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1.  The aggregate effects of multiple comorbid risk factors on cognition among HIV-infected individuals 
This study developed and then cross-validated a novel weighting algorithm based on multiple comorbid risk factors (stimulant use, vascular disease, hepatitis C, HIV disease severity, cognitive reserve) to predict cognitive functioning among 366 HIV+ adults. The resultant “risk severity score” was used to differentially weight, as a function of age, the impact and magnitude of multiple risk factors on cognition. Among older adults (> 50 years) the risk severity index was differentially predictive of learning/memory and verbal fluency, whereas among younger adults it was linked to working memory and executive function. Cognitive reserve was found to be the most robust predictor of neurocognition.
doi:10.1080/13803395.2013.783000
PMCID: PMC3641576  PMID: 23547924
2.  Functional disability in medication management and driving among individuals with HIV: A 1-year follow-up study 
Approximately 50% of individuals with HIV report cognitive deficits that can affect social or occupational functioning. The present study used a longitudinal design (1 year) to examine the relationship between cognitive factors and incidental functional deficits in medication management and driving ability among a cohort of 101 HIV+ participants. Participants were classified into groups of functionally “stable” and “disabled” for each laboratory-based functional task (i.e., Medication Management Task–Revised, MMT–R, and PC-based driving simulator). We hypothesized that participants who exhibited a functional deficit in either MMT–R or driving at follow-up assessment would demonstrate significantly poorer baseline cognitive performance at study entry than participants who remained functionally stable. As hypothesized, participants who demonstrated significantly lower baseline performance in learning/memory and executive functioning also demonstrated functional disability on the MMT–R at follow-up when compared to functionally stable participants. Poor baseline performance in speed of information processing was associated with a deficit in driving ability at follow-up assessment. Our results suggest that lower baseline cognitive functioning predicts downstream functional disability, and that deficits in learning/memory and information processing speed are particularly predictive of deficits in medication management and driving ability.
doi:10.1080/13803395.2012.747596
PMCID: PMC3622554  PMID: 23237014
HIV; Instrumental activities of daily living; Cognitive function; Medication management; Driving
3.  Emerging Issues in the Neuropsychology of HIV Infection 
Current HIV/AIDS reports  2008;5(4):204-211.
Neurocognitive compromise, a common sequela of HIV infection, ranges in severity from minor motor and information-processing speed decrements to severely incapacitating symptoms that affect functional independence. However, with the emergence of highly active antiretroviral therapy (HAART), neurocognitive phenotypes have become highly heterogeneous and increasingly fail to resemble pre-HAART presentations. This article provides an overview of our current knowledge of HIV-associated neuropsychological abnormalities, with an emphasis on the most recent attempts to classify cognitive impairment within Western and developing societies, the emergence of diverse cognitive presentations in the post-HAART era, factors that moderate the development or impact of HIV-related neurocognitive and functional deficits, and the neurophysiologic consequences of infection.
PMCID: PMC3616484  PMID: 18838060
4.  Medication and finance management among HIV-infected adults: The impact of age and cognition 
This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report.
doi:10.1080/13803395.2010.499357
PMCID: PMC3616485  PMID: 20694873
Neuropsychology; HIV; Aging; Functional abilities; Medication management; Finance management
5.  Depression, Cognition, and Self-Appraisal of Functional Abilities in HIV: An Examination of Subjective Appraisal Versus Objective Performance 
The Clinical neuropsychologist  2011;25(2):224-243.
