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Vascular cognitive impairment and HIV-associated neurocognitive disorder: a new paradigm

  • Lucette A. CysiqueEmail author
  • Bruce J. Brew
Article

Abstract

In this review, we propose that vascular cognitive impairment (VCI), with relevance for the global HIV population, is fundamentally and clinically linked to the persistence of mild forms of HIV-associated neurocognitive disorders (HAND) in ageing people living with HIV infection (PLWH). After placing our review within the context of the general literature on HIV and ageing, we review non-VCI risks for dementia in ageing PLWH. We then present the recently updated VCI nomenclature and show that the neuropsychological and neuroimaging phenotypes of VCI and HAND are largely overlapping, suggesting that further research is needed to accurately distinguish them. We further link VCI and HAND at the mechanistic level by advancing the innovative proposal that the neuro-vascular unit (NVU) may represent the primary target of HIV-related brain injury in treated HIV infection. To this, we add the fundamental impact of mild and major VCI on the NVU. Importantly, we show that the potential contribution of vascular damage to overall brain damage in ageing PLWH is probably much higher than currently estimated because of methodological limitations, and because this research is only emerging. Finally, because all VCI risk factors are more prevalent, premature, and sometimes accelerated in the HIV population at large, we conclude that the probable total burden of VCI in the global HIV population is higher than in the general population and would need to be compared to chronic conditions such as type I diabetes and multiple sclerosis to account for the disease chronicity and lifelong treatment effects. Therefore, this review is also a call to action. Indeed, it is fully established that this amount of VCI burden is a major risk factor for dementia at aged 60+.

Keywords

HIV-associated neurocognitive disorders Vascular cognitive impairment HIV infection Ageing Dementia Stroke Vascular dementia Alzheimer’s disease Neurodegenerative diseases 

Notes

Acknowledgements

We would like to thank our research participants across all our research projects for their time. We thank A/Prof Melinda E. Cooper for her assistance in reviewing the manuscript.

Sources of funding

We would like to thank NHMRC project grants (APP568746; CIA/PI Cysique, APP1105808 CIA/PI Brew), NHMRC Career Development Fellowship (APP1045400; CIA/PI Cysique), and Peter Duncan Neuroscience Research Unit at St. Vincent’s Centre for Applied Medical Research (St. Vincent’s Hospital, Sydney; Director: Prof. Brew) for funding this work.

Compliance with ethical standards

Conflict of interest

Dr. Cysique reports no conflict of interest.

Prof. Brew reports personal fees from AbbVie, personal fees from ViiV, grants and personal fees from Biogen Idec, personal fees from Merck Sharpe and Dohme, and grants from National Institutes of Health, outside the submitted work.

