Despite immune recovery in individuals on combination antiretroviral therapy (CART), the frequency of HIV-associated neurocognitive disorders (HANDs) remains high. Immune recovery is typically achieved after initiation of ART from the nadir, or the lowest historical CD4. The present study evaluated the probability of neuropsychological impairment (NPI) and HAND as a function of CD4 nadir in an HIV-positive cohort.
One thousand five hundred and twenty-five HIV-positive participants enrolled in CNS HIV Antiretroviral Therapy Effects Research, a multisite, observational study that completed comprehensive neurobehavioral and neuromedical evaluations, including a neurocognitive test battery covering seven cognitive domains. Among impaired individuals, HAND was diagnosed if NPI could not be attributed to comorbidities. CD4 nadir was obtained by self-report or observation. Potential modifiers of the relationship between CD4 nadir and HAND, including demographic and HIV disease characteristics, were assessed in univariate and multivariate analyses.
The median CD4 nadir (cells/μl) was 172, and 52% had NPI. Among impaired participants, 603 (75%) had HAND. Higher CD4 nadirs were associated with lower odds of NPI such that for every 5-unit increase in square-root CD4 nadir, the odds of NPI were reduced by 10%. In 589 virally suppressed participants on ART, higher CD4 nadir was associated with lower odds of NPI after adjusting for demographic and clinical factors.
As the risk of NPI was lowest in patients whose CD4 cell count was never allowed to fall to low levels before CART initiation, our findings suggest that initiation of CART as early as possible might reduce the risk of developing HAND, the most common source of NPI among HIV-infected individuals.
CD4 nadir; combination antiretroviral therapy; HIV-associated; neurocognitive disorders; neurocognitive impairment
The present study assesses the impact of methamphetamine (METH) on antiretroviral (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors (i.e., major depressive disorder (MDD), Antisocial Personality Disorder (ASPD), and Attention Deficit Disorder (ADHD)) for ART nonadherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+/METH+; n = 67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+/METH−; n = 50). Ancillary analyses compared these groups with a small group of HIV+/METH+ persons with current METH abuse/dependence (HIV+/CU METH+; n = 8). Nonadherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH− participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART nonadherence (p’s<0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART nonadherence after controlling for the other variables (p<0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of nonadherence) than lifetime METH+ users and HIV+/METH-participants, and that neurocognitive impairment was associated with nonadherence (p’s<0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication nonadherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may also need to address coexisting neuropsychiatric factors and cognitive impairment to improve ART medication taking.
HIV/AIDS; Cognition; Medication Adherence; Antiretroviral; Methamphetamine
Standard methods used to estimate HIV-1 population diversity are often resource intensive (e.g., single genome amplification, clonal amplification and pyrosequencing) and not well suited for large study cohorts. Additional approaches are needed to address the relationships between intraindividual HIV-1 genetic diversity and disease. With a small cohort of individuals, we validated three methods for measuring diversity: Shannon entropy and average pairwise distance (APD) using single genome sequences, and counts of mixed bases (i.e. ambiguous nucleotides) from population-based sequences. In a large cohort, we then used the mixed base approach to determine associations between measure HIV-1 diversity and HIV associated disease. Normalized counts of mixed bases correlated with Shannon Entropy at both the nucleotide (rho=0.72, p=0.002) and amino acid level (rho=0.59, p=0.015), and APD (rho=0.75, p=0.001). Among participants who underwent neuropsychological and clinical assessments (n=187), increased HIV-1 population diversity was associated with both a diagnosis of AIDS and neuropsychological impairment.
