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: 8.89). 10/2011; 53(8):836-42. DOI: 10.1093/cid/cir524
Source: PubMed


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.

1 Follower
7 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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; 21(4). DOI:10.1007/s13365-015-0324-4 · 2.60 Impact Factor
  • Source
    • "Valcour and colleagues [17••] recently summarised existing HAND screens, however their review was not exhaustive and did not differentiate between those validated in pre-cART versus cART samples or against a gold standard neuropsychological assessment. More recently, a systematic review [18••] was conducted, although it was limited to the screening accuracy of the HDS and International HDS, and calculation excluded those with ANI, the most common form of HAND. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Various screening tools have been proposed to identify HIV-Associated Neurocognitive Disorder (HAND). However, there has been no systematic review of their strengths and weaknesses in detecting HAND when compared to gold standard neuropsychological testing. Thirty-five studies assessing HAND screens that were conducted in the era of combination antiretroviral therapy were retrieved using standard search procedures. Of those, 19 (54 %) compared their screen to standard neuropsychological testing. Studies were characterised by a wide variation in criterion validity primarily due to non-standard definition of neurocognitive impairment, and to the demographic and clinical heterogeneity of samples. Assessment of construct validity was lacking, and longitudinal useability was not established. To address these limitations, the current review proposed a summary of the most sensitive and specific studies (>70 %), as well as providing explicit caution regarding their weaknesses, and recommendations for their use in HIV primary care settings. Electronic supplementary material The online version of this article (doi:10.1007/s11904-013-0176-6) contains supplementary material, which is available to authorized users.
    Current HIV/AIDS Reports 09/2013; 10(4). DOI:10.1007/s11904-013-0176-6 · 3.80 Impact Factor
Show more

Preview (2 Sources)

7 Reads
Available from