References

  1. Akinyemi RO, Owolabi MO, Ihara M, Damasceno A, Ogunniyi A, Dotchin C, Paddick SM, Ogeng'o J, Walker R, Kalaria RN (2018) Stroke, cerebrovascular diseases and vascular cognitive impairment in Africa. Brain Res Bull.  https://doi.org/10.1016/j.brainresbull.2018.05.018
  2. Althoff KN, McGinnis KA, Wyatt CM, Freiberg MS, Gilbert C, Oursler KK, Rimland D, Rodriguez-Barradas MC, Dubrow R, Park LS, Skanderson M, Shiels MS, Gange SJ, Gebo KA, Justice AC (2015) Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clin Infect Dis 60:627–638PubMedCrossRefPubMedCentralGoogle Scholar
  3. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedPubMedCentralCrossRefGoogle Scholar
  4. Appay V, Sauce D (2008) Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol 214:231–241PubMedCrossRefPubMedCentralGoogle Scholar
  5. Appay V, Sauce D (2017) Assessing immune aging in HIV-infected patients. Virulence 8:529–538PubMedCrossRefPubMedCentralGoogle Scholar
  6. Atluri VS, Hidalgo M, Samikkannu T, Kurapati KR, Jayant RD, Sagar V, Nair MP (2015) Effect of human immunodeficiency virus on blood-brain barrier integrity and function: an update. Front Cell Neurosci 9:212PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bachani M, Sacktor N, McArthur JC, Nath A, Rumbaugh J (2013) Detection of anti-tat antibodies in CSF of individuals with HIV-associated neurocognitive disorders. J Neuro-Oncol 19:82–88Google Scholar
  8. Barnes RP, Lacson JC, Bahrami H (2017) HIV infection and risk of cardiovascular diseases beyond coronary artery disease. Curr Atheroscler Rep 19:20PubMedPubMedCentralCrossRefGoogle Scholar
  9. Benjamin LA, Bryer A, Lucas S, Stanley A, Allain TJ, Joekes E, Emsley H, Turnbull I, Downey C, Toh CH, Brown K, Brown D, Ison C, Smith C, Corbett EL, Nath A, Heyderman RS, Connor MD, Solomon T (2016) Arterial ischemic stroke in HIV: defining and classifying etiology for research studies. Neurol Neuroimmunol Neuroinflamm 3:e254PubMedPubMedCentralCrossRefGoogle Scholar
  10. Biesbroek JM, Weaver NA, Biessels GJ (2017) Lesion location and cognitive impact of cerebral small vessel disease. Clin Sci (Lond) 131:715–728CrossRefGoogle Scholar
  11. Bijker R, Choi JY, Ditangco R, Kiertiburanakul S, Lee MP, Siwamogsatham S, Pujari S, Ross J, Wong C, Wong WW, Yunihastuti E, Law M (2017) Cardiovascular disease and cardiovascular disease risk in HIV-positive populations in the Asian region. Open AIDS J 11:52–66PubMedPubMedCentralCrossRefGoogle Scholar
  12. Blokhuis C, Mutsaerts HJ, Cohen S, Scherpbier HJ, Caan MW, Majoie CB, Kuijpers TW, Reiss P, Wit FW, Pajkrt D (2017) Higher subcortical and white matter cerebral blood flow in perinatally HIV-infected children. Medicine (Baltimore) 96:e5891CrossRefGoogle Scholar
  13. Bouwman FH, Skolasky RL, Hes D, Selnes OA, Glass JD, Nance-Sproson TE, Royal W, Dal Pan GJ, McArthur JC (1998) Variable progression of HIV-associated dementia. Neurology 50:1814–1820PubMedCrossRefPubMedCentralGoogle Scholar
  14. Brew BJ (2016) Has HIV-associated neurocognitive disorders now transformed into vascular cognitive impairment? AIDS 30:2379–2380PubMedCrossRefPubMedCentralGoogle Scholar
  15. Brew BJ, Crowe SM, Landay A, Cysique LA, Guillemin G (2009) Neurodegeneration and ageing in the HAART era. J NeuroImmune Pharmacol 4:163–174PubMedCrossRefPubMedCentralGoogle Scholar
  16. Brunt SJ, Cysique LA, Lee S, Burrows S, Brew BJ, Price P (2016) Short communication: do cytomegalovirus antibody levels associate with age-related syndromes in HIV patients stable on antiretroviral therapy? AIDS Res Hum Retrovir 32:567–572PubMedCrossRefPubMedCentralGoogle Scholar