HIV; AIDS; genetic diversity; neuropsychological impairment; viral population dynamics
While performance-based tests of everyday functioning offer promise in facilitating diagnosis and classification of HIV-associated neurocognitive disorders (HAND), there remains a dearth of well-validated instruments. In the present study, clinical correlates of performance on one such measure (i.e., Medication Management Test—Revised; MMT-R) were examined in 448 HIV+ adults who were prescribed antiretroviral therapy. Significant bivariate relationships were found between MMT-R scores and demographics (e.g., education), hepatitis C co-infection, estimated premorbid IQ, neuropsychological functioning, and practical work abilities. MMT-R scores were not related to HIV disease severity, psychiatric factors, or self-reported adherence among participants with a broad range of current health status. However, lower MMT-R scores were strongly and uniquely associated with poorer adherence among participants with CD4 T-cell counts <200. In multivariate analyses, MMT-R scores were predicted by practical work abilities, estimated premorbid functioning, attention/working memory, learning, and education. Findings provide overall mixed support for the construct validity of the MMT-R and are discussed in the context of their clinical and research implications for evaluation of HAND.
HIV; medication management; neuropsychological functioning; adherence; construct validity; instrumental activities of daily living
The Social Security Administration is considering whether schizophrenia may warrant inclusion in their new “Compassionate Allowance” process, which aims to identify diseases and other medical conditions that almost always qualify for Social Security disability benefits simply on the basis of their confirmed presence. This paper examines the reliability and validity of schizophrenia diagnosis, how a valid diagnosis is established, and the stability of the diagnosis over time. A companion paper summarizes evidence on the empirical association between schizophrenia and disability, thus leading to this paper that evaluates how valid clinical diagnoses of schizophrenia are.
Literature review and synthesis, based on a workplan developed in an expert meeting convened by the National Institute of Mental Health and the Social Security Administration.
At least since the introduction of the 3rd edition of the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-III) in 1980, diagnoses of schizophrenia made by mental health specialists are valid, reliable, and stable over time, across community as well as academic practice settings, and across different assessment methods. These analyses are particularly valid during the time-frame relevant to social security awards: at least two years after the initial stages of illness. We could not find studies that have evaluated the validity or reliability of schizophrenia diagnoses made by exclusively by primary care providers (vs. mental health professionals).
In the post-DSM-III era, schizophrenia diagnosis – using modern diagnostic criteria – is valid and reliable when performed by doctoral-level mental health specialists (i.e., psychiatrists and psychologists), in community as well as academic settings.
The Social Security Administration (SSA) is considering whether schizophrenia may warrant inclusion in their new “Compassionate Allowance” process, which aims to identify diseases and other medical conditions that invariably quality for Social Security disability benefits and require no more than minimal objective medical information. This paper summarizes evidence on the empirical association between schizophrenia and vocational disability. A companion paper examines the reliability and validity of schizophrenia diagnosis which is critically relevant for granting a long-term disability on the basis of current diagnosis.
This is a selective literature review and synthesis, based on a work plan developed in a meeting of experts convened by the National Institute of Mental Health and the SSA. This review of the prevalence of disability is focused on the criteria for receipt of disability compensation for psychotic disorders currently employed by the SSA.
Disability in multiple functional domains is detected in nearly every person with schizophrenia. Clinical remission is much more common than functional recovery, but most patients experience occasional relapses even with treatment adherence, and remissions do not predict functional recovery. Under SSA’s current disability determination process, approximately 80% of SSDI/SSI applications in SSA’s diagnostic category of “Schizophrenia/Paranoid Functional Disorders” are allowed, compared to around half of SSDI/SSI applications overall. Moreover, the allowance rate is even higher among applicants with schizophrenia. Many unsuccessful applicants are not denied, but rather simply are unable to manage the process of appeal after initial denials.
Research evidence suggests that disability applicants with a valid diagnosis of schizophrenia have significant impairment across multiple dimensions of functioning, and will typically remain impaired for the duration of normal working ages or until new interventions are developed.
