AIDS and Behavior

, Volume 23, Issue 12, pp 3482–3492 | Cite as

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

  • Nikhil BanerjeeEmail author
  • Roger C. McIntosh
  • Gail Ironson
Original Paper


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.


HIV Neurocognitive impairment HIV-dementia scale Mortality Antisaccade 



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.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interests to disclose.

Ethical Approval

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.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. 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.Google Scholar
  2. 2.
    Cysique LA, Brew BJ. Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev. 2009;19(2):169–85.PubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 5.
    Woods SP, Moore DJ, Weber E, Grant I. Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev. 2009;19(2):152–68.PubMedPubMedCentralGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 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.PubMedGoogle Scholar
  8. 8.
    Albright AV, Soldan SS, González-Scarano F. Pathogenesis of human immunodeficiency virus-induced neurological disease. J Neurovirol. 2003;9(2):222–7.PubMedGoogle Scholar
  9. 9.
    Hult B, Chana G, Masliah E, Everall I. Neurobiology of HIV. Int Rev Psychiatry. 2008;20(1):3–13.PubMedGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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. 12.
    Kaul M. HIV-1 associated dementia: update on pathological mechanisms and therapeutic approaches. Curr Opin Neurol. 2009;22(3):315.PubMedPubMedCentralGoogle Scholar
  13. 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.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Ellis RJ, Calero P, Stockin MD. HIV infection and the central nervous system: a primer. Neuropsychol Rev. 2009;19(2):144–51.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Brew BJ. Has HIV-associated neurocognitive disorders now transformed into vascular cognitive impairment? AIDS. 2016;30(15):2379–80.PubMedGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.PubMedGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 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. 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.PubMedGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.PubMedGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. 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.PubMedGoogle Scholar
  29. 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.PubMedPubMedCentralGoogle Scholar
  30. 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.PubMedGoogle Scholar
  31. 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. 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.Google Scholar
  33. 33.
    Hutton SB. Cognitive control of saccadic eye movements. Brain Cogn. 2008;68(3):327–40.PubMedGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. 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.PubMedGoogle Scholar
  36. 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.PubMedPubMedCentralGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 38.
    Beck AT, Steer RA, Brown GK. Beck depression inventory-II. San Antonio. 1996;78(2):490–8.Google Scholar
  39. 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.PubMedGoogle Scholar
  40. 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.PubMedPubMedCentralGoogle Scholar
  41. 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.PubMedPubMedCentralGoogle Scholar
  42. 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. 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.PubMedGoogle Scholar
  44. 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.PubMedGoogle Scholar
  45. 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.PubMedPubMedCentralGoogle Scholar
  46. 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.PubMedGoogle Scholar
  47. 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.PubMedPubMedCentralGoogle Scholar
  48. 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.PubMedPubMedCentralGoogle Scholar
  49. 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.PubMedPubMedCentralGoogle Scholar
  50. 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.PubMedPubMedCentralGoogle Scholar
  51. 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.PubMedGoogle Scholar
  52. 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.PubMedPubMedCentralGoogle Scholar
  53. 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.PubMedGoogle Scholar
  54. 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. 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.PubMedGoogle Scholar
  56. 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.PubMedGoogle Scholar
  57. 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.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Hutton SB, Ettinger U. The antisaccade task as a research tool in psychopathology: a critical review. Psychophysiology. 2006;43(3):302–13.PubMedGoogle Scholar
  59. 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.PubMedGoogle Scholar
  60. 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.PubMedGoogle Scholar
  61. 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.PubMedGoogle Scholar
  62. 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.PubMedPubMedCentralGoogle Scholar
  63. 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.PubMedGoogle Scholar
  64. 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.PubMedGoogle Scholar
  65. 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.PubMedPubMedCentralGoogle Scholar
  66. 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.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Nikhil Banerjee
    • 1
    Email author
  • Roger C. McIntosh
    • 1
  • Gail Ironson
    • 1
  1. 1.Department of PsychologyUniversity of MiamiCoral GablesUSA

Personalised recommendations