  17. Carnethon MR, Pu J, Howard G, Albert MA, Anderson CAM, Bertoni AG, Mujahid MS, Palaniappan L, Taylor HA Jr, Willis M, Yancy CW (2017) Cardiovascular health in African Americans: a scientific statement from the American Heart Association. Circulation 136:e393–e423PubMedCrossRefPubMedCentralGoogle Scholar
  18. Chow FC, Price RW, Hsue PY, Kim AS (2017) Greater risk of stroke of undetermined etiology in a contemporary HIV-infected cohort compared with uninfected individuals. J Stroke Cerebrovasc Dis 26:1154–1160PubMedPubMedCentralCrossRefGoogle Scholar
  19. Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA (2012) Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system. J Acquir Immune Defic Syndr 60:351–358PubMedPubMedCentralCrossRefGoogle Scholar
  20. Christopher B, Nadine RC, Mohamad AH, Ahmed K, Subodh V, Mohammed AO (2018) Peripheral artery disease among indigenous Canadians: what do we know? Can J Surg 61:305–310PubMedPubMedCentralGoogle Scholar
  21. Clifford KM, Samboju V, Cobigo Y, Milanini B, Marx GA, Hellmuth JM, Rosen HJ, Kramer JH, Allen IE, Valcour VG (2017) Progressive brain atrophy despite persistent viral suppression in HIV patients older than 60 years. J Acquir Immune Defic Syndr 76:289–297PubMedPubMedCentralCrossRefGoogle Scholar
  22. Cody SL, Vance DE (2016) The neurobiology of HIV and its impact on cognitive reserve: a review of cognitive interventions for an aging population. Neurobiol Dis 92:144–156PubMedCrossRefPubMedCentralGoogle Scholar
  23. Cole JH, Underwood J, Caan MW, De Francesco D, van Zoest RA, Leech R, Wit FW, Portegies P, Geurtsen GJ, Schmand BA, Schim van der Loeff MF, Franceschi C, Sabin CA, Majoie CB, Winston A, Reiss P, Sharp DJ (2017) Increased brain-predicted aging in treated HIV disease. Neurology 88:1349–1357PubMedPubMedCentralCrossRefGoogle Scholar
  24. Cummins D, Waters D, Aggar C, Crawford D, Fethney J, O'Connor C (2018) Voices from Australia—concerns about HIV associated neurocognitive disorder. AIDS Care 30:609–617PubMedCrossRefPubMedCentralGoogle Scholar
  25. Cysique LA, Bain MP, Brew BJ, Murray JM (2011) The burden of HIV-associated neurocognitive impairment in Australia and its estimates for the future. Sex Health 8:541–550PubMedCrossRefPubMedCentralGoogle Scholar
  26. Cysique LA, Brew BJ (2009) Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev 19:169–185PubMedCrossRefPubMedCentralGoogle Scholar
  27. Cysique LA, Brew BJ (2014) The effects of HIV and aging on brain functions: proposing a research framework and update on last 3 years’ findings. Curr Opin HIV AIDS 9:355–364PubMedCrossRefPubMedCentralGoogle Scholar
  28. Cysique LA, Heaton RK, Kamminga J, Lane T, Gates TM, Moore DM, Hubner E, Carr A, Brew BJ (2014) HIV-associated neurocognitive disorder in Australia: a case of a high-functioning and optimally treated cohort and implications for international neuroHIV research. J Neuro-Oncol 20:258–268Google Scholar
  29. Cysique LA, Moffat K, Moore DM, Lane TA, Davies NW, Carr A, Brew BJ, Rae C (2013) HIV, vascular and aging injuries in the brain of clinically stable HIV-infected adults: a (1)H MRS study. PLoS One 8:e61738PubMedPubMedCentralCrossRefGoogle Scholar
  30. Cysique LA, Soares JR, Geng G, Scarpetta M, Moffat K, Green M, Brew BJ, Henry RG, Rae C (2017) White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration. J Neuro-Oncol 23:539–547Google Scholar
