Article

Screening for Cognitive Impairment in Human Immunodeficiency Virus

Memory and Aging Center, Department of Neurology, University of California–San Francisco, USA.
Clinical Infectious Diseases (Impact Factor: 9.42). 10/2011; 53(8):836-42. DOI: 10.1093/cid/cir524
Source: PubMed

ABSTRACT Recent publications estimate the prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) exceeds 50%, and this rate is likely higher among older patients. Cognitive impairment may impact medication adherence, and symptomatic impairment has been linked to all-cause mortality providing some impetus for early detection. There are currently insufficient data to inform solid recommendations on screening methods. Most HIV-specific tools have poor performance characteristics for all but the most severe form of impairment, which accounts for <5% of cases. Reliance on symptoms is likely to miss a substantial proportion of individuals with HAND due to poor insight, confounding mood disturbances, and lack of well-informed proxies. In the aging HIV-positive population, broader screening tools may be required to allow sensitivity for both HIV and neurodegenerative disorders. We describe the clinical presentation of HAND, review existing data related to screening tools, and provide preliminary and practical recommendations in the absence of more definitive studies.

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    • "HIV-associated neurocognitive disorders (HAND) are a common complication of HIV infection in the era of combined antiretroviral therapy (cART) that independently predict overall morbidity and mortality (Ellis et al. 2007; Ellis et al. 1997; Valcour et al. 2011; Vivithanaporn et al. 2010). The clinical sub-syndromes of HAND vary in severity of cognitive impairment and associated functioning and include asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD) (Antinori et al. 2007). "
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    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; DOI:10.1007/s13365-015-0333-3 · 3.32 Impact Factor
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    • "Cognitive domains were classified as impaired when a score of less than −1.65 SD was obtained in more than half of the tasks in that domain. Test scores were classified as impaired when a score of less than −1.65 SD was obtained on the age-and education-adjusted score using the HDS to detect mild impairment in HIV-infected patients (Valcour et al. 2011; Bottigi et al. 2007; Zipursky et al. 2013). This screening tool was originally developed to detect HIV-associated dementia, and the performance characteristics to detect severe forms of cognitive impairment are modest to good (Berghuis et al. 1999). "
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    ABSTRACT: The gold standard for evaluating cognitive impairments in HIV-infected patients is to administer an extensive neuropsychological assessment. This may, however, be time-consuming and hence not always feasible in the clinic. Therefore, several brief screening tools have been developed. This study determined the validity of the Montreal Cognitive Assessment (MoCA) and the HIV Dementia Scale (HDS) in detecting cognitive impairment using both the Frascati and cognitive impairment, no dementia (CIND) criteria to classify cognitive impairment in HIV-1 infected patients. The MoCA, HDS, and an extensive neuropsychological assessment, covering nine cognitive domains, were administered in a group of 102 HIV-infected patients who were all on cART and virologically suppressed for at least 1 year. Results show that the areas under the curve (AUCs) for both the MoCA and the HDS were statistically significant, using both the Frascati and the CIND criteria as gold standard. However, the AUCs for the MoCA and HDS did not differ significantly, regardless of the used classification criteria (Frascati: z = 0.37, p = 0.35; CIND: z = -0.62, p = 0.27). Sensitivity of both the MoCA and HDS were low for the recommended cutoff scores (Frascati: MoCA (<26) = 0.56, HDS (<11) = 0.26; CIND: MoCA (<26) = 0.55, HDS (<11) = 0.36). Cutoff scores with good sensitivity and adequate specificity could not be determined for both screening instruments. Therefore, the HDS and MoCA are not recommended as sole instruments to diagnose HIV-associated cognitive impairment.
    Journal of NeuroVirology 02/2015; DOI:10.1007/s13365-015-0324-4 · 3.32 Impact Factor
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    • "Several publications report older age (Valcour et al. 2011) and low CD4 T lymphocyte nadir (Munoz-Moreno et al. 2008; Heaton et al. 2011) as predictors for NCI. The lack of correlation of these variables with NCI in our report may be due to limitations in sample size and few older patients. "
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    ABSTRACT: We compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks 0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV-negative Thais. We defined NCI as performance of <-1 SD on ≥2 tests. The Thai depression inventory was used to capture depressive symptoms. Lumbar puncture was optional at week 0 and 48. At baseline, median (IQR) age was 36.9 (32.8-40.5) years, and 46 % had primary school education or lower. The median CD4 count was 196 (107-292) cells/mm(3), and plasma HIV RNA was 4.1 (3.6-4.5) log(10) copies/ml. Almost all (97 %) had circulating recombinant CRF01_AE. At baseline, 20 (47 %) of the mLPV/r vs. 22 (44 %) of TDF/3TC/LPV/r arms met NCI criteria (p = 0.89). The frequency of NCI at week 48 was 30 vs. 32 % (p = 0.85) with 6 vs. 7 % (p = 0.85) developing NCI in the mLPV/r vs. TDF/3TC/LPV/r arms, respectively. Having NCI at baseline and lower education each predicted NCI at week 48. Depression scores at week 48 did not differ between arms (p = 0.47). Cerebrospinal fluid HIV RNA of <50 copies/ml at 48 weeks was observed in five out of seven in mLPV/r vs. three out of four in TDF/3TC/LPV/r arm. The rates of NCI and depression did not differ among cases failing NNRTI-based cART who received mLPV/r compared to LPV/r triple therapy.
    Journal of NeuroVirology 09/2012; DOI:10.1007/s13365-012-0127-9 · 3.32 Impact Factor
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