Biomedical subjects

Mariana Cherner

Publications and source records attributed to Mariana Cherner.

9 recordsLinked to original sources

PubMed2006

Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment.

OBJECTIVE: To determine the association of markers of regional neurodegeneration (ND) at autopsy to degree of neurocognitive impairment in persons with HIV. DESIGN: In a prospectively followed cohort of HIV-infected individuals we examined the relationship between antemortem neuropsychological (NP) abilities and postmortem neuropathological data. METHODS: Twenty-seven HIV-infected individuals with both neuropsychological and neuropathological data were identified. Laser confocal scanning microscopy was used to determine the degree of ND based on: (1) microtubule-associated protein (MAP2; reflecting neuronal cell bodies and dendrites) and (2) synaptophysin (SYN; a measure of presynaptic terminals). A regional combined score, based on the distribution of percentage neuropil occupied by MAP2 and SYN and emphasizing severity of ND, was created for each brain region: midfrontal cortex, hippocampus, and putamen. RESULTS: The regional combined scores from each brain region studied were better correlated with level of global NP impairment than measures of SYN and MAP2 individually. In a regression, hippocampal and putamen regional combined scores were independent predictors of degree of antemortem NP impairment (F(3,23) = 6.17; P < 0.01; R2 = 0.45). The correlations among regional ND measures demonstrated that ND is unevenly distributed across multiple brain regions. CONCLUSIONS: As the anatomic distribution and temporal progression of neuropathologic changes appears to differ across individuals, it is important to consider both cortical and subcortical brain regions in studies of neuropathogenesis and treatment of HIV-related brain disease. Furthermore, combining information from several markers of neural injury provided the strongest association with degree of neurocognitive impairment during life.

Adult↗

PubMed2005

Deficient strategic control of verbal encoding and retrieval in individuals with methamphetamine dependence.

Methamphetamine (MA) dependence is associated with deficits in episodic verbal memory, but the cognitive mechanisms underlying such impairments are not known. The authors evaluated a component process model of episodic verbal memory in 87 persons with MA dependence (MA+) and 71 demographically similar non-MA-using controls (MA-). Compared with MA- controls, MA+ participants demonstrated deficient overall learning, free recall, and utilization of semantic clustering, as well as higher rates of repetitions and intrusions. No between-groups differences were evident on measures of serial clustering, retention, or recognition discrimination. Taken together, these findings indicate that MA dependence is associated with deficient strategic (i.e., executive) control of verbal encoding and retrieval, which is consistent with the sequelae of MA-related prefronto-striatal circuit neurotoxicity.

Adult↗

PubMed2005

The effects of hepatitis C, HIV, and methamphetamine dependence on neuropsychological performance: biological correlates of disease.

OBJECTIVE: To determine the effects of hepatitis C virus (HCV) infection on neuropsychological (NP) performance. DESIGN: Cross-sectional analysis of a prospectively enrolled cohort. METHODS: A total of 239 HIV-seropositive and 287 HIV-seronegative subjects enrolled in prospective cohort studies at a single center. Subjects underwent standardized assessments, including comprehensive neuropsychological testing, substance use inventory neuromedical examination, venipuncture, and lumbar puncture. HCV antibody was measured in serum. In seropositive individuals, HCV RNA was measured in plasma and cerebrospinal fluid (CSF). RESULTS: HCV-seropositive subjects performed worse on neuropsychological testing and were almost twice as likely to be diagnosed as globally impaired, compared with those who were HCV seronegative. In a multivariate analysis, HCV, HIV, and methamphetamine dependence were independently associated with worse performance, even after adjusting for Centers for Disease Control stage and antiretroviral use. HCV-RNA levels in plasma were higher in those with memory, but not global, impairment. In cerebrospinal fluid, HCV RNA was below 100 copies/ml in all specimens. In HIV-infected subjects, HCV was associated with higher levels of HIV RNA in CSF, but not in plasma. HCV was also associated with higher levels of monocyte chemotactic protein 1, TNF-alpha, and soluble TNF receptor II. HCV-seropositive subjects did not appear to have advanced liver disease. CONCLUSIONS: HIV, HCV, and methamphetamine independently injure the central nervous system, leading to global neuropsychological impairment. HCV may injure the brain by viral or immune-mediated mechanisms. HCV-associated brain injury may be preventable or reversible because HCV infection is potentially curable.

Adult↗

PubMed2004

Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure.

Abuse of the stimulant drug methamphetamine is associated with neural injury and neuropsychological (NP) deficits, while the residual effects of marijuana use remain uncertain. We sought to determine if methamphetamine dependent persons who also met criteria for marijuana abuse or dependence evidenced different NP performance than those with dependence for methamphetamine alone. We examined three groups that did not differ significantly on important demographic factors: (1) subjects with a history of methamphetamine dependence and history of marijuana abuse/dependence (METH+/MJ+, n=27); (2) methamphetamine dependent subjects without history of marijuana abuse/dependence (METH+/MJ-, n=26); (3) a control group with minimal or no drug use (n=41). A comprehensive NP battery was administered and performance was quantified for five cognitive ability areas. The METH+/MJ- group generally demonstrated the greatest NP impairment, with statistically significant differences observed between the METH+/MJ- and control group in learning, retention/retrieval, and a summary score of global NP performance. The METH+/MJ+ group did not differ significantly from the control or METH+/MJ- group on any NP ability. However, there was a significant linear trend in the global NP score suggesting that the METH+/MJ+ performed intermediate to the control and METH+/MJ- groups. Based on these findings, we cannot conclude that there is a protective effect of marijuana use in methamphetamine users; however, marijuana use clearly did not appear to exacerbate methamphetamine neurotoxicity. Further investigations are needed to determine if the emerging literature, suggesting that certain cannabinoids might have neuroprotective actions, is generalizable to community-dwelling substance abusers.

