and nonparametric regression models. Results Cognitive impairment was found in 48% of HIV infected subjects. Both HIV positive groups showed significant increases in MI/Cr or Cho/Cr in all brain regions when compared to controls; a significant decrease in Glx/Cr in the FWM was observed in the NA group; only ADC subjects showed a significant reduction in NAA/ Cr although a significant trend for decreasing NAA/Cr in the BG was found across the groups. Effects related to aging and duration of infection but not central nervous system penetration effectiveness (CPE) were observed. Conclusions Brain inflammatory changes remain ubiquitous among HIV-infected subjects whereas neuronal injury occurs predominantly in those with cognitive impairment. Together these findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease.
This innovative approach eliminates the traditional instruction set interface and instead exposes the details of a simple replicated architecture directly to the compiler. This allows the compiler to customize the hardware to each application.
Memory and executive functioning are two important components of clinical neuropsychological (NP) practice and research. Multiple demographic factors are known to affect performance differentially on most NP tests, but adequate normative corrections, inclusive of race/ethnicity, are not available for many widely used instruments. This study compared demographic contributions for widely used tests of verbal and visual learning and memory (Brief Visual Memory TestRevised, Hopkins Verbal Memory Test-Revised), and executive functioning (Stroop Color and Word Test, Wisconsin Card Sorting Test-64) in groups of healthy Caucasians (n = 143) and African-Americans (n = 103). Demographic factors of age, education, gender, and race/ethnicity were found to be significant factors on some indices of all four tests. The magnitude of demographic contributions (especially age) was greater for African-Americans than Caucasians on most measures. New, demographically corrected T-score formulas were calculated for each race/ ethnicity. The rates of NP impairment using previously published normative standards significantly overestimated NP impairment in African-Americans. Utilizing the new demographic corrections developed and presented herein, NP impairment rates were comparable between the two race/ethnicities and unrelated to the other demographic characteristics (age, education,
Objective-Differences in antiretroviral (ARV) distribution into the central nervous system (CNS) may impact neurocognitive status. We assessed the relationship between estimates of ARV therapy penetration into the CNS, using a published ranking system, and neurocognitive status in HIV-positive subjects with plasma HIV-1 RNA (vRNA) suppression.Design-Subjects with ≥6 weeks ongoing ARV use and vRNA<50 copies/mL (N=2,636; 83% male, median baseline CD4 T-cells: 244 cells/uL) had ≥1 neuroscreen assessment (Trailmaking A,B, WAIS-R Digit Symbol) at 10,413 neurovisits. Neuroscreen test scores were demographically adjusted and converted to Z-scores (NPZ3: lower scores imply more impairment). CNS penetration-effectiveness (CPE) ranks of 0.0(low), 0.5(medium) or 1.0(high) were assigned to ARVs and summed per regimen, per neurovisit. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Role of author:Marlene Smurzynski: study and conceptual design, assisted with data analysis, interpretation of findings, wrote and edited manuscript, finalized manuscript for publication Kunling Wu: data analysis, created figures and tables, interpretation of findings, reviewed manuscript Scott Letendre: study and conceptual design, interpretation of findings, contributed to manuscript development, edited manuscript Kevin Robertson: study and conceptual design, interpretation of findings, edited manuscript Ronald J. Bosch: assisted with data analysis, interpretation of findings, edited manuscript David B. Clifford: interpretation of findings, edited manuscript Scott Evans: assisted with data analysis, interpretation of findings, reviewed manuscript Ann C. Collier: interpretation of findings, edited manuscript Michael Taylor: completed the normalized neurocognitive test scores (NPZ3 scores), reviewed manuscript Ronald Ellis: study and conceptual design, interpretation of findings, contributed to manuscript development, edited manuscript NIH Public Access Methods-Multivariate linear regression models using generalized estimating equations assessed NPZ3 scores with respect to ARV regimen. Covariates were retained if p≤0.1.Results-A final model demonstrated that better NPZ3 scores were associated with higher CPE among subjects taking >3 ARVs (+0.07 per one unit increase in CPE score; p=0.004) but not among subjects with ≤3 ARVs in the regimen (+0.01; p=0.5). Results were adjusted for demographics, injection drug use, HCV serostatus, CD4 count (current and nadir), baseline vRNA, ARV experience and years since first ARV use.Conclusions-Use of ARVs with better estimated CNS penetration may be associated wi...
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The inter-site and intra-site variability of system performance of MRI scanners (due to site-dependent and time-variant variations) can have significant adverse effects on the integration of multi-center DTI data. Measurement errors in accuracy and precision of each acquisition determine both the inter-site and intra-site variability. In this study, multiple scans of an identical isotropic diffusion phantom and of the brain of a travelling human volunteer were acquired at MRI scanners from the same vendor and with similar configurations at three sites. We assessed the feasibility of multi-center DTI studies by direct quantification of accuracy and precision of each dataset. Accuracy was quantified via comparison to carefully constructed gold standard datasets while precision (the within-scan variability) was estimated by wild bootstrap analysis. The results from both the phantom and human data suggest that the inter-site variation in system performance, although relatively small among scanners of the same vendor, significantly affects DTI measurement accuracy and precision and therefore the effectiveness for the integration of multi-center DTI measurements. Our results also highlight the value of a DTI-specific phantom in identifying and quantifying measurement errors due to site-dependent variations in the system performance, and its usefulness for quality assurance/quality control in multi-center DTI studies. In addition, we observed that the within-scan variability of each data acquisition, as assessed by wild bootstrap analysis, is of the same magnitude as the inter-site and intra-site variability. We propose that by weighing datasets based on their variability, as evaluated by wild bootstrap analysis, one can improve the quality of the dataset. This approach will provide a more effective integration of datasets from multi-center DTI studies.
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