  31. Dahl V, Peterson J, Fuchs D, Gisslen M, Palmer S, Price RW (2014) Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation. AIDS 28:2251–2258PubMedPubMedCentralCrossRefGoogle Scholar
  32. Dawood H, Hassan-Moosa R, Zuma NY, Naidoo K (2018) Mortality and treatment response amongst HIV-infected patients 50 years and older accessing antiretroviral services in South Africa. BMC Infect Dis 18:168PubMedPubMedCentralCrossRefGoogle Scholar
  33. de Roos A, van der Grond J, Mitchell G, Westenberg J (2017) Magnetic resonance imaging of cardiovascular function and the brain: is dementia a cardiovascular-driven disease? Circulation 135:2178–2195PubMedPubMedCentralCrossRefGoogle Scholar
  34. Deckers K, van Boxtel MP, Schiepers OJ, de Vugt M, Munoz Sanchez JL, Anstey KJ, Brayne C, Dartigues JF, Engedal K, Kivipelto M, Ritchie K, Starr JM, Yaffe K, Irving K, Verhey FR, Kohler S (2015) Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies. Int J Geriatr Psychiatry 30:234–246PubMedCrossRefGoogle Scholar
  35. Durand M, Sheehy O, Baril JG, LeLorier J, Tremblay CL (2013) Risk of spontaneous intracranial hemorrhage in HIV-infected individuals: a population-based cohort study. J Stroke Cerebrovasc Dis 22:e34–e41PubMedCrossRefGoogle Scholar
  36. Ford E, Greenslade N, Paudyal P, Bremner S, Smith HE, Banerjee S, Sadhwani S, Rooney P, Oliver S, Cassell J (2018) Predicting dementia from primary care records: a systematic review and meta-analysis. PLoS One 13:e0194735PubMedPubMedCentralCrossRefGoogle Scholar
  37. Friis-Moller N, Thiebaut R, Reiss P, Weber R, Monforte AD, De Wit S, El-Sadr W, Fontas E, Worm S, Kirk O, Phillips A, Sabin CA, Lundgren JD, Law MG (2010) Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil 17:491–501PubMedCrossRefGoogle Scholar
  38. Fulop T, Witkowski JM, Bourgade K, Khalil A, Zerif E, Larbi A, Hirokawa K, Pawelec G, Bocti C, Lacombe G, Dupuis G, Frost EH (2018) Can an infection hypothesis explain the beta amyloid hypothesis of Alzheimer’s disease? Front Aging Neurosci 10:224PubMedPubMedCentralCrossRefGoogle Scholar
  39. Gates TM, Cysique LA (2016) The chronicity of HIV infection should drive the research strategy of NeuroHIV treatment studies: a critical review. CNS Drugs 30:53–69PubMedPubMedCentralCrossRefGoogle Scholar
  40. GBD 2015 HIV Collaborators (2016) Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015. Lancet HIV 3:e361–e387CrossRefGoogle Scholar
  41. Gelman BB (2015) Neuropathology of HAND with suppressive antiretroviral therapy: encephalitis and neurodegeneration reconsidered. Curr HIV/AIDS Rep 12:272–279PubMedPubMedCentralCrossRefGoogle Scholar
  42. Gelman BB, Chen T, Lisinicchia JG, Soukup VM, Carmical JR, Starkey JM, Masliah E, Commins DL, Brandt D, Grant I, Singer EJ, Levine AJ, Miller J, Winkler JM, Fox HS, Luxon BA, Morgello S (2012) The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment. PLoS One 7:e46178PubMedPubMedCentralCrossRefGoogle Scholar
  43. Giuliano M, Pirillo MF, Liotta G, Andreotti M, Jere H, Sagno JB, Ciccacci F, Amici R, Marazzi MC, Vella S, Palombi L, Mancinelli S (2017) High CMV IgG antibody levels are associated to a lower CD4+ RESPONSE to antiretroviral therapy in HIV-infected women. J Clin Virol 96:17–19PubMedCrossRefPubMedCentralGoogle Scholar
  44. Glass JD, Fedor H, Wesselingh SL, McArthur JC (1995) Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia. Ann Neurol 38:755–762PubMedCrossRefPubMedCentralGoogle Scholar
  45. Goodkin K, Miller EN, Cox C, Reynolds S, Becker JT, Martin E, Selnes OA, Ostrow DG, Sacktor NC (2017) Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study. Lancet HIV 4:e411–e422PubMedPubMedCentralCrossRefGoogle Scholar