Depression frequently co-occurs with HIV infection and can result in self-reported overestimates of cognitive deficits. Conversely, genuine cognitive dysfunction can lead to an under-appreciation of cognitive deficits. The degree to which depression and cognition influence self-report of capacity for instrumental activities of daily living (IADLs) requires further investigation. This study examined the effects of depression and cognitive deficits on self-appraisal of functional competence among 107 HIV-infected adults. As hypothesized, higher levels of depression were found among those who over-reported problems in medication management, driving, and cognition when compared to those who under-reported or provided accurate self-assessments. In contrast, genuine cognitive dysfunction was predictive of under-reporting of functional deficits. Together, these results suggest that over-reliance on self-reported functional status poses risk for error when diagnoses require documentation of both cognitive impairment and associated functional disability in everyday life.
doi:10.1080/13854046.2010.539577
PMCID: PMC3616492  PMID: 21331979
Depression; Self-report; Functional ability; Cognition; HIV
6.  Basal ganglia structures differentially contribute to verbal fluency: Evidence from Human Immunodeficiency Virus (HIV)-infected adults 
Neuropsychologia  2011;50(3):390-395.
Background
The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to lexicosemantic verbal fluency performance among older HIV infected adults.
Method
20 older (50+ years) HIV+ adults underwent MRI and were administered measures of semantic and phonemic fluency. BG (caudate, putamen) regions of interest were extracted.
Results
Performance on phonemic word generation significantly predicted caudate volume, whereas performance on phonemic switching predicted putamen volume.
Conclusions
These findings suggest a double dissociation of BG involvement in verbal fluency tasks with the caudate subserving word generation and the putamen associated with switching. As such, verbal fluency tasks appear to be selective to BG function.
doi:10.1016/j.neuropsychologia.2011.12.010
PMCID: PMC3608185  PMID: 22223078
Basal ganglia; Verbal fluency; Magnetic resonance imaging; Human Immunodeficiency Virus; Neuropsychology; Aging
7.  The Role of HIV Infection, Cognition, and Depression in Risky Decision-Making 
The authors examined the impact of HIV, cognitive dysfunction, and depression on decision-making. HIV+ (N=100) and HIV− (N=26) participants were administered a comprehensive neuropsychological battery, a modified version of the Iowa Gambling Task, and a measure of depressive symptoms. HIV+ participants demonstrated more difficulties in learning the gambling task than did HIV− participants. Executive functioning and depression emerged as strong predictors of gambling task performance. Depression partially mediated the relationship between executive functioning and gambling performance. Our findings suggest that HIV infection, executive dysfunction, and depression place individuals at risk for poor decision-making.
doi:10.1176/appi.neuropsych.11110340
PMCID: PMC3608191  PMID: 23037648
8.  Antiretroviral Adherence and the Nature of HIV-Associated Verbal Memory Impairment 
The authors investigated the relationship between antiretroviral adherence and HIV-associated verbal memory impairment. HIV-positive participants demonstrated poorer verbal memory than HIV-negative participants. Both good (≥90%) and poor (<90%) adherers displayed encoding deficits as compared with controls, but only poor adherers exhibited retrieval deficits. Encoding deficits primarily accounted for reduced delayed recall in good adherers, but both encoding and retrieval deficits accounted for reduced delayed recall in poor adherers. The retrieval difference between the adherence groups might be explained by a neuroprotective effect of good antiretroviral adherence or preexisting HIV-related retrieval deficits that result in poorer adherence.
doi:10.1176/appi.neuropsych.23.3.324
PMCID: PMC3603356  PMID: 21948894
9.  Medication adherence in HIV-infected adults: effect of patient age, cognitive status, and substance abuse 
AIDS (London, England)  2004;18(Suppl 1):S19-S25.
Objective:
To examine the predictors of antiretroviral adherence among HIV-infected adults, with a particular focus on advancing age, neuropsychological dysfunction, and substance abuse.
Design:
Prospective observational design.
Methods:
Participants were 148 HIV-infected adults between the ages of 25 and 69 years, all on a self-administered antiretroviral regimen. Medication adherence was tracked over a one-month period using an electronic monitoring device (medication event monitoring system caps). All participants completed a comprehensive battery of neuropsychological tests as well as a structured psychiatric interview.