Among English-speaking adults, HIV-associated neuropsychological (NP) impairments have been associated with problems in everyday functioning, including ability to function at work and drive an automobile. Latinos account for a disproportionate number of HIV/AIDS cases nationwide, and a significant segment of this population is primarily Spanish speaking. We have previously developed an assessment that evaluates English-speakers on a variety of instrumental activities of daily living. In this pilot study, we used Spanish-language translations of our functional battery to investigate the cultural relevance of such measures, and to explore relationships between NP status and ability to perform important everyday tasks in HIV-infected Spanish-speakers. Sixteen HIV-infected monolingual Spanish-speaking adults received comprehensive, Spanish language NP testing and functional assessments included the following domains: Medication Management, Cooking, Finances, Shopping, and Restaurant Scenario. Results revealed that most of the functional tasks appeared culturally relevant and appropriate with minor modifications. NP-impaired participants were significantly more functionally impaired compared to NP-normals (88% vs. 13%, p<.01). Performances on the functional assessment and the NP battery were also related to indicators of real world functioning, including employment status and quality of life. These results, though preliminary, suggest that Spanish language functional assessments are potentially valid tools for detecting everyday functioning deficits associated with NP impairments in HIV-infected Spanish-speakers.
Neuropsychological disturbances have been reported in association with use of the recreational drug “ecstasy,” or 3,4-methylenedioxymethamphetamine (MDMA), but findings have been inconsistent. We performed comprehensive neuropsychological testing examining seven ability domains in 21 MDMA users (MDMA+) and 21 matched control participants (MDMA−). Among MDMA+ participants, median [interquartile range] lifetime MDMA use was 186 [111, 516] doses, with 120 [35–365] days of abstinence. There were no significant group differences in neuropsychological performance, with the exception of the motor speed/dexterity domain in which 43% of MDMA+ were impaired compared with 5% of MDMA− participants (p = .004). Motor impairment differences were not explained by use of other substances and were unrelated to length of abstinence or lifetime number of MDMA doses. Findings provide limited evidence for neuropsychological differences between MDMA+ and MDMA− participants with the exception of motor impairments observed in the MDMA+ group. However, replication of this finding in a larger sample is warranted.
Ecstasy; N-Methyl-3; 4-methylenedioxyamphetamine; Neurocognitive; Neurotoxicity; Stimulant; Hallucinogen
Cognitive deficits are associated with disability in people with schizophrenia so treatment of cognitive impairment has been proposed as an intervention to reduce disability. However, studies relying on patient self-report have found very minimal relationships between ratings of real-world functioning and cognitive performance, raising questions about the measurement of real-world functioning as a treatment outcome. The Validation of Everyday Real-world Outcomes (VALERO) study was conducted to evaluate functional rating scales and to identify the rating scale or scales most robustly related to performance-based measures of cognition and everyday living skills.
198 adults with schizophrenia were tested with the neurocognitive measures from the MATRICS Consensus cognitive Battery and performed the UCSD performance-based skills assessment-Brief and advanced finances subtest from the Everyday Functioning Battery. They and a friend, relative, clinician, or case manager also reported their everyday functioning on 6 ratings scales: Social Behavior Schedule, Social Adjustment Scale, Heinrichs Carpenter Quality of Life Scale, Specific Levels of Functioning, Independent Living skills Survey, and Life Skills Profile. Best judgment ratings were generated by an interviewer who administered the rating scales to patients and informants.
Statistical analyses developed an ability latent trait that reflected scores on the three performance-based (i.e., ability) measures and canonical correlation analysis related interviewer ratings to the latent trait. The overall fit of the model with all six rating scales was good: χ2 = 78.100, df = 56, p = .027, and RMSEA = .078. Individual rating scales that did not improve the fit of the model were systematically deleted and a final model with two rating scales fit the data: χ2 = 32.059, df = 24, p = .126, RMSEA = .072. A regression analysis found that the Specific Levels of Functioning was a superior predictor of the three-performance based ability measures.
We found that systematic assessments of real world functioning are related to performance on neurocognitive and functional capacity measures. Of the six rating scales evaluated, the Specific Levels of Functioning (SLOF) was best in this study. Use of a single rating scale provides a very efficient assessment of real-world functioning that accounts for considerable variance in performance-based scores.
Recent advances in the assessment of disability in schizophrenia have separated the measurement of functional capacity (the ability to perform everyday functioning skills in structured assessments) from real-world functional outcomes. This study examined the similarity of performance-based assessments of everyday functioning, real-world disability, and achievement of milestones in people with schizophrenia in the United States and in Sweden.
