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
Reliable detection and quantification of longitudinal cognitive change are of considerable importance in many neurological disorders, particularly to monitor central nervous system effects of disease progression and treatment. In the current study, we developed normative data for repeated neuropsychological (NP) assessments (6 testings) using a modified Standard Regression-Based (SRB) approach in a sample that includes both HIV-uninfected (HIV−, N=172) and neuromedically stable HIV-infected (HIV+, N=124) individuals. Prior analyzes indicated no differences in NP change between the infected and uninfected participants. The norms for change included correction for factors found to significantly affect follow-up performance, using hierarchical regression. The most robust and consistent predictors of follow-up performance were the prior performance on the same test (which contributed in all models) and a measure of prior overall NP competence (predictor in 97% of all models). Demographic variables were predictors in 10%-46% of all models and in small amounts; while test retest interval contributed in only 6% of all models. Based on the regression equations, standardized change scores (z-scores) were computed for each test measure at each interval; these z scores were then averaged to create a total battery change score. An independent sample of HIV− participants who had completed 8 of the 15 tests was used to validate an abridged summary change score. The normative data are available in an electronic format by email request to the first author. Correction for practice effects based on normative data improved the consistency of NP impairment classification in a clinically stable longitudinal cohort after baseline.
Normative data; longitudinal studies; regression; regression change score; SRB; practice effect
China’s HIV epidemic commenced in its agrarian provinces through contaminated commercial plasma donation centers and is now becoming a public health concern nationwide. Little is known of the psychiatric and substance use disorder characteristics of this population, or their impact on everyday function, employment, and life quality.
HIV infected (HIV+) former plasma donors (N = 203) and HIV-negative (HIV-) donor controls (N = 198) completed the World Mental Health Survey Composite International Diagnostic Interview to determine lifetime major depressive disorder (MDD), substance use disorders, and suicidality. Current mood and suicidality were assessed with the Beck Depression Inventory-II. Everyday function was measured by an Activity of Daily Living questionnaire; life quality was evaluated by the Medical Outcomes Study-HIV.
According to the multi-process theory of prospective memory (ProM), time-based tasks rely more heavily on strategic processes dependent on prefrontal systems than do event-based tasks. Given the prominent frontostriatal pathophysiology of HIV infection, one would expect HIV-infected individuals to demonstrate greater deficits in time-based versus event-based ProM. However, the two prior studies examining this question have produced variable results. We evaluated this hypothesis in 143 individuals with HIV infection and 43 demographically similar seronegative adults (HIV−) who completed the research version of the Memory for Intentions Screening Test, which yields parallel subscales of time- and event-based ProM. Results showed main effects of HIV serostatus and cue type, but no interaction between serostatus and cue. Planned pair-wise comparisons showed a significant effect of HIV on time-based ProM and a trend-level effect on event-based ProM that was driven primarily by the subset of participants with HIV-associated neurocognitive disorders. Nevertheless, time-based ProM was more strongly correlated with measures of executive functions, attention/working memory, and verbal fluency in HIV-infected persons. Although HIV-associated deficits in time- and event-based ProM appear to be of comparable severity, the cognitive architecture of time-based ProM may be more strongly influenced by strategic monitoring and retrieval processes.
AIDS dementia complex; Episodic memory; Executive functions; Neuropsychological assessment
Background: People with schizophrenia demonstrate considerable discrepancy between self-reported functioning and informant reports. It is not clear whether these discrepancies originate from the instruments used or from the perspectives of different informants. The goal of the Validation of Everyday Real-World Outcomes (VALERO) Study is to enhance the measurement of real-world (RW) outcomes in the social, residential, and vocational domains through selection of optimal scales and informants using a multistep process similar to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. Methods: Forty-eight experts provided their opinion regarding the best scales measuring RW outcomes. Fifty-nine measures were nominated. The investigators selected the 11 scales that were the most highly nominated, had the most published validity data, and best represented the domains of interest. Information was provided to other experts who served as RAND panelists. Panelists rated each measure for its suitability across multiple a priori domains. Discrepant ratings were discussed until consensus was reached. Results: Following the RAND Panel, the 2 scales that scored highest across the various criteria for each of the classes of scales (hybrid, social functioning, and everyday living skills) were selected for use in the first substudy of VALERO. The scales selected were the Quality-of-Life Scale, Specific Levels of Functioning Scale, Social Behavior Schedule, Social Functioning Scale, Independent Living Skills Schedule, and Life Skills Profile. Discussion: The results show that although there are significant limitations with current scales used for the assessment of RW outcome in schizophrenia, a consensus is possible. Further, several existing instruments were rated as useful for measuring social, residential, and vocational outcomes.
schizophrenia; cognition; functional outcomes
Patients with obstructive sleep apnea (OSA) commonly have cognitive complaints. There are few randomized studies that have examined neuropsychological effects of continuous positive airway pressure (CPAP) treatment in patients with OSA. In this double-blind trial, we examined if a 3-week CPAP treatment compared with placebo CPAP treatment has specific therapeutic effects on cognitive impairments in patients with OSA and if there are specific domains of cognitive impairments sensitive to 3-week CPAP treatment.
