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Impaired Neurocognitive Performance and Mortality in HIV: Assessing the Prognostic Value of the HIV-Dementia Scale

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Abstract

This study examined whether global HIV-associated neurocognitive impairment (NCI), assessed with the HIV-Dementia Scale (HDS), predicted mortality in an ethnically diverse sample of 209 HIV-positive adults. Participants were predominantly in the mid-range of illness at baseline, and followed over 13-years. At baseline, 31 (15%) participants scored in the NCI range (HDS ≤ 10); 58 (28%) died during follow-up. Baseline NCI was significantly associated with earlier mortality (HR = 2.10, 95% CI [1.10–4.00]) independent of sociodemographic and HIV disease-related covariates. Less errors on the antisaccade task, an index of executive/attention control, was the only HDS subtest predicting earlier mortality (HR = 0.72, 95% CI [0.58–0.90]). In the absence of an AIDS-defining condition, NCI, particularly in the executive/attention domain, is an independent prognostic marker of mortality in a diverse HIV-positive cohort. These findings highlight the clinical utility of brief cognitive screening measures in this population.

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References

  1. Sacktor N, Skolasky RL, Seaberg E, Munro C, Becker JT, Martin E, et al. Prevalence of HIV-associated neurocognitive disorders in the multicenter AIDS cohort study. Neurology. 2016;86(4):334–40.

    CAS  Google Scholar 

  2. Cysique LA, Brew BJ. Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev. 2009;19(2):169–85.

    PubMed  Google Scholar 

  3. Heaton R, Franklin D, Ellis R, McCutchan J, Letendre S, LeBlanc S, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011;17(1):3–16.

    CAS  PubMed  Google Scholar 

  4. Reger M, Welsh R, Razani J, Martin DJ, Boone KB. A meta-analysis of the neuropsychological sequelae of HIV infection. J Int Neuropsychol Soc. 2002;8(03):410–24.

    PubMed  Google Scholar 

  5. Woods SP, Moore DJ, Weber E, Grant I. Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev. 2009;19(2):152–68.

    PubMed  PubMed Central  Google Scholar 

  6. Heaton RK, Marcotte TD, Mindt MR, Sadek J, Moore DJ, Bentley H, et al. The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsychol Soc. 2004;10(3):317–31.

    PubMed  Google Scholar 

  7. Marcotte TD, Heaton RK, Wolfson T, Taylor MJ, Alhassoon O, Arfaa K, et al. The impact of HIV-related neuropsychological dysfunction on driving behavior The HNRC Group. J Int Neuropsychol Soc. 1999;5(7):579–92.

    CAS  PubMed  Google Scholar 

  8. Albright AV, Soldan SS, González-Scarano F. Pathogenesis of human immunodeficiency virus-induced neurological disease. J Neurovirol. 2003;9(2):222–7.

    CAS  PubMed  Google Scholar 

  9. Hult B, Chana G, Masliah E, Everall I. Neurobiology of HIV. Int Rev Psychiatry. 2008;20(1):3–13.

    PubMed  Google Scholar 

  10. Mocchetti I, Bachis A, Avdoshina V. Neurotoxicity of human immunodeficiency virus-1: viral proteins and axonal transport. Neurotox Res. 2012;21(1):79–89.

    CAS  PubMed  Google Scholar 

  11. Iskander S, Walsh KA, Hammond RR. Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia. J Neuroinflamm. 2004;1(1):1.

    Google Scholar 

  12. Kaul M. HIV-1 associated dementia: update on pathological mechanisms and therapeutic approaches. Curr Opin Neurol. 2009;22(3):315.

    PubMed  PubMed Central  Google Scholar 

  13. Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, et al. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol. 2008;65(1):65–70.

    PubMed  PubMed Central  Google Scholar 

  14. Ellis RJ, Calero P, Stockin MD. HIV infection and the central nervous system: a primer. Neuropsychol Rev. 2009;19(2):144–51.

    PubMed  PubMed Central  Google Scholar 

  15. Brew BJ. Has HIV-associated neurocognitive disorders now transformed into vascular cognitive impairment? AIDS. 2016;30(15):2379–80.

    PubMed  Google Scholar 

  16. Crum NF, Riffenburgh RH, Wegner S, Agan BK, Tasker SA, Spooner KM, et al. Comparisons of causes of death and mortality rates among HIV-infected persons: analysis of the pre-, early, and late HAART (highly active antiretroviral therapy) eras. J Acquir Immune Defic Syndr. 2006;41(2):194–200.