Samples of schizophrenia patients living in rural areas in Sweden (n=146) and in New York (n=244)) performed the brief version of the UCSD Performance-based Skills Assessment (UPSA-B) and a neuropsychological assessment and were rated for functioning by their case managers. Information from records and case managers was used to determine the frequency of living independently, working, and having ever experienced a stable romantic relationship.
Performance on the UPSA-B was essentially identical in the two samples (New York, M=13.84; Sweden, M=13.30). So were scores on the case manager ratings of everyday activities (New York: M=49.0; Sweden: M=48.8). The correlations between UPSA-B scores, NP test performance, and SLOF ratings did not differ across the two samples. The proportion of cases who had never had a close relationship and rates of vocational disability were also nearly identical. In contrast, 80% of the Swedish patients and 46% of the New York patients were living independently.
Scores on performance-based measures of everyday living skills were very similar in people with schizophrenia across cultures. In contrast, real-world residential outcomes were very different. These data suggest that cultural and social support systems can lead to divergent real-world outcomes in individuals who have evidence of the same levels of ability and potential.
The aim of the current study was to develop and validate demographically-adjusted normative standards for the HIV Dementia Scale (HDS). Given the association between demographic variables and the HDS summary score, demographically-adjusted normative standards may enhance the classification accuracy of the HDS. Demographically-adjusted normative standards were derived from a sample of 182 seronegative healthy participants and were subsequently applied to a sample of 135 HIV-1 seropositive individuals with multidisciplinary case conference diagnoses of HIV-1-associated neurocognitive disorders (e.g., HIV-1-associated dementia and Minor-Cognitive/Motor Disorder) in proportions consistent with published epidemiologic reports. In the normative sample, age and education (and their interaction) emerged as the only demographic factors significantly associated with the HDS. In comparison to the traditional HDS cut score (raw score total ≤10), use of the demographically-adjusted normative standards significantly improved the sensitivity (from 17.2% to 70.7%, respectively) and overall classification accuracy (increasing the odds ratio from 3 to approximately 6) of the HDS for identifying participants with HIV-1-associated neurocognitive disorders. The application of demographically-adjusted normative standards on the HDS improves the clinical applicability and accuracy of this cognitive screening measure in the detection of HIV-1-associated neurocognitive disorders.
Human immunodeficiency virus; Screening Tests; Dementia; Neuropsychological Assessment
Despite multiple lines of evidence suggesting that people with schizophrenia have substantial problems in self-reporting everyday functioning and cognitive performance, self-report methods are still widely used to assess functioning. This study attempted to identify predictors of accuracy in self report, both in terms of accurate self-assessment and over-estimation of current functioning. As part of the larger Validating Assessments of Everyday Real-World Outcomes (VALERO) study, 195 patients with schizophrenia were asked to self report their everyday functioning with the Specific Levels of Functioning (SLOF) scale, which includes subscales assessing social functioning, everyday activities, and vocational functioning. They were also assessed with measures of neuropsychological (NP) performance and functional capacity (FC), and were assessed for psychiatric symptomatology. In addition, a friend, relative or clinician informant was interviewed with the SLOF, and an interviewer with access to all information provided by the patient and informant (exclusive of performance-based data) generated “best estimate” ratings of actual, everyday functioning. Patients significantly (p<.001) overestimated their vocational functioning and everyday activities compared to the interviewer judgments. Lower levels of NP and FC performance and everyday functioning on the part of patients were consistently associated with overestimation of their functioning. Patient self-reports were not correlated with any performance-based measures, while interviewer judgments were significantly correlated with patients’ performance on NP and FC measures (p<.005). In regression analyses, adjusting for interviewer ratings of functioning, several predictors of the discrepancy between self and interviewer judgments emerged. Higher levels of depressive symptoms were associated with less overestimation in self-reports (p<.001). Delusions, suspiciousness, grandiosity and poor rapport were all significantly (p<.001) associated with over-estimation of functioning compared to interviewer judgments. Poorer NP and FC performance were also associated with over-estimation of everyday functioning, but these results were not statistically significant in multivariate regression models. Consistent with previous studies in schizophrenia, other neuropsychiatric conditions and non-clinical populations, higher levels of depression were associated with increased accuracy in self-assessment. Similarly, lower scores on performance-based measures and judgments of everyday functioning also predicted over-estimation of functioning. Thus, we identified bi-directional predictors of mis-estimation of everyday functioning, even when poor baseline scores were considered. These data suggest that it may be possible to screen patients for their ability to self-report their functioning, but that performance-based measures of functioning provide a less biased assessment.