Subjects and methods
Thirty-eight newly diagnosed patients with untreated OSA underwent neuropsychological testing before and after 3-weeks CPAP or Placebo CPAP treatment. The two treatment groups (therapeutic CPAP, and placebo-CPAP) were compared using repeated measures analysis of variance (ANOVA).
Results and conclusion
Impairments in neuropsychological functioning ranged from 2.6% to 47.1% before treatment. In response to 3 weeks of treatment, there was no significant time by treatment interaction for a global deficit score of neuropsychological functioning. Only the Stroop Color (number correct) test showed significant improvement specific to CPAP treatment. The study demonstrates the importance of further randomized placebo controlled studies in this area.
obstructive sleep apnea; CPAP; cognitive function; double blind placebo-controlled; neuropsychological test; Stroop color
Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent and 58 used MA at least once during the interval period. Thirty-eight non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities relative to the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.
Methamphetamine; dependence; drug abstinence; cognition; central nervous system; affective disorders
Host genetic factors are important determinants for risk of HIV-1 infection and disease progression. This study examined associations of host genetic variants and neurocognitive impairment in Chinese subjects infected through contaminated blood products.
201 HIV-infected subjects from Anhui, China had neuropsychological (NP) tests at baseline and 12 months. DNA was genotyped for APOE ε2, ε3 and ε4 alleles, MBL2-A/O,CCR5-wt/Δ32, CCR5-59029-G/A, CCR2-180-G/A, SDF-1-G/A, IL4-589-C/T, MCP-1-2518-A/G, CX3CR1-745-G/A, -849-C/T polymorphisms and CCL3L1 copy number variants (CNVs) using real-time PCR. Univariate and multivariate analyses were performed.
The cohort was 61% males, mean education: 5.5 years, AIDS diagnosis: 113(55%), on antiretrovirals: 114(56%), mean baseline CD4+ count: 349/mm3 and mean log10 RNA 4.09. At baseline, 37% had global NP impairment increasing to 44% after 12 months. Of 43 subjects with the APOE ε4 allele, 58% were cognitively impaired versus 31% without the ε4 allele (P=0.001, OR: 3.09; 95% CI: 1.54, 6.18). The mean GDS for ε4 positive participants on antiretrovirals for 12 months was 0.88 (0.55) versus 0.63 (.54) for ε4 negatives (P = 0.053, 95%CI: -0.004, 0.51). For MBL2, 52% of subjects with the O/O genotype declined in cognitive function over 12 months versus 23% with A/A (OR = 3.62. 95% CI: 1.46, 9.03; P=0.004). No associations were observed for the other genetic variants.
The APOE ε4 allele was associated with increased risk for cognitive deficits, while the MBL2 O/O genotype was associated with increased risk for progressive cognitive decline in Chinese subjects infected with HIV through contaminated blood products.
APOE; MBL-2; HIV; cognitive impairment; host genetics; China
Chronically institutionalized patients with schizophrenia have been reported to manifest cognitive and functional decline. Previous studies were limited by the fact that current environment could not be separated from life-time illness course. The present study examined older outpatients who varied in their lifetime history of long-term psychiatric inpatient stay.
Community dwelling patients with schizophrenia (n=111) and healthy comparison subjects (n=76) were followed up to 45 months and examined two or more times with a neuropsychological (NP) battery and performance-based measures of everyday living skills (UCSD Performance-based skills assessment; UPSA) and social competence. A mixed-effects model repeated-measures method was used to examine changes.
There was a significant effect of institutional stay on the course of the UPSA. When the schizophrenia patients who completed all three assessments were divided on the basis of length of institutional stay and compared to healthy comparison subjects, patients with longer stays worsened on the UPSA and social competence while patients with shorter stays improved. For NP performance, both patient samples worsened slightly while the HC group manifested a practice effect. Reliable change index (RCI) analyses showed that worsening on the UPSA for longer stay patients was definitely nonrandom.