Results:
The mean adherence rate for the entire cohort was 80.7%, with older patients (⩾ 50 years) demonstrating significantly better medication adherence than younger patients (87.5 versus 78.3%). Logistic regression analyses found that older patients were three times more likely to be classified as good adherers (defined as ⩾ 95% adherent). Neurocognitive impairment conferred a 2.5 times greater risk of poor adherence. Among the older patients, those who were classified as poor adherers performed significantly worse on neuropsychological testing, particularly on measures of executive function and psychomotor speed. Current drug abuse/dependence, but not current alcohol abuse/dependence, was also associated with sub-optimal medication adherence.
Conclusion:
Although older age is associated with higher rates of antiretroviral adherence, older participants who were cognitively impaired showed disproportionate difficulty in adequately adhering to their medication regimen. As such, efforts to detect neuropsychological dysfunction, particularly among older patients, and a thorough assessment of substance abuse, appear to be essential for the effective treatment of HIV-infected adults.
PMCID: PMC2886736  PMID: 15075494
aging; alcohol abuse; drug abuse; electronic monitoring; medication adherence; neuropsychology
10.  Neuropsychological Dysfunction among HIV Infected Drug Abusers 
Human immunodeficiency virus (HIV) has been documented to cause direct and indirect central nervous system dysfunction that can be observed as a progressive decline in neuropsychological functioning in a large proportion of persons with HIV and AIDS. Neuropsychological decline in individuals with HIV is characterized by cognitive and motor slowing, attentional deficits, executive dysfunction and memory impairment (characterized by intact recognition and deficits in learning and delayed recall). Dementia occurs in a relatively small proportion of HIV infected individuals, though milder NP deficits are observed in 30-50% of persons with advanced disease. Recent evidence suggests that drug users, especially stimulant users, are at risk for accelerated progression of their HIV disease, including a greater risk of neuropsychological dysfunction. Methamphetamine may potentiate HIV Tat protein mediated neurotoxicity giving rise to striatal proinflammatory cytokine stimulation and activation of redox-regulated transcription factors. Oxidative stress due to mitochondrial dysfunction is another candidate process underlying the synergistic effects of stimulant use and HIV. Damage to neurotransmitter systems including the dopaminergic, serotonergic and glutamatergic systems which are affected by both stimulant use and HIV is an alternate explanation. Methamphetamine has also been shown to impede the effectiveness of HAART, which could then in turn allow for more rapid HIV disease progression. A greater prevalence of psychiatric disorders, particularly mood, anxiety and substance use disorders are also observed in HIV positive samples relative to the general population. The changing nature of the HIV pandemic is an ongoing challenge to investigators and clinicians working in this field. Emerging issues requiring additional attention are study of the interactive effects of normal aging and HIV on neurocognition as well as study of the effects of co-infection with Hepatitis C.
PMCID: PMC2868271  PMID: 20467580
HIV; AIDS; Neuropsychology; Drug Abuse
11.  Systems analysis of human brain gene expression: mechanisms for HIV-associated neurocognitive impairment and common pathways with Alzheimer’s disease 
Background
Human Immunodeficiency Virus-1 (HIV) infection frequently results in neurocognitive impairment. While the cause remains unclear, recent gene expression studies have identified genes whose transcription is dysregulated in individuals with HIV-association neurocognitive disorder (HAND). However, the methods for interpretation of such data have lagged behind the technical advances allowing the decoding genetic material. Here, we employ systems biology methods novel to the field of NeuroAIDS to further interrogate extant transcriptome data derived from brains of HIV + patients in order to further elucidate the neuropathogenesis of HAND. Additionally, we compare these data to those derived from brains of individuals with Alzheimer’s disease (AD) in order to identify common pathways of neuropathogenesis.
Methods
In Study 1, using data from three brain regions in 6 HIV-seronegative and 15 HIV + cases, we first employed weighted gene co-expression network analysis (WGCNA) to further explore transcriptome networks specific to HAND with HIV-encephalitis (HIVE) and HAND without HIVE. We then used a symptomatic approach, employing standard expression analysis and WGCNA to identify networks associated with neurocognitive impairment (NCI), regardless of HIVE or HAND diagnosis. Finally, we examined the association between the CNS penetration effectiveness (CPE) of antiretroviral regimens and brain transcriptome. In Study 2, we identified common gene networks associated with NCI in both HIV and AD by correlating gene expression with pre-mortem neurocognitive functioning.