Little is known about the medical status of individuals entering treatment for co-occurring substance abuse and other mental disorders (COD). We analyzed the medical histories of 169 adults entering outpatient treatment for CODs, estimating lifetime prevalence of chronic illness and current smoking, comparing these rates to the general population, and examining psychiatric and substance-related correlates of chronic illness. Results revealed significantly higher prevalence of hypertension, asthma, arthritis, and smoking compared to the general US population, and showed an association between chronic illness and psychiatric symptom distress and substance use severity. Findings support integration of chronic illness management into COD treatment.
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.
Neuropsychology; HIV; Aging; Functional abilities; Medication management; Finance management
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.
Depression; Self-report; Functional ability; Cognition; HIV
Treatments for the cognitive impairments of schizophrenia are urgently needed. We developed and tested a 12-week, group-based, manualized, Compensatory Cognitive Training (CCT) intervention targeting prospective memory, attention, learning/memory, and executive functioning. The intervention focused on compensatory strategies such as calendar use, self-talk, note-taking, and a six-step problem-solving method, and did not require computers.
In a randomized controlled trial, 69 outpatients with DSM-IV primary psychotic disorders were assigned to receive standard pharmacotherapy (SP) alone or CCT + SP for 12 weeks. Assessments of neuropsychological performance and functional capacity (primary outcomes) and psychiatric symptom severity, quality of life, social skills performance, cognitive insight, and self-reported everyday functioning (secondary outcomes) were administered at baseline, post-treatment, and 3-month follow-up. Data were collected between September 2003 and August 2009.
Hierarchical linear modeling analyses demonstrated significant CCT-associated effects on attention at follow-up (p=0.049), verbal memory at post-treatment and follow-up (ps≤0.039), and functional capacity (UCSD Performance-based Skills Assessment) at follow-up (p=0.004). The CCT group also differentially improved in negative symptom severity at post-treatment and follow-up (ps≤0.025) and subjective quality of life at follow-up (p=0.002).
Compensatory Cognitive Training, a low-tech, brief intervention, has the potential to improve not only cognitive performance, but also functional skills, negative symptoms, and self-rated quality of life in people with psychosis.
schizophrenia; rehabilitation; cognitive remediation; memory
The present study aimed to examine if bilingualism affects executive functions and verbal fluency in Marathi and Hindi, two major languages in India, with a considerable cognate (e.g., activity is actividad in Spanish) overlap. A total of 174 native Marathi speakers from Pune, India, with varying levels of Hindi proficiency were administered tests of executive functioning and verbal performance in Marathi. A bilingualism index was generated using self-reported Hindi and Marathi proficiency. After controlling for demographic variables, the association between bilingualism and cognitive performance was examined. Degree of bilingualism predicted better performance on the switching (Color Trails-2) and inhibition (Stroop Color-Word) components of executive functioning; but not for the abstraction component (Halstead Category Test). In the verbal domain, bilingualism was more closely associated with noun generation (where the languages share many cognates) than verb generation (which are more disparate across these languages), as predicted. However, contrary to our hypothesis that the bilingualism “disadvantage” would be attenuated on noun generation, bilingualism was associated with an advantage on these measures. These findings suggest distinct patterns of bilingualism effects on cognition for this previously unexamined language pair, and that the rate of cognates may modulate the association between bilingualism and verbal performance on neuropsychological tests.
Multilingualism; Neuropsychological tests; India; Adult; Executive functions; Cognition
Estimates of the prevalence of lifetime suicidal ideation and attempt, and risks for new-onset suicidality, among HIV-infected (HIV+) individuals are not widely available in the era of modern combined antiretroviral treatment (cART).