Life-time history of institutional stay was associated with worsening on measures of social and everyday living skills. NP performance in schizophrenia did not evidence the practice effect seen in the HC sample. These data suggest that schizophrenia patients with a history of long institutional stay may worsen even if they are no longer institutionalized.
To quantify and characterize the nature of cognitive change over one year in a cohort of HIV+ former plasma donors in rural China.
Observational cohort study
192 HIV+ and 101 demographically comparable HIV− individuals, all former plasma donors, who lived in a rural part of China, received comprehensive medical and neuropsychological (NP) examinations. At study entry 56% of HIV+ group was on combination antiretroviral treatment (cART) and 60.9% at followup. Multiple regression change score approach was used with the HIV− sample to develop norms for change that would be then applied to the HIV+ participants. Followup test scores adjusted for the control group practice effect.
53 HIV+ individuals (27%) developed significant cognitive decline as compared to five (5%) of HIV− individuals. Cognitive decline was predicted at baseline by AIDS status, lower nadir CD4, and worse processing speed; at follow-up, it was associated with lower current CD4 and failure of viral suppression on cART. NP decline also was associated with decreased independence in activities of daily living. Using NP-impairment scores that were corrected for “practice” on repeated testing, we found that among the decliners, 41.5% (N=22) had incident impairment, while 38% (N=20) declined within the impaired range and another 20.7% (N=11) declined within the normal range.
This study demonstrates that despite ongoing cART, cognitive decline in HIV+ people is common over a one year follow-up. Regression-based norms for change on Western NP tests can be used to detect disease-related cognitive decline in a developing country.
HIV/AIDS; Neurocognitive Disorders; Incidence Studies; China; Longitudinal Studies; Neuropsychological Tests; Antiretroviral Therapy; Highly Active
When antiretroviral therapy does not fully suppress HIV replication, suboptimal levels of antiretrovirals can select for antiretroviral resistant variants of HIV. These variants may exhibit reduced replication capacity and result in lower viral loads in blood. Our study evaluated whether antiretroviral resistance was associated with viral loads in the cerebrospinal fluid (CSF) and better neuropsychological (NP) performance.
We enrolled ninety-four participants and each participant underwent a comprehensive neuromedical evaluation that used structured clinical assessments of medical history, ART and other medication use, comprehensive NP testing and neurological and general physical signs of disease. Blood was collected by venipuncture and all participants were offered lumbar puncture. Univariate and multivariate statistical methods were used to analyze the relationship between antiretroviral resistance, blood and CSF HIV RNA levels, substance use, and NP performance.
Antiretroviral resistance, detected in blood, was associated with lower CSF viral loads (p<0.01) and better NP performance (p=0.04) in multivariate analyses, independent of past and current ARV use and blood viral loads (Model: p< 0.01). However, HIV RNA levels in CSF did not independently correlate with NP performance. Low viral loads in the CSF limited our ability to investigate the relationship between antiretroviral resistance detected in CSF and NP performance.
Even in the absence of ART, antiretroviral resistance-associated mutations correlate with better NP performance possibly because these mutations reflect reduced neurovirulence compared with wild-type HIV.
Methamphetamine (meth) abuse is increasingly of public health concern and has been associated with neurocognitive dysfunction. Some previous studies have been hampered by background differences between meth users and comparison subjects, as well as unknown HIV and hepatitis C (HCV) status, which can also affect brain functioning. We compared the neurocognitive functioning of 54 meth dependent (METH+) study participants who had been abstinent for an average of 129 days, to that of 46 demographically comparable control subjects (METH-) with similar level of education and reading ability. All participants were free of HIV and HCV infection. The METH+ group exhibited higher rates of neuropsychological impairment in most areas tested. Among meth users, neuropsychologically normal (n=32) and impaired (n=22) subjects did not differ with respect to self-reported age at first use, total years of use, route of consumption, or length of abstinence. Those with motor impairment had significantly greater meth use in the past year, but impairment in cognitive domains was unrelated to meth exposure. The apparent lack of correspondence between substance use parameters and cognitive impairment suggests the need for further study of individual differences in vulnerability to the neurotoxic effects of methamphetamine.