    PubMed  Google Scholar 

  17. Murphy EL, Collier AC, Kalish LA, Assmann SF, Para MF, Flanigan TP, et al. Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Ann Intern Med. 2001;135(1):17–26.

    CAS  PubMed  Google Scholar 

  18. Bhaskaran K, Hamouda O, Sannes M, Boufassa F, Johnson AM, Lambert PC, et al. Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA. 2008;300(1):51–9.

    CAS  PubMed  Google Scholar 

  19. van Sighem A, Danner S, Ghani AC, Gras L, Anderson RM, de Wolf F. Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals. J Acquir Immune Defic Syndr. 2005;40(2):212–8.

    PubMed  Google Scholar 

  20. Lohse N, Hansen AB, Pedersen G, Kronborg G, Gerstoft J, Sorensen HT, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med. 2007;146(2):87–95.

    PubMed  Google Scholar 

  21. Trickey A, May MT, Vehreschild J-J, Obel N, Gill MJ, Crane HM, et al. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017;4(8):e349–56.

    Google Scholar 

  22. Blatt SP, McCarthy WF, Bucko-Krasnicka B, Melcher GP, Boswell RN, Dolan MJ, et al. Multivariate models for predicting progression to AIDS and survival in human immunodeficiency virus-infected persons. J Infect Dis. 1995;171(4):837–44.

    CAS  PubMed  Google Scholar 

  23. Luo K, Law M, Kaldor JM, McDonald AM, Cooper DA. The role of initial AIDS-defining illness in survival following AIDS. AIDS. 1995;9(1):57–64.

    CAS  PubMed  Google Scholar 

  24. Nightingale SD, Jockusch JD, Haslund I, Cal SX, Peterson DM, Loss SD. Logarithmic relationship of the CD4 count to survival in patients with human immunodeficiency virus infection. Arch Intern Med. 1993;153(11):1313–8.

    CAS  PubMed  Google Scholar 

  25. Ellis RJ, Deutsch R, Heaton RK, Marcotte TD, McCutchan JA, Nelson JA, et al. Neurocognitive impairment is an independent risk factor for death in HIV infection. Arch Neurol. 1997;54(4):416–24.

    CAS  PubMed  Google Scholar 

  26. Mayeux R, Stern Y, Tang M, Todak G, Marder K, Sano M, et al. Mortality risks in gay men with human immunodeficiency virus infection and cognitive impairment. Neurology. 1993;43(1 Part 1):176.

    CAS  PubMed  Google Scholar 

  27. McArthur JC, Hoover D, Bacellar H, Miller E, Cohen B, Becker J, et al. Dementia in AIDS patients incidence and risk factors. Neurology. 1993;43(11):2245.

    CAS  PubMed  Google Scholar 

  28. Sevigny JJ, Albert SM, McDermott MP, Schifitto G, McArthur JC, Sacktor N, et al. An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection. Arch Neurol. 2007;64(1):97–102.

    PubMed  Google Scholar 

  29. Vivithanaporn P, Heo G, Gamble J, Krentz HB, Hoke A, Gill MJ, et al. Neurologic disease burden in treated HIV/AIDS predicts survival: a population-based study. Neurology. 2010;75(13):1150–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Wilkie FL, Goodkin K, Eisdorfer C, Feaster D, Morgan R, Fletcher MA, et al. Mild cognitive impairment and risk of mortality in HIV-1 infection. J Neuropsychiatry Clin Neurosci. 1998;10(2):125–32.

    CAS  PubMed  Google Scholar 

  31. Spitzer RL, First MB, Gibbon M, Williams JB. Structured clinical interview for DSM-III-R. Washington, DC: American Psychiatric Press; 1990.

    Google Scholar 

  32. Power C, Selnes OA, Grim JA, McArthur JC. HIV Dementia Scale: a rapid screening test. J Acquir Immune Defic Syndr. 1995;8(3):273–8.

    CAS  Google Scholar 

  33. Hutton SB. Cognitive control of saccadic eye movements. Brain Cogn. 2008;68(3):327–40.

    CAS  PubMed  Google Scholar 

  34. Ganasen K, Fincham D, Smit J, Seedat S, Stein D. Utility of the HIV Dementia Scale (HDS) in identifying HIV dementia in a South African sample. J Neurol Sci. 2008;269(1):62–4.