Participants (n=1560) were evaluated with a comprehensive battery of tests that included the depression and substance use modules of the Composite International Diagnostic Interview (CIDI) and the Beck Depression Inventory-II (BDI-II) as part of a large prospective cohort study at six U.S. academic medical centers. Participants with possible lifetime depression (n=981) were classified into five categories: 1) no thoughts of death or suicide (n=352); 2) thoughts of death (n=224); 3) thoughts of suicide (n=99); 4) made a suicide plan (n=102); and 5) attempted suicide (n=204).
Twenty-six percent (405/1560) of participants reported lifetime suicidal ideation and 13% (204/1560) reported lifetime suicide attempt. Participants who reported suicidal thoughts or plans, or attempted suicide, reported higher scores on the BDI-II (p<0.0001), and higher rates of current major depressive disorder (p=0.01), than those who did not. Attempters reported higher rates of lifetime substance abuse (p=0.02) and current use of psychotropic medications (p=0.01) than non-attempters.
Study assessments focused on lifetime, rather than current, suicide. Data was not collected on the timing of ideation or attempt, frequency, or nature of suicide attempt.
High rates of lifetime suicidal ideation and attempt, and the relationship of past report with current depressed mood, suggests that mood disruption is still prevalent in HIV. Findings emphasize the importance of properly diagnosing and treating psychiatric comorbidities among HIV persons in the cART era.
HIV; depression; suicide
Chronic use of methamphetamine (MA) has moderate effects on neurocognitive functions associated with frontal systems, including the executive aspects of verbal episodic memory. Extending this literature, the current study examined the effects of MA on visual episodic memory with the hypothesis that a profile of deficient strategic encoding and retrieval processes would be revealed for visuospatial information (i.e., simple geometric designs), including possible differential effects on source versus item recall.
The sample comprised 114 MA-dependent (MA+) and 110 demographically-matched MA-nondependent comparison participants (MA−) who completed the Brief Visuospatial Memory Test – Revised (BVMT-R), which was scored for standard learning and memory indices, as well as novel item (i.e., figure) and source (i.e., location) memory indices.
Results revealed a profile of impaired immediate and delayed free recall (p < .05) in the context of preserved learning slope, retention, and recognition discriminability in the MA+ group. The MA+ group also performed more poorly than MA− participants on Item visual memory (p < .05) but not Source visual memory (p > .05), and no group by task-type interaction was observed (p > .05). Item visual memory demonstrated significant associations with executive dysfunction, deficits in working memory, and shorter length of abstinence from MA use (p < 0.05).
These visual memory findings are commensurate with studies reporting deficient strategic verbal encoding and retrieval in MA users that are posited to reflect the vulnerability of frontostriatal circuits to the neurotoxic effects of MA. Potential clinical implications of these visual memory deficits are discussed.
Methamphetamine; neuropsychological assessment; encoding; episodic memory; frontal lobe
To determine how serious a confound substance use (SU) might be in studies on HIV-associated neurocognitive disorder (HAND) we examined the relationship of SU history to neurocognitive impairment (NCI) in participants enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study.
After excluding cases with behavioral evidence of acute intoxication and histories of factors that independently could account for NCI (e.g., stroke), baseline demographic, medical, SU, and neurocognitive data were analyzed from 399 participants. Potential SU risk for NCI was determined by the following criteria: lifetime SU DSM-IV diagnosis, self-report of marked lifetime SU, or positive urine toxicology (UTOX). Participants were divided into three groups: no SU (N = 134), Non-syndromic SU (N = 131), syndromic SU (N = 134) and matched on literacy level, nadir CD4, and depressive symptoms.
While approximately 50% of the participants were diagnosed with HAND, a MANCOVA of neurocogntive summary scores, covarying for UTOX, revealed no significant effect of SU status. Correlational analyses indicated weak associations between lifetime heroin dosage and poor recall and working memory, as well as between cannabis and cocaine use and better verbal fluency.