Methamphetamine; Stimulant; Motor impairment; Neuropsychological; Cognitive impairment; Drug exposure; Predictors
Understanding the trajectory of cognitive changes in the development of schizophrenia may shed light on the neurodevelopmental processes in the beginning stage of illness. Subjects at risk for psychosis (AR, n=48), patients in their first episode of schizophrenia (FE, n=20) and normal comparison subjects (NC, n=29) were assessed on a neurocognitive battery at baseline and at a 6-month follow-up. There were significant group differences across all cognitive domains as well as a significant group by time interaction in the verbal learning domain. After statistically controlling for practice effects and regression to the mean, a high proportion of FE subjects showed an improvement in verbal learning, while a significant number of AR subjects improved in general intelligence. Moreover, a higher than expected percentage of FE subjects, as well as AR subjects who later converted to psychosis, showed a deterioration in working memory and processing speed. These inconsistent trajectories suggest that some domains may improve with stabilization in the early stages of psychosis, while others may decline with progression of the illness, indicating possible targets for cognitive remediation strategies and candidate vulnerability markers for future psychosis.
NEUROPSYCHOLOGICAL; LONGITUDINAL; SCHIZOPHRENIA; AT RISK; PRODROMAL
Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.
HIV; Combination antiretroviral therapy; HIV dementia
We examined neurocognitive functioning among persons with acute or early HIV infection (AEH) and hypothesized that the neurocognitive performance of AEH individuals would be intermediate between HIV seronegatives (HIV−) and those with chronic HIV infection. Comprehensive neurocognitive testing was accomplished with 39 AEH, 63 chronically HIV infected, and 38 HIV− participants. All AEH participants were HIV infected for less than 1 year. Average domain deficit scores were calculated in seven neurocognitive domains. HIV−, AEH, and chronically HIV infected groups were ranked from best (rank of 1) to worst (rank of 3) in each domain. All participants received detailed substance use, neuromedical, and psychiatric evaluations and HIV infected persons provided information on antiretroviral treatment and completed laboratory evaluations including plasma and CSF viral loads. A nonparametric test of ordered alternatives (Page test), and the appropriate nonparametric follow-up test, was used to evaluate level of neuropsychological (NP) functioning across and between groups. The median duration of infection for the AEH group was 16 weeks [interquartile range, IQR: 10.3–40.7] as compared to 4.9 years [2.8–11.1] in the chronic HIV group. A Page test using ranks of average scores in the seven neurocognitive domains showed a significant monotonic trend with the best neurocognitive functioning in the HIV− group (mean rank = 1.43), intermediate neurocognitive functioning in the AEH group (mean rank = 1.71), and the worst in the chronically HIV infected (mean rank = 2.86; L statistic = 94, p < 0.01); however, post-hoc testing comparing neurocognitive impairment of each group against each of the other groups showed that the chronically infected group was significantly different from both the HIV− and AEH groups on neurocognitive performance; the AEH group was statistically indistinguishable from the HIV− group. Regression models among HIV infected participants were unable to identify significant predictors of neurocognitive performance. Neurocognitive functioning was worst among persons with chronic HIV infection. Although a significant monotonic trend existed and patterns of the data suggest the AEH individuals may fall intermediate to HIV− and chronic participants, we were not able to statistically confirm this hypothesis.
HIV infection; HIV-associated neurocognitive disorders; Acute or early HIV; Primary HIV
Background: Mounting evidence suggests that compromised neurocognitive function is a central feature of schizophrenia. There are, however, schizophrenia patients with a normal neuropsychological (NP) performance, but estimates of the proportion of NP normal patients vary considerably between studies. Neurocognitive dysfunction is also a characteristic of other psychotic disorders, yet there are inconsistencies in the literature regarding the similarity to impairments in schizophrenia. NP normality in psychotic affective disorders has not been systematically studied.
Methods: Data came from the Suffolk County Mental Health Project, an epidemiological study of first-admission patients with psychotic disorders. Respondents with a diagnosis of schizophrenia (N = 94) or schizoaffective disorder (N = 15), bipolar disorder (N = 78), and major depressive disorder (N = 48) were administered a battery of NP tests assessing 8 cognitive domains 2 years after index admission. Patients’ performance profile was compared, and their NP status was classified based on 3 previously published criteria that vary in their stringency.
Results: The 4 diagnostic groups had comparable NP performance profile patterns. All groups demonstrated impairments in memory, executive functions, and attention and processing speed. However, schizophrenia patients were more impaired than the other groups on all cognitive domains. Results were not attenuated when IQ was controlled. Prevalence of NP normality ranged between 16% and 45% in schizophrenia, 20% and 33% in schizoaffective disorder, 42% and 64% in bipolar disorder, and 42% and 77% in depression, depending on the criterion employed.
Conclusions: Evidence suggests that differences in NP performance between schizophrenia and psychotic affective disorders are largely quantitative. NP impairment is also common in psychotic affective disorders. A significant minority of schizophrenia patients are NP normal.
normality; mood disorders; psychosis; cognition; intelligence