Results
Study 1: WGCNA largely corroborated findings from standard differential gene expression analyses, but also identified possible meta-networks composed of multiple gene ontology categories and oligodendrocyte dysfunction. Differential expression analysis identified hub genes highly correlated with NCI, including genes implicated in gliosis, inflammation, and dopaminergic tone. Enrichment analysis identified gene ontology categories that varied across the three brain regions, the most notable being downregulation of genes involved in mitochondrial functioning. Finally, WGCNA identified dysregulated networks associated with NCI, including oligodendrocyte and mitochondrial functioning. Study 2: Common gene networks dysregulated in relation to NCI in AD and HIV included mitochondrial genes, whereas upregulation of various cancer-related genes was found.
Conclusions
While under-powered, this study identified possible biologically-relevant networks correlated with NCI in HIV, and common networks shared with AD, opening new avenues for inquiry in the investigation of HAND neuropathogenesis. These results suggest that further interrogation of existing transcriptome data using systems biology methods can yield important information.
doi:10.1186/1755-8794-6-4
PMCID: PMC3626801  PMID: 23406646
HIV encephalitis; HIV-associated dementia; HIV-associated neurocognitive disorder; Weighted gene coexpression network analysis; WGCNA; CNS penetration effectiveness; National neuroAIDS tissue consortium; Coexpression module
12.  Multi-dimensional MR Spectroscopy: Towards a Better Understanding of Hepatic Encephalopathy 
Metabolic brain disease  2011;26(3):173-184.
Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests. The goals of this study were to quantify cerebral metabolites, separate glutamate (Glu) from glutamine (Gln) in patients with minimal hepatic encephalopathy (MHE) as well as healthy subjects using the prior-knowledge fitting (ProFit) algorithm on data acquired by two-dimensional (2D) localized correlated spectroscopic (L-COSY) on two different MR scanners, and to correlate the metabolite changes with neuropsychological (NP) tests. We studied 14 MHE patients and 18 healthy controls using a GE 1.5T Signa MR scanner. Another group of 16 MHE patients and 18 healthy controls were studied using a Siemens 1.5T Avanto MR scanner. The following parameters were used for L-COSY: TR/TE=2s/30ms, 3×3×3cm3 voxel size, 96 Δt1 increments with 8 averages per Δt1. Using the ProFit algorithm, we were able to differentiate Gln from Glu on the GE 1.5T data in the medial frontal white/gray matter. The ratios of myo-inositol (mI), Glu, total choline, scyllo-inositol (sI), phosphoethanolamine (PE), and total N-acetyl aspartate (NAA) showed statistically significant decline in HE patients compared to healthy controls, while the ratio of Gln was significantly increased. Similar trend was seen in the ProFit quantified Siemens 1.5T data in the frontal and occipito-parietal white/gray regions. Among the NP domain scores, motor function, cognitive speed, executive function and the global scores showed significant differences. Excellent correlations between various NP domains and metabolite ratios were also observed. ProFit based cerebral metabolite quantitation enhances the understanding and basis of the current hypothesis of MHE.
doi:10.1007/s11011-011-9250-1
PMCID: PMC3181227  PMID: 21698453
MRS; COSY; hepatic encephalopathy; glutamine; glutamate; neuropsychological tests
13.  Reaction Time Variability in HIV-Positive Individuals 
Progression of HIV/AIDS is frequently associated with frontal/subcortical dysfunction and mean reaction time (RT) slowing. Beyond group means, within-subject variability of RT has been found to be particularly sensitive to frontal/subcortical dysfunction in other populations. However, the possible relevance of RT variability to HIV/AIDS patients remains unknown. This study evaluated the relationships between RT variability and indicators such as neurocognitive, behavioral, and immunological status. A total of 46 HIV-positive adults on antiretroviral medication regimens were included in this study. Overall performance of this sample was poorer than normative means on measures of RT latency, RT variability, and traditional neurocognitive domains. Results demonstrated that the measures of RT variability were associated with global cognition, medication adherence rates, and peak immunological dysfunction, above and beyond the effects of RT latency. These preliminary findings suggest that measures of RT variability may provide enhanced sensitivity to neurocognitive disease burden in HIV/AIDS relative to more traditional measures of mean RT or cognitive function.