These data indicate that HIV neurocognitive effects are seen at about the same frequency in those with and without historic substance abuse, in cases that are equated on other factors that might contribute to NCI. Therefore, studies on neuroAIDS and its treatment need not exclude such cases. However, the effects of acute SU and current SU disorders on HAND require further study.
Substance use; HIV-associated neurocognitive disorder; cognition
Self reports of everyday functioning on the part of people with schizophrenia have been found to be poorly correlated with the reports of other informants and with their own performance of tests of cognition and functional abilities. However, it is not clear which informants are best for providing accurate reports of everyday functioning. This study examined the convergence between self-reports on the part of people with schizophrenia (n=193), who real-world functioning was rated by a friend or relative (n=154), or a high contact clinician (n=39) across 6 functional status rating scales. In addition, correlations between these reports and patient’s performance on neuropsychological tests and a performance-based measure of functional capacity were also calculated. For convergence between raters, friend or relative informants and patient reports were significantly correlated for 4/6 rating scales. For the smaller sample of clinician informants, the correlations were significant on 2/6 scales. In the analyses of convergence between patient performance scores and functioning ratings, only 1/12 correlations between patient report and performance were significant, while friend or relative reports also were only correlated with performance on one rating scale. In contrast, clinician reports of functioning were correlated with patients’ functional capacity performance on 4/6 rating scales and with neuropsychological test performance on 2/6. High contact clinicians appear to generate ratings of everyday functioning that are more closely linked to patients’ ability scores than friend or relative informants. Later analyses will determine if there are differences between friend or relative informants.
Script generation describes one’s ability to produce complex, sequential action plans derived from mental representations of everyday activities. The aim of this study was to assess the effect of HIV infection on script generation performance. Sixty HIV+ individuals (48% of whom had HIV-associated neurocognitive disorders [HAND]) and 26 demographically comparable HIV− participants were administered a novel, standardized test of script generation, which required participants to verbally generate and organize the necessary steps for completing six daily activities. HAND participants evidenced significantly more total errors, intrusions, and script boundary errors compared to the HIV-sample, indicating difficulties inhibiting irrelevant actions and staying within the prescribed boundaries of scripts, but had adequate knowledge of the relevant actions required for each script. These findings are generally consistent with the executive dysfunction and slowing common in HAND and suggest that script generation may play a role in everyday functioning problems in HIV.
Human immunodeficiency virus; cognition; neuropsychology; activities of daily living; executive functions; frontal lobes
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 Test-Revised, 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, gender) in either race/ethnicity group. Findings support the need to consider extended demographic contributions to neuropsychological test performance in clinical and research settings.
A subset of individuals with HIV-associated neurocognitive impairment experience related deficits in “real world” functioning (i.e., independently performing instrumental activities of daily living [IADL]). While performance-based tests of everyday functioning are reasonably sensitive to HIV-associated IADL declines, questions remain regarding the extent to which these tests’ highly structured nature fully captures the inherent complexities of daily life. The aim of this study was to assess the predictive and ecological validity of a novel multitasking measure in HIV infection.
Participants included 60 individuals with HIV infection (HIV+) and 25 demographically comparable seronegative adults (HIV−). Participants were administered a comprehensive neuropsychological battery, questionnaires assessing mood and everyday functioning, and a novel standardized test of multitasking, which involved balancing the demands of four interconnected performance-based functional tasks (i.e., financial management, cooking, medication management, and telephone communication).
HIV+ individuals demonstrated significantly worse overall performance, fewer simultaneous task attempts, and increased errors on the multitasking test as compared to the HIV− sample. Within the HIV+ sample, multitasking impairments were modestly associated with deficits on standard neuropsychological measures of executive functions, episodic memory, attention/working memory, and information processing speed, providing preliminary evidence for convergent validity. More importantly, multivariate prediction models revealed that multitasking deficits were uniquely predictive of IADL dependence beyond the effects of depression and global neurocognitive impairment, with excellent sensitivity (86%), but modest specificity (57%).
Taken together, these data indicate that multitasking ability may play an important role in successful everyday functioning in HIV+ individuals.
HIV; cognition; neuropsychology; activities of daily living; executive functions