  46. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:2672–2713PubMedPubMedCentralCrossRefGoogle Scholar
  47. Gott C, Gates T, Dermody N, Brew BJ, Cysique LA (2017) Cognitive change trajectories in virally suppressed HIV-infected individuals indicate high prevalence of disease activity. PLoS One 12:e0171887PubMedPubMedCentralCrossRefGoogle Scholar
  48. Grant I, Franklin DR Jr, Deutsch R, Woods SP, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Collier AC, Marra CM, Clifford DB, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Smith DM, Heaton RK (2014) Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology 82:2055–2062PubMedPubMedCentralCrossRefGoogle Scholar
  49. Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, Berti A, Rossi E, Roverato A, Palella F (2011) Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 53:1120–1126PubMedCrossRefPubMedCentralGoogle Scholar
  50. Guaraldi G, Palella FJ Jr (2017) Clinical implications of aging with HIV infection: perspectives and the future medical care agenda. Aids 31(Suppl 2):S129–S135PubMedCrossRefPubMedCentralGoogle Scholar
  51. Gutierrez J, Albuquerque ALA, Falzon L (2017) HIV infection as vascular risk: a systematic review of the literature and meta-analysis. PLoS One 12:e0176686PubMedPubMedCentralCrossRefGoogle Scholar
  52. Gutierrez J, Byrd D, Yin MT, Morgello S (2018) Relationship between brain arterial pathology and neurocognitive performance among individuals with human immunodeficiency virus. Clin Infect Dis 11Google Scholar
  53. Gyaneshwar R, Naidu S, Raban MZ, Naidu S, Linhart C, Morrell S, Tukana I, Taylor R (2016) Absolute cardiovascular risk in a Fiji medical zone. BMC Public Health 16:128PubMedPubMedCentralCrossRefGoogle Scholar
  54. Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E, Alger J, Singer E, Campbell T, Yiannoutsos C, Cohen R, Navia B (2011) Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. Aids 25:625–633PubMedPubMedCentralCrossRefGoogle Scholar
  55. Hatleberg CI, Lundgren JD, Ryom L (2017) Are we successfully managing cardiovascular disease in people living with HIV? Curr Opin HIV AIDS 12:594–603PubMedCrossRefPubMedCentralGoogle Scholar
  56. Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 75:2087–2096PubMedPubMedCentralCrossRefGoogle Scholar
  57. Helman AM, Murphy MP (2016) Vascular cognitive impairment: modeling a critical neurologic disease in vitro and in vivo. Biochim Biophys Acta 1862:975–982PubMedCrossRefPubMedCentralGoogle Scholar
  58. Holloway CJ, Boccara F (2017) HIV-related cardiovascular disease: closing the gap in mortality. Curr Opin HIV AIDS 12:509–512PubMedCrossRefPubMedCentralGoogle Scholar
  59. Horsburgh K, Wardlaw JM, van Agtmael T, Allan SM, Ashford MLJ, Bath PM, Brown R, Berwick J, Cader MZ, Carare RO, Davis JB, Duncombe J, Farr TD, Fowler JH, Goense J, Granata A, Hall CN, Hainsworth AH, Harvey A, Hawkes CA, Joutel A, Kalaria RN, Kehoe PG, Lawrence CB, Lockhart A, Love S, Macleod MR, Macrae IM, Markus HS, McCabe C, McColl BW, Meakin PJ, Miller A, Nedergaard M, O'Sullivan M, Quinn TJ, Rajani R, Saksida LM, Smith C, Smith KJ, Touyz RM, Trueman RC, Wang T, Williams A, Williams SCR, Work LM (2018) Small vessels, dementia and chronic diseases—molecular mechanisms and pathophysiology. Clin Sci (Lond) 132:851–868CrossRefGoogle Scholar
  60. Hsue PY, Deeks SG, Hunt PW (2012) Immunologic basis of cardiovascular disease in HIV-infected adults. J Infect Dis 205(Suppl 3):S375–S382PubMedPubMedCentralCrossRefGoogle Scholar