doi:10.1093/arclin/acq064
PMCID: PMC2979347  PMID: 20798183
AIDS; Cognitive ability; Medication adherence; Immunological status; Continuous Performance Test; CPT-II
14.  Reciprocal prediction of medication adherence and neurocognition in HIV/AIDS(e–Pub ahead of print) 
Neurology  2010;74(15):1217-1222.
Background:
Antiretroviral medications have been shown to benefit neurocognition in HIV/AIDS, and neurocognitive deficits are a risk factor for poor adherence to these medications. However, little is known about the predictive pathways linking medication adherence with cognitive ability.
Methods:
In the current 6-month cohort study, antiretroviral medication adherence was tracked prospectively among 91 HIV-positive adults using electronic monitoring. Comprehensive neuropsychological evaluations were performed at baseline and 6 months.
Results:
Multivariate path analyses provided evidence that antiretroviral adherence and cognitive ability are reciprocally related, although the neurocognitive pathways of this relationship appear to vary by predictive direction. Executive function and learning/memory were most strongly predictive of levels of medication adherence achieved, whereas higher levels of adherence were predictive of relative improvements in a wide range of frontostriatal brain functions including processing speed, attention, executive functions, and motor functioning.
Conclusions:
These data provide evidence that cognition and adherence are reciprocally related in HIV/AIDS. In particular, executive dysfunction may play a key role in this relationship. Interventions aimed at improving or preserving executive functions could hold promise for interrupting progressive declines in adherence and neurocognitive ability in HIV/AIDS.
GLOSSARY
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= highly active antiretroviral therapy;
= Medication Event Monitoring System;
= protease inhibitor.
doi:10.1212/WNL.0b013e3181d8c1ca
PMCID: PMC2865732  PMID: 20220123
15.  CCL3 genotype and current depression increase risk of HIV-associated dementia 
Background
The prevalence of Human immunodeficiency virus (HIV)-associated dementia (HAD) has continued to rise even as incidence has fallen. Several host genetic variants have been identified that modify risk for HAD. However, the findings have not been replicated consistently and most studies did not consider the multitude of factors that might themselves confer risk for HAD. In the current study, we sought to replicate the findings of previous studies in a neurologically and behaviorally well-characterized cohort.
Methods
The sample consisted of 143 HIV+ individuals enrolled in the National NeuroAIDS Tissue Consortium (NNTC). Based on consensus diagnosis, 117 were considered neurologically normal upon study entry, and 26 had HAD. Seven single-nucleotide polymorphisms (SNPs) were genotyped within seven genes (CCL2, CCL3, CCL5, interleukin-1α [IL-1α], IL-10, stromal cell-derived factor 1, and tumor necrosis factor-α). Logistic regression analysis was used to predict group membership (normal vs HAD), with predictor variables including length of infection, age, current drug dependence, current depression, and genotype.
Results
The two groups were statistically similar with regards to demographic characteristics, current drug use, and disease factors. The HAD group had significantly greater number of individuals with current depression. Only one SNP, rs1130371 within the gene for CCL3, was entered into the analysis as the others showed symmetric distribution between groups. Logistic regression indicated that current depression and CCL3 genotype were significant predictors of HAD. Depression conferred a fivefold greater risk of HAD, while the TT genotype for CCL3 SNP (rs1130371) was associated with twofold risk for HAD.