    CAS  PubMed  Google Scholar 

  35. Bottiggi KA, Chang JJ, Schmitt FA, Avison MJ, Mootoor Y, Nath A, et al. The HIV Dementia Scale: predictive power in mild dementia and HAART. J Neurol Sci. 2007;260(1):11–5.

    PubMed  Google Scholar 

  36. Hu X, Zhou Y, Long J, Feng Q, Wang R, Su L, et al. Diagnostic accuracy of the International HIV Dementia Scale and HIV Dementia Scale: a meta-analysis. Exp Ther Med. 2012;4(4):665–8.

    PubMed  PubMed Central  Google Scholar 

  37. Joska JA, Fincham DS, Stein DJ, Paul RH, Seedat S. Clinical correlates of HIV-associated neurocognitive disorders in South Africa. AIDS Behav. 2010;14(2):371–8.

    PubMed  Google Scholar 

  38. Beck AT, Steer RA, Brown GK. Beck depression inventory-II. San Antonio. 1996;78(2):490–8.

    Google Scholar 

  39. Tozzi V, Balestra P, Serraino D, Bellagamba R, Corpolongo A, Piselli P, et al. Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART. AIDS Res Hum Retroviruses. 2005;21(8):706–13.

    PubMed  Google Scholar 

  40. Hinkin C, Castellon S, Durvasula R, Hardy D, Lam M, Mason K, et al. Medication adherence among HIV + adults effects of cognitive dysfunction and regimen complexity. Neurology. 2002;59(12):1944–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Lima VD, Harrigan R, Bangsberg DR, Hogg RS, Gross R, Yip B, et al. The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time. J Acquir Immune Defic Syndr. 2009;50(5):529.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Okonkwo O, Vance D, Antia L, Smith B, Blanshan S, Heirs K, et al. Service utilization and cognitive complaints in adults with HIV: results from a statewide survey. J HIV/AIDS Soc Serv. 2008;7(2):175–94.

    Google Scholar 

  43. Peluso MJ, Ferretti F, Peterson J, Lee E, Fuchs D, Boschini A, et al. Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well-controlled plasma viral load. AIDS. 2012;26(14):1765–74.

    CAS  PubMed  Google Scholar 

  44. Perk J, De Backer G, Gohlke H, Graham I, Reiner Ž, Verschuren M, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33(13):1635–701.

    CAS  PubMed  Google Scholar 

  45. Currier JS, Lundgren JD, Carr A, Klein D, Sabin CA, Sax PE, et al. Epidemiological evidence for cardiovascular disease in HIV-infected patients and relationship to highly active antiretroviral therapy. Circulation. 2008;118(2):e29–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Cruse B, Cysique LA, Markus R, Brew BJ. Cerebrovascular disease in HIV-infected individuals in the era of highly active antiretroviral therapy. J Neurovirol. 2012;18(4):264–76.

    CAS  PubMed  Google Scholar 

  47. Mateen FJ, Post WS, Sacktor N, Abraham AG, Becker JT, Smith BR, et al. Long-term predictive value of the Framingham Risk Score for Stroke in HIV-positive vs HIV-negative men. Neurology. 2013;81(24):2094–102.

    PubMed  PubMed Central  Google Scholar 

  48. Vinikoor MJ, Napravnik S, Floris-Moore M, Wilson S, Huang DY, Eron JJ. Incidence and clinical features of cerebrovascular disease among HIV-infected adults in the Southeastern United States. AIDS Res Hum Retroviruses. 2013;29(7):1068–74.

    PubMed  PubMed Central  Google Scholar 

  49. Benjamin LA, Bryer A, Emsley HC, Khoo S, Solomon T, Connor MD. HIV infection and stroke: current perspectives and future directions. Lancet Neurol. 2012;11(10):878–90.

    PubMed  PubMed Central  Google Scholar 

  50. Wang T, Yi R, Green LA, Chelvanambi S, Seimetz M, Clauss M. Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat. Cardiovasc Pathol. 2015;24(5):279–82.

    PubMed  PubMed Central  Google Scholar 

  51. Su T, Wit FW, Caan MW, Schouten J, Prins M, Geurtsen GJ, et al. White matter hyperintensities in relation to cognition in HIV-infected men with sustained suppressed viral load on combination antiretroviral therapy. AIDS. 2016;30(15):2329–39.

