Carey CL, Woods SP, Gonzalez R, Conover E, Marcotte TD, Grant I et al, HNRC Group. Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J Clin Exp Neuropsychol 26: 307-319
ABSTRACT The current study explored the predictive validity of the Global Deficit Score (GDS) approach in summarizing neuropsychological (NP) test results, and specifically in detecting HIV-associated cognitive impairment. A comprehensive NP test battery was administered to 88 HIV+ subjects and 61 healthy HIV- controls comparable for age, education, and ethnicity. Demographically corrected test data were converted to a GDS, which simulates clinicians' ratings by quantifying the number and degree of impaired performances throughout the test battery while attaching relatively less significance to superior performances and/or those within normal limits. Our results indicated that the GDS approach effectively discriminated HIV+ and normal control groups, and accurately classified HIV+ individuals with NP impairment based on the "gold standard" clinical rating approach. Consistent with previous studies using different subject samples and different NP test batteries, the GDS cutpoint of >or=0.50 yielded optimal balance between sensitivity and specificity in classifying NP impairment, thus supporting the generalizability of the method. Moreover, the ability of the GDS to predict NP impairment across several cutpoints was quite strong, with positive predictive power values ranging from 0.71 to 1.00. These findings support the validity of the GDS as a clinically useful way of summarizing results on NP testing.
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- "). A global performance score was determined as previously described (Carey et al. 2004; Woods et al. 2004). HAND status was classified according to Frascati criteria (Antinori et al. 2007). "
ABSTRACT: HIV-associated neurocognitive disorders (HAND) affect up to 50 % of HIV-infected adults, independently predict HIV morbidity/mortality, and are associated with neuronal damage and monocyte activation. Cerebrospinal fluid (CSF) neurofilament subunits (NFL, pNFH) are sensitive surrogate markers of neuronal damage in several neurodegenerative diseases. In HIV, CSF NFL is elevated in individuals with and without cognitive impairment, suggesting early/persistent neuronal injury during HIV infection. Although individuals with severe cognitive impairment (HIV-associated dementia (HAD)) express higher CSF NFL levels than cognitively normal HIV-infected individuals, the relationships between severity of cognitive impairment, monocyte activation, neurofilament expression, and systemic infection are unclear. We performed a retrospective cross-sectional study of 48 HIV-infected adults with varying levels of cognitive impairment, not receiving antiretroviral therapy (ART), enrolled in the CNS Anti-Retroviral Therapy Effects Research (CHARTER) study. We quantified NFL, pNFH, and monocyte activation markers (sCD14/sCD163) in paired CSF/plasma samples. By examining subjects off ART, these correlations are not confounded by possible effects of ART on inflammation and neurodegeneration. We found that CSF NFL levels were elevated in individuals with HAD compared to cognitively normal or mildly impaired individuals with CD4+ T-lymphocyte nadirs ≤200. In addition, CSF NFL levels were significantly positively correlated to plasma HIV-1 RNA viral load and negatively correlated to plasma CD4+ T-lymphocyte count, suggesting a link between neuronal injury and systemic HIV infection. Finally, CSF NFL was significantly positively correlated with CSF pNFH, sCD163, and sCD14, demonstrating that monocyte activation within the CNS compartment is directly associated with neuronal injury at all stages of HAND.Journal of NeuroVirology 03/2015; 21(4). DOI:10.1007/s13365-015-0333-3 · 2.60 Impact Factor
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- "The domain-specific Z scores were then averaged and independent samples t test was used to examine if mean group differences exist. In order to estimate impairment rates, we utilized a global deficit-type approach (Carey et al. 2004) by assigning a score from 0 to 5 based on number of Z score standard deviations from normal. Worse cognitive performance results in a higher Z score deficit score "
ABSTRACT: The Romanian cohort can provide valuable information about the effect of chronic HIV-infection and exposure to combined antiretroviral therapy (cART) on the developing brain, based on its unique characteristics: young adults infected parenterally with HIV clade F in the late 1980s and exposed to cART for a decade. We conducted a prospective study using a neuropsychological test battery validated in other international HIV cohorts, in order to evaluate the rate and severity of neurocognitive impairment in a group of young Romanian adults. The 49 HIV-infected (HIV+) participants and the 20 HIV negative (HIV-) controls were similar for age and gender, although the HIV- group tended to be more educated. We found higher cognitive impairment prevalence in the HIV+ group (59.1 %) versus the HIV- group (10 %), and the impairment rate remained significantly higher even when the groups were matched based on the educational level (38.7 % for the HIV+ group vs. 10.0 % for the HIV- controls; p = 0.025). The nadir CD4 count was <200 in 71.4 % of patients, but at the time of neurocognitive assessment, 89.5 % of patients had normal immunological status and 81.8 % undetectable HIV load. Among the HIV-impaired group, 26 % of the participants had syndromic impairment while the other 74 % had asymptomatic neurocognitive impairment. We found a high prevalence of neurocognitive dysfunction in the Romanian young adults growing-up with HIV. The greatest HIV-related cognitive deficits were in the domains of executive and motor functioning, consistent with a frontosubcortical pattern.Journal of NeuroVirology 09/2014; 20(5). DOI:10.1007/s13365-014-0275-1 · 2.60 Impact Factor
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- "A patient was then classified as having MND if they complained of symptoms thought to be related to neurocognitive impairment and as having HAD if they had a Karnofsky performance score of less than 80% due to neurocognitive symptoms. To provide a continuous measurement of purely neurocognitive performance, a global deficit score (GDS)  was calculated by finding the average of all the z scores for each of 13 neurocognitive tests. "
ABSTRACT: Background Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART. Methods HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery. Results One hundred and six HIV positive patients, with median (range) age 39 (18–71) years, 73% female and median (range) CD4 count 323.5 (68–1039) cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV associated dementia [HAD]). A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI); however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD) nor asymptomatic (ANI) forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p = 0.696) and aOR 0.577 (CI. 0.09, 3.605; p = 0.556) respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition. Discussion/Conclusion Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and determination of the clinical relevance of ANI.PLoS ONE 06/2014; 9(6):e98962. DOI:10.1371/journal.pone.0098962 · 3.23 Impact Factor