Conclusion
Depression and CCL3 genotype predicted HAD. The fact that SNPs previously found to be associated with HAD were not in our analysis, and that rs1130371 is in high linkage disequilibrium with neighboring genes indicates that more dense genotyping in significantly larger cohorts is required to further characterize the relationship between genotype and risk for HAD.
PMCID: PMC2923399  PMID: 20725607
HIV-associated dementia; NeuroAIDS; CCL3; cytokine; depression; HIV
16.  Elements of attention in HIV-infected adults: Evaluation of an existing model 
Because of the multifactorial nature of neuropsychological tests, attention remains poorly defined from a neuropsychological perspective, and conclusions made regarding attention across studies may be limited due to the different nature of the measures used. Thus, a more definitive schema for this neurocognitive domain is needed. We assessed the applicability of Mirsky and Duncan's (2001) neuropsychological model of attention to a cohort of 104 HIV+ adults. Our analysis resulted in a five-factor structure similar to that of previous studies, which explained 74.5% of the variance. However, based on the psychometric characteristics of the measures comprising each factor, we offer an alternative interpretation of the factors. Findings also indicate that one factor, which is generally not assessed in clinical neuropsychology settings, may be more predictive of real-world behaviors (such as medication adherence) than those composed of traditional measures. Suggestions for further research in this important area are discussed.
doi:10.1080/13803390601186684
PMCID: PMC2886732  PMID: 17852595
17.  An exploratory study of long-term neurocognitive outcomes following recovery from opportunistic brain infections in HIV+ adults 
Central nervous system opportunistic infections (CNS-OI) are a significant cause of morbidity and mortality in AIDS. While current interventions are increasingly successful in treating CNS-OI, little information exists regarding long-term behavioral outcomes among survivors. In this exploratory study we examined neurocognitive data among three groups of adults with different AIDS-related CNS-OI: 15 with past cryptococcal meningitis (CM), 8 with toxoplasmosis encephalitis (TE), and 8 with progressive multifocal leukoencephalopathy (PML). A group of 61 individuals with AIDS, but without CNS-OI, was used as a comparison group. A battery of standardized neuropsychological tests assessing a variety of cognitive domains was administered upon entry. Results indicate that individuals with a history of CNS-OI were most impaired on measures of cognitive and psychomotor speed relative to the HIV+ comparison group. Among the CNS-OI groups, individuals with history of TE had the most severe and varied deficits. The results are discussed in relation to what is known about the neuropathological consequences of the various CNS-OIs. While this is the first systematic group study of residual CNS-OI effects on neurocognitive function, future studies employing more participants, perhaps focusing on specific CNS-OIs, will further characterize the long-term outcomes in AIDS-related CNS-OI.
doi:10.1080/13803390701819036
PMCID: PMC2886735  PMID: 18608693
Opportunistic infection; AIDS; Neuropsychological functioning; Toxoplasmosis encephalitis; Progressive multifocal leukoencephalopathy; Cryptococcal meningitis
18.  Neurocognition in Individuals Co-Infected with HIV and Hepatitis C 
Journal of addictive diseases  2008;27(2):11-17.
Due to similar routes of viral transmission, many individuals infected with the human immunodeficiency virus (HIV) are also infected with the hepatitis C virus (HCV). Each virus can cause cognitive compromise among mono-infected individuals; evidence is accumulating that HIV/HCV co-infection may have a particularly deleterious impact on cognition. We present neuropsychological data obtained from 118 HIV+ adults with advanced HIV disease, 35 of whom were co-infected with HCV, who completed a comprehensive neurocognitive evaluation. Rates of global cognitive impairment were higher among co-infected patients than among those with HIV alone (63% vs. 43%). Within the specific domains of learning and memory, co-infected individuals were significantly more likely to be impaired than were the HIV mono-infected participants. Finally, we discuss implications of these findings and potential future directions for research in this area.