    CAS  PubMed  Google Scholar 

  52. Wright E, Grund B, Robertson K, Brew B, Roediger M, Bain M, et al. Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons. Neurology. 2010;75(10):864–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Sacktor N, Bacellar H, Hoover D, Nance-Sproson T, Seines O, Miller E, et al. Psychomotor slowing in HIV infection: a predictor of dementia, AIDS and death. J Neurovirol. 1996;2(6):404–10.

    CAS  PubMed  Google Scholar 

  54. Massen C. Parallel programming of exogenous and endogenous components in the antisaccade task. Q J Exp Psychol Sect A. 2004;57(3):475–98.

    Google Scholar 

  55. Ettinger U, Ffytche DH, Kumari V, Kathmann N, Reuter B, Zelaya F, et al. Decomposing the neural correlates of antisaccade eye movements using event-related FMRI. Cereb Cortex. 2007;18(5):1148–59.

    PubMed  Google Scholar 

  56. Matsuda T, Matsuura M, Ohkubo T, Ohkubo H, Matsushima E, Inoue K, et al. Functional MRI mapping of brain activation during visually guided saccades and antisaccades: cortical and subcortical networks. Psychiatry Res. 2004;131(2):147–55.

    PubMed  Google Scholar 

  57. Niendam TA, Laird AR, Ray KL, Dean YM, Glahn DC, Carter CS. Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cogn Affect Behav Neurosci. 2012;12(2):241–68.

    PubMed  PubMed Central  Google Scholar 

  58. Hutton SB, Ettinger U. The antisaccade task as a research tool in psychopathology: a critical review. Psychophysiology. 2006;43(3):302–13.

    PubMed  Google Scholar 

  59. Castello E, Baroni N, Pallestrini E. Neurotological and auditory brain stem response findings in human immunodeficiency virus—positive patients without neurologic manifestations. Ann Otol Rhinol Laryngol. 1998;107(12):1054–60.

    CAS  PubMed  Google Scholar 

  60. Archibald SL, Masliah E, Fennema-Notestine C, Marcotte TD, Ellis RJ, McCutchan JA, et al. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss. Arch Neurol. 2004;61(3):369–76.

    PubMed  Google Scholar 

  61. Castelo JMB, Sherman SJ, Courtney MG, Melrose RJ, Stern CE. Altered hippocampal-prefrontal activation in HIV patients during episodic memory encoding. Neurology. 2006;66(11):1688–95.

    CAS  PubMed  Google Scholar 

  62. Pfefferbaum A, Rosenbloom MJ, Rohlfing T, Kemper CA, Deresinski S, Sullivan EV. Frontostriatal fiber bundle compromise in HIV infection without dementia. AIDS. 2009;23(15):1977.

    PubMed  PubMed Central  Google Scholar 

  63. Tarwater PM, Gallant JE, Mellors JW, Gore ME, Phair JP, Detels R, et al. Prognostic value of plasma HIV RNA among highly active antiretroviral therapy users. AIDS. 2004;18(18):2419–23.

    PubMed  Google Scholar 

  64. Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, Musisi S, et al. The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS. 2005;19(13):1367–74.

    PubMed  Google Scholar 

  65. Haddow LJ, Floyd S, Copas A, Gilson RJC. A systematic review of the screening accuracy of the HIV Dementia Scale and International HIV Dementia Scale. PLoS ONE. 2013;8(4):e61826.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Valcour V, Paul R, Chiao S, Wendelken LA, Miller B. Screening for cognitive impairment in human immunodeficiency virus. Clin Infect Dis. 2011;53(8):836–42.

    PubMed  PubMed Central  Google Scholar 

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Funding

This research was graciously supported by the National Institute of Mental Health (R01MH53791 and R01MH066697, PI: Dr. Ironson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Psychology, University of Miami, 5665 Ponce de Leon Blvd., Coral Gables, FL, 33124-0751, USA

    Nikhil Banerjee, Roger C. McIntosh & Gail Ironson

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  1. Nikhil Banerjee
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Correspondence to Nikhil Banerjee.

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Ethical approval for this study was obtained from the University of Miami’s Institutional Review Board. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or National Research Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Banerjee, N., McIntosh, R.C. & Ironson, G. Impaired Neurocognitive Performance and Mortality in HIV: Assessing the Prognostic Value of the HIV-Dementia Scale. AIDS Behav 23, 3482–3492 (2019). https://doi.org/10.1007/s10461-019-02423-w

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