White Matter Deficits Assessed by Diffusion Tensor Imaging and Cognitive Dysfunction in Psychostimulant Users With Comorbid Human Immunodeficiency Virus Infection

Background Psychostimulant drug use is commonly associated with drug-related infection, including the human immunodeficiency virus (HIV). Both psychostimulant use and HIV infection are known to damage brain white matter and impair cognition. To date, no study has examined white matter integrity using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in chronic psychostimulant users with comorbid HIV infection, and determined the relationship of white matter integrity to cognitive function. Methods Twenty-one subjects (mean age 37.5 ± 9.0 years) with a history of heavy psychostimulant use and HIV infection (8.7 ± 4.3 years) and 22 matched controls were scanned on a 3T MRI. Fractional anisotropy (FA) values were calculated with DTI software. Four regions of interest were manually segmented, including the genu of the corpus callosum, left and right anterior limbs of the internal capsule, and the anterior commissure. Subjects also completed a neurocognitive battery and questionnaires about physical and mental health. Results The psychostimulant using, HIV positive group displayed decreased white matter integrity, with significantly lower FA values for all white matter tracts (p < 0.05). This group also exhibited decreased cognitive performance on tasks that assessed cognitive set-shifting, fine motor speed and verbal memory. FA values for the white matter tracts correlated with cognitive performance on many of the neurocognitive tests. Conclusions White matter integrity was thus impaired in subjects with psychostimulant use and comorbid HIV infection, which predicted worsened cognitive performance on a range of tests. Further study on this medical comorbidity is required

Component Processes of Decision Making in a Community Sample of Precariously Housed Persons: Associations With Learning and Memory, and Health-Risk Behaviors

The Iowa Gambling Task (IGT) is a widely used measure of decision making, but its value in signifying behaviors associated with adverse, “real-world” consequences has not been consistently demonstrated in persons who are precariously housed or homeless. Studies evaluating the ecological validity of the IGT have primarily relied on traditional IGT scores. However, computational modeling derives underlying component processes of the IGT, which capture specific facets of decision making that may be more closely related to engagement in behaviors associated with negative consequences. This study employed the Prospect Valence Learning (PVL) model to decompose IGT performance into component processes in 294 precariously housed community residents with substance use disorders. Results revealed a predominant focus on gains and a lack of sensitivity to losses in these vulnerable community residents. Hypothesized associations were not detected between component processes and self-reported health-risk behaviors. These findings provide insight into the processes underlying decision making in a vulnerable substance-using population and highlight the challenge of linking specific decision making processes to “real-world” behaviors

The impact of viral infections on neurocognitive functioning in the context of multiple risk factors: Associations with health care utilization

Marginally housed persons experience several risk factors for neurocognitive impairment, including viral infections, psychiatric illness, and substance use. Although interventions exist, marginalized persons often obtain inadequate health services, based upon personal and structural barriers. In study one, we employed structural equation modeling to assess determinants of neurocognition (i.e., viral infections, psychiatric symptoms), predicting that any impairment would impede healthcare access. Our findings revealed that greater exposure to viral infections and more severe psychiatric symptoms were similarly associated with poorer neurocognition. Additionally, more frequent opioid use/less frequent alcohol and marijuana use was associated with better neurocognition. Only viral infections directly predicted healthcare use, an association that was positive despite the negative impact viral infections held with neurocognition. In study two, we assessed whether spontaneous clearance of Hepatitis C (HCV) is associated with reversal of neurocognitive impairments by comparing three groups: cleared-HCV, active-HCV, and no exposure to HCV. Our findings did not confirm improved neurocognition with HCV clearance, nor did we find any differences between groups exposed to HCV versus those never exposed to the virus after controlling for the effects of Hepatitis B (HBV). Nevertheless, our findings revealed that HCV conveys adverse health in marginalized persons (i.e., HCV exposure is associated with increased rates of HIV, liver dysfunction, etc.). Overall, these findings confirm the detrimental impact of viral infections on neurocognition in marginalized persons. Moreover, although neurocognition did not emerge as a personal barrier to accessing care in marginalized settings, structural level barriers may be operating. Specifically, our results point to a system where health care is selectively utilized and may not be targeted towards all persons, such as those experiencing elevated psychiatric symptoms

Select Neurocognitive Impairment in HIV-Infected Women: Associations with HIV Viral Load, Hepatitis C Virus, and Depression, but Not Leukocyte Telomere Length

Background Through implementation of combination antiretroviral therapy (cART) remarkable gains have been achieved in the management of HIV infection; nonetheless, the neurocognitive consequences of infection remain a pivotal concern in the cART era. Research has often employed norm-referenced neuropsychological scores, derived from healthy populations (excluding many seronegative individuals at high risk for HIV infection), to characterize impairments in predominately male HIV-infected populations. Methods Using matched-group methodology, we assessed 81 HIV-seropositive (HIV+) women with established neuropsychological measures validated for detection of HIV-related impairments, as well as additional detailed tests of executive function and decision-making from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results On validated tests, the HIV+ women exhibited impairments that were limited to significantly slower information processing speed when compared with 45 HIV-seronegative (HIV−) women with very similar demographic backgrounds and illness comorbidities. Additionally, select executive impairments in shifting attention (i.e., reversal learning) and in decision-making quality were revealed in HIV+ participants. Modifiers of neurocognition in HIV-infected women included detectable HIV plasma viral load, active hepatitis C virus co-infection, and self-reported depression symptoms. In contrast, leukocyte telomere length (LTL), a marker of cellular aging, did not significantly differ between HIV+ and HIV− women, nor was LTL associated with overall neurocognition in the HIV+ group. Conclusions The findings suggest that well-managed HIV infection may entail a more circumscribed neurocognitive deficit pattern than that reported in many norm-referenced studies, and that common comorbidities make a secondary contribution to HIV-related neurocognitive impairments

The Positive and Negative Syndrome Scale (PANSS): A Three-Factor Model of Psychopathology in Marginally Housed Persons with Substance Dependence and Psychiatric Illness.