PMCID: PMC2886797  PMID: 18681187
HIV infection; HCV infection; HIV/HCV co-infection; neurocognition
19.  Relationship between psychiatric status and frontal–subcortical systems in HIV-infected individuals 
Human immunodeficiency virus (HIV)-infected adults frequently evidence both neurocognitive and psychiatric dysfunction. It was hypothesized that apathy and irritability, but not anxiety and depression, are related to HIV effects on frontal–subcortical systems. This hypothesis was evaluated by determining the degree to which these psychiatric features are associated with neurocognitive functioning that is dependent upon frontal–subcortical circuitry and, therefore, thought to be sensitive to the central nervous system effects of HIV. Rating scales assessing irritability, apathy, depression, and anxiety and a dual-task paradigm were administered to 189 HIV-seropositive (HIV+) and 53 HIV-seronegative participants. Deficits in dual-task performance and greater anxiety, depression, apathy, and irritability were observed in HIV+ participants. Simultaneous multivariate regression and communality analyses revealed that only apathy and irritability were associated with dual-task performance in HIV+ participants. Thus, these findings suggest that apathy and irritability, but not depression and anxiety, are likely associated with the effects of HIV on frontal–subcortical circuitry.
doi:10.1017/S135561770707066X
PMCID: PMC2880510  PMID: 17445305
Human immunodeficiency virus; Apathy; Irritability; Depression; Anxiety; Cognition
20.  Neuropsychological Aspects of Coinfection with HIV and Hepatitis C Virus 
Infection with hepatitis C virus (HCV) is commonly seen in persons with human immunodeficiency virus (HIV) infection, because the viruses share risk factors for transmission; coinfection is a leading cause of morbidity and mortality among HIV-infected persons. Neuropsychological consequences of HIV infection are well established, and studies of HCV-infected persons have revealed neuropsychiatric dysfunction in this population as well. Investigators now are focusing on neuropsychological sequelae of coinfection with HIV and HCV, and preliminary results suggest that coinfection has a possible deleterious effect on global cognitive functioning consistent with frontal-subcortical dysfunction. Data on neuropsychiatric symptoms in coinfected persons are inconclusive at this time and are complicated by important differences in study populations (e.g., injection drug use and disease severity). This review summarizes what is known about neuropsychological aspects of monoinfection with HIV and HCV, as well as coinfection, discusses implications of these findings, and suggests future directions for this research area.
doi:10.1086/429494
PMCID: PMC2879257  PMID: 16265612
21.  The Item-Specific Deficit Approach to evaluating verbal memory dysfunction: Rationale, psychometrics, and application 
In the current study, we introduce the Item-Specific Deficit Approach (ISDA), a novel method for characterizing memory process deficits in list-learning data. To meet this objective, we applied the ISDA to California Verbal Learning Test (CVLT) data collected from a sample of 132 participants (53 healthy participants and 79 neurologically compromised participants). Overall, the ISDA indices measuring encoding, consolidation, and retrieval deficits demonstrated advantages over some traditional indices and indicated acceptable reliability and validity. Currently, the ISDA is intended for experimental use, although further research may support its utility for characterizing memory impairments in clinical assessments.
doi:10.1080/13803390802508918
PMCID: PMC2879263  PMID: 19142773
Memory; Psychometrics; Brain injury; Traumatic brain injury; Human immunodeficiency virus
22.  Functional Consequences of HIV-Associated Neuropsychological Impairment 
Neuropsychology review  2009;19(2):186-203.
This review focuses on the “real world” implications of infection with HIV/AIDS from a neuropsychological perspective. Relevant literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment, driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical, cognitive, psychosocial, and psychiatric issues on whether someone with HIV/AIDS will be able to return to work, adhere to a complicated medication regimen, or safely drive a vehicle will be discussed. Methodological issues that arise in the context of measuring medication adherence or driving capacity are also explored. Finally, the impact of HIV/AIDS on mood state, fatigue, and interpersonal relationships are addressed, with particular emphasis on how these variables interact with cognition and independent functioning. The purpose of this review is to integrate neuropsychological findings with their real world correlates of functional behavior in the HIV/AIDS population.
doi:10.1007/s11065-009-9095-0
PMCID: PMC2871666  PMID: 19472057
HIV/AIDS; Neuropsychology; Medication adherence; Employment; Driving
23.  Drug Use and Medication Adherence among HIV-1 Infected Individuals 
AIDS and behavior  2007;11(2):185-194.