Adult↗

PubMed2004

Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV.

We examined the interrater (IRR) of clinical ratings of neuropsychological (NP) impairment and neurocognitive diagnoses in HIV. Thirty participants with advanced HIV-infection who were enrolled in a multicenter HIV brain banking research project underwent comprehensive NP and neuromedical evaluations. Using a standardized system of guidelines, neuropsychologists from six participating sites independently assigned clinical ratings of NP impairment, as well as multilevel diagnoses reflecting the inferred etiology of the impairments and their effects on everyday functioning. Findings indicated excellent IRR in rating the presence and severity of NP impairment, but overall modest IRR for neurocognitive diagnoses. Not surprisingly, most diagnostic disagreements concerned the etiology of impairments in persons with medical and neuropsychiatric risk factors in addition to HIV.

Adult↗

PubMed2003

Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy.

Abuse of methamphetamine (METH) is a frequent comorbidity among individuals infected with human immunodeficiency virus (HIV) type 1. In cell cultures and animal models, METH accelerates retroviral replication. To determine whether METH increases HIV replication in humans, we evaluated HIV loads in HIV-positive METH users and nonusers. We studied 3 groups: Tox+, active METH use and positive urine toxicology results; METH(+)Tox-, previous METH dependence/abuse and negative urine toxicology results; METH(-)Tox-, no METH dependence/abuse and negative urine toxicology results. Tox+ subjects' plasma virus loads were significantly higher than METH(+)Tox- and METH(-)Tox- subjects'; cerebrospinal fluid virus loads showed a similar but nonsignificant trend. Stratification by use of highly active antiretroviral therapy (HAART) revealed that virus loads were higher only in those Tox+ subjects who reported receiving HAART. In contrast, abstinent former METH abusers (METH(+)Tox-) receiving HAART effectively suppressed viral replication. These data suggest that abstinence programs are a key component of effective treatment of HIV in METH-abusing populations.

Anti-HIV Agents↗

PubMed2003

Computerized reaction time battery versus a traditional neuropsychological battery: detecting HIV-related impairments.

In recent years, interest in the use of computerized neuropsychological (NP) assessment measures has increased. However, there are limited data regarding how performance on these measures relates to performance on more traditional, clinical instruments. In the present study, 82 HIV+ men, who were all believed on clinical grounds to have neurobehavioral impairment, completed a traditional NP battery (TNB) and the California Computerized Assessment Package (CalCAP, a collection of computerized reaction time tests). Summary scores based on a TNB, as well as those based on the CalCAP, demonstrated significant associations with both degree of immunosuppression (CD4 count) and detectable viral load in cerebrospinal fluid, but not with detectable viral load in plasma. Established norms on the TNB and CalCAP batteries resulted in classifying 57% and 49% of the HIV+ sample as impaired, respectively. When using the TNB as the "gold standard," impairment classifications based on CalCAP summary scores exhibited a sensitivity of 68% and a specificity of 77%. Overall agreement on impairment classifications between batteries was low (kappa = .44). Data from this study suggest that traditional NP batteries and computerized reaction time tests do not measure the same thing, and are not interchangeable in examining HIV-related NP impairments.

AIDS Dementia Complex↗

PubMed2003

The functional impact of HIV-associated neuropsychological impairment in Spanish-speaking adults: a pilot study.

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.

AIDS Dementia Complex↗

PubMed2003

The 50 and 100-item short forms of the Paced Auditory Serial Addition Task (PASAT): demographically corrected norms and comparisons with the full PASAT in normal and clinical samples.

While the standard 200-item version of the Paced Auditory Serial Addition Task (PASAT) is a sensitive neuropsychological instrument, it can be quite aversive to some patients due to its length and progressively increasing difficulty. We present demographically-corrected norms for 50 and 100-item short-form versions in a sample of 560 neurologically normal adults. Age, education, and ethnicity (but not gender) were found to be significant predictors of performance. In a clinical sample of 786 HIV-infected adults, diagnostic accuracy of the 50, 100, and 200-item versions was essentially equivalent (using clinical ratings of a comprehensive neuropsychological battery as the gold standard, overall classification rates of the three PASAT versions were 71%, 74%, and 73%, respectively), with better specificity (89-92%) than sensitivity (46-53%). The 50-item version showed moderate ceiling effects, but the 100-item test did not. In a mixed clinical sample of 40 subjects, the 50-item version was administered more than twice as fast as the 200-item version, and was tolerated better (discomfort rating of 4.0 vs. 5.9 on a 10-point scale, p < .05). We conclude that in many cases the PASAT-50 and PASAT-100 provide equivalent diagnostic accuracy with a significant reduction in administration time and patient discomfort.

Adult↗