Rates of psychopathology are elevated in marginalized and unstably housed persons, underscoring the need for applicable clinical measures for these populations. The Positive and Negative Syndrome Scale (PANSS) is a clinical instrument principally developed for use in schizophrenia to identify the presence and severity of psychopathology symptoms. The current study investigates whether a reliable and valid PANSS factor structure emerges in a marginally housed, heterogeneous sample recruited from the Downtown Eastside of Vancouver where substance use disorders and psychiatric illness are pervasive. Participants (n = 270) underwent structured clinical assessments including the PANSS and then were randomly assigned to either exploratory (EFA) or confirmatory factor analytic (CFA) subsamples. EFA pointed to a novel three factor PANSS. This solution was supported by CFA. All retained items (28 out of 30) load significantly upon hypothesized factors and model goodness of fit analyses are in the acceptable to good range. Each of the three first-order factor constructs, labeled Psychosis/Disorganized, Negative Symptoms/Hostility, and Insight/Awareness, contributed significantly to measurement of a higher-order psychopathology construct. Further, the latent structure of this 3-factor solution appears temporally consistent over one-year. This PANSS factor structure appears valid and reliable for use in persons with multimorbidity, including substance use disorders. The structure is somewhat distinct from existing solutions likely due to the unique characteristics of this marginally housed sample

Demographic and clinical characteristics of HIV+ and HIV− participants.

<p><i>Note.</i> Values represent Mean (standard deviation) unless otherwise indicated; WTAR = Wechsler Test of Adult Reading (full-scale IQ); Asian includes South Asian; CES-D = Center for Epidemiologic Studies Depression Scale (unadjusted means are displayed, but square root transformed scores were used for statistical analysis); HCV = Hepatitis C Virus; % Heavy Use = Daily or weekly use of substance over lifetime; % Recent use = self-reported substance use within 24 hours of neurocognitive testing; Undetectable HIV RNA = viral load ≤200 copies/mL; Groups compared using:</p>a<p>independent <i>t</i>-tests,</p>b<p>χ2 Pearson chi-square;</p>c<p>Fisher's exact test (2-sided);</p>d<p>ANCOVA; n/a = not applicable;</p>†<p><i>p</i><.10;</p><p>*<i>p</i><.05.</p

Correlations between neurocognitive performance and disease- and treatment-related variables, and comorbid conditions in the HIV+ group.

<p><i>Note.</i> Values represent partial <i>r</i>'s controlling for age and education (unless indicated otherwise); HVLT = Hopkin's Verbal Learning Test- Revised; PAL = Paired Associates Learning; SS = Symbol Search; RVP = Rapid Visual Information Processing; LNS = Letter-Number Sequencing; SWM = Spatial Working Memory; SST = Stop Signal Task; IED = Intra-Extra Dimensional Set Shift; CGT = Cambridge Gambling Task; SOC = Stockings of Cambridge; CCI = Composite Cognitive Index; err = errors; Detectable viral load = >200 copies/mL; ART = Antiretroviral Therapy; HCV = Hepatitis C virus;</p>a<p>Square root transformed data;</p>b<p>Cubed transformation;</p>c<p>Spearman's <i>rho</i>;</p>†<p><i>p</i><.10;</p><p>*<i>p</i><.05;</p><p>**<i>p</i><.01.</p

Executive functioning test descriptions.

<p>Executive functioning test descriptions.</p

Cognitive profiles and associated structural brain networks in a multimorbid sample of marginalized adults.

IntroductionCognition is impaired in homeless and vulnerably housed persons. Within this heterogeneous and multimorbid group, distinct profiles of cognitive dysfunction are evident. However, little is known about the underlying neurobiological substrates. Imaging structural covariance networks provides a novel investigative strategy to characterizing relationships between brain structure and function within these different cognitive subgroups.MethodParticipants were 208 homeless and vulnerably housed persons. Cluster analysis was used to group individuals on the basis of similarities in cognitive functioning in the areas of attention, memory, and executive functioning. The principles of graph theory were applied to construct two brain networks for each cognitive group, using measures of cortical thickness and gyrification. Global and regional network properties were compared across networks for each of the three cognitive clusters.ResultsThree cognitive groups were defined by: higher cognitive functioning across domains (Cluster 1); lower cognitive functioning with a decision-making strength (Cluster 3); and an intermediate group with a relative executive functioning weakness (Cluster 2). Between-group differences were observed for cortical thickness, but not gyrification networks. The lower functioning cognitive group exhibited higher segregation and reduced integration, higher centrality in select nodes, and less spatially compact modules compared with the two other groups.ConclusionsThe cortical thickness network differences of Cluster 3 suggest that major disruptions in structural connectivity underlie cognitive dysfunction in a subgroup of people who have a high multimorbid illness burden and who are vulnerably housed or homeless. The origins, and possible plasticity of these structure-function relationships identified with network analysis warrant further study

Clinical and functional associations of three factors.

<p>Clinical and functional associations of three factors.</p