This longitudinal study examined the impact of drug use and abuse on medication adherence among 150 HIV-infected individuals, 102 who tested urinalysis positive for recent illicit drug use. Medication adherence was tracked over a 6-month period using an electronic monitoring device (MEMS caps). Over the 6-month study drug-positive participants demonstrated significantly worse medication adherence than did drug-negative participants (63 vs. 79%, respectively). Logistic regression revealed that drug use was associated with over a fourfold greater risk of adherence failure. Stimulant users were at greatest risk for poor adherence. Based upon within-participants analyses comparing 3-day adherence rates when actively using versus not using drugs, this appears to be more a function of state rather than trait. These data suggest that it is the acute effects of intoxication, rather than stable features that may be characteristic of the drug-using populace, which leads to difficulties with medication adherence.
doi:10.1007/s10461-006-9152-0
PMCID: PMC2867605  PMID: 16897351
HIV infection; AIDS; Medication adherence; Drug use; Methamphetamine; Cocaine
24.  NEUROCOGNITIVE FUNCTIONING IN HIV-1 INFECTION: EFFECTS OF CEREBROVASCULAR RISK FACTORS AND AGE 
The Clinical neuropsychologist  2010;24(2):265-285.
This study examined the interactive effects of cerebrovascular risks, advancing age, and HIV infection on neurocognition, and explored whether pharmacological treatment of cerebrovascular risk factors attenuated neurocognitive dysfunction. Participants included 98 HIV-seropositive adults (cerebrovascular risk: 23.5%; age >50: 27.6%). Cerebrovascular risk was associated with slower processing speed even after controlling for age effects (b = −2.071; p = .04), and the interaction of age and cerebrovascular risk was associated with poorer verbal fluency (b = 1.276, p = .002). Participants with pharmacologically untreated cerebrovascular risk demonstrated reduced processing speed, learning/memory, and executive functioning relative to those on medication. Poor cerebrovascular health confers significant risk for HIV+ individuals, and this effect may be of greater consequence than advancing age. The cognitive impact of risk appears to be more pronounced in the absence of adequate pharmacological treatment.
doi:10.1080/13854040903482830
PMCID: PMC2863992  PMID: 20162495
Cerebrovascular; HIV/AIDS; Neurocognitive; Aging
25.  The generalizability of neurocognitive test/retest data derived from a nonclinical sample for detecting change among two HIV+ cohorts 
Objective methods for determining clinically relevant neurocognitive change are useful for clinicians and researchers, but the utility of such methods requires validation studies in order to assess their accuracy among target populations. We examined the generalizability of regression equations and reliable change indexes (RCI) derived from a healthy sample to two HIV-infected samples, one similar in demographic makeup to the normative group and the other dissimilar. Measures administered at baseline and follow-up included the Trail Making Test, Controlled Oral Word Association Test (COWAT), Grooved Pegboard, and Digit Span. Frequencies of decline, improvement, or stability were determined for each measure. Among the demographically similar clinical cohort, elevated rates of decline among more immunologically impaired participants were indicated by simple regression method on measures of psychomotor speed and attention, while RCI addressing practice effects (RCI-PE) indicated improvement on most measures regardless of immunostatus. Conversely, among the demographically dissimilar cohort, simple regression indicated high rates of decline across all measures, while RCI-PE indicated elevated rates of decline on psychomotor and attention measures. Thus, the accuracy of the two methods examined for determining clinically significant change among HIV+ cohorts differs depending upon their similarity with the normative sample.
doi:10.1080/13803390600920471
PMCID: PMC2863993  PMID: 17691040

Results 1-25 (33)