  61. Hsue PY, Waters DD (2017) Heart failure in persons living with HIV infection. Curr Opin HIV AIDS 12:534–539PubMedCrossRefPubMedCentralGoogle Scholar
  62. Hyle EP, Mayosi BM, Middelkoop K, Mosepele M, Martey EB, Walensky RP, Bekker LG, Triant VA (2017) The association between HIV and atherosclerotic cardiovascular disease in sub-Saharan Africa: a systematic review. BMC Public Health 17:954PubMedPubMedCentralCrossRefGoogle Scholar
  63. Johnson Shen M, Freeman R, Karpiak S, Brennan-Ing M, Seidel L, Siegler EL (2018) The intersectionality of stigmas among key populations of older adults affected by HIV: a thematic analysis. Clin Gerontol 26:1–13CrossRefGoogle Scholar
  64. Kallianpur AR, Gittleman H, Letendre S, Ellis R, Barnholtz-Sloan JS, Bush WS, Heaton R, Samuels DC, Franklin DR Jr, Rosario-Cookson D, Clifford DB, Collier AC, Gelman B, Marra CM, McArthur JC, McCutchan JA, Morgello S, Grant I, Simpson D, Connor JR, Hulgan T (2018) Cerebrospinal fluid ceruloplasmin, haptoglobin, and vascular endothelial growth factor are associated with neurocognitive impairment in adults with HIV infection. Mol Neurobiol 12:018–1329Google Scholar
  65. Kouassi LK, Doumbia-Ouattara M (2017) Acute onset vascular dementia with bi-thalamic infarct in an HIV-positive subject. Am J Case Rep 18:1145–1147PubMedPubMedCentralCrossRefGoogle Scholar
  66. Lacson JCA, Barnes RP, Bahrami H (2017) Coronary artery disease in HIV-infected patients: downside of living longer. Curr Atheroscler Rep 19:18PubMedPubMedCentralCrossRefGoogle Scholar
  67. Lagathu C, Cossarizza A, Bereziat V, Nasi M, Capeau J, Pinti M (2017) Basic science and pathogenesis of ageing with HIV: potential mechanisms and biomarkers. Aids 31(Suppl 2):S105–S119PubMedCrossRefPubMedCentralGoogle Scholar
  68. Le LT, Spudich SS (2016) HIV-associated neurologic disorders and central nervous system opportunistic infections in HIV. Semin Neurol 36:373–381PubMedCrossRefPubMedCentralGoogle Scholar
  69. Letendre S, Bharti A, Perez-Valero I, Hanson B, Franklin D, Woods SP, Gianella S, de Oliveira MF, Heaton RK, Grant I, Landay AL, Lurain N (2018). Higher anti-cytomegalovirus immunoglobulin G concentrations are associated with worse neurocognitive performance during suppressive antiretroviral therapy. Clin Infect Dis 67:770–777Google Scholar
  70. Lipnicki DM, Crawford JD, Dutta R, Thalamuthu A, Kochan NA, Andrews G, Lima-Costa MF, Castro-Costa E, Brayne C, Matthews FE, Stephan BC, Lipton RB, Katz MJ, Ritchie K, Scali J, Ancelin ML, Scarmeas N, Yannakoulia M, Dardiotis E, Lam LC, Wong CH, Fung AW, Guaita A, Vaccaro R, Davin A, Kim KW, Han JW, Kim TH, Anstey KJ, Cherbuin N, Butterworth P, Scazufca M, Kumagai S, Chen S, Narazaki K, Ng TP, Gao Q, Reppermund S, Brodaty H, Lobo A, Lopez-Anton R, Santabarbara J, Sachdev PS (2017) Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study. PLoS Med 14:e1002261PubMedPubMedCentralCrossRefGoogle Scholar
  71. Mayeda ER, Tchetgen Tchetgen EJ, Power MC, Weuve J, Jacqmin-Gadda H, Marden JR, Vittinghoff E, Keiding N, Glymour MM (2016) A simulation platform for quantifying survival bias: an application to research on determinants of cognitive decline. Am J Epidemiol 184:378–387PubMedPubMedCentralCrossRefGoogle Scholar
  72. McCrary AW, Nduka CU, Stranges S, Bloomfield GS (2017) Features of cardiovascular disease in low-income and middle-income countries in adults and children living with HIV. Curr Opin HIV AIDS 12:579–584PubMedCrossRefPubMedCentralGoogle Scholar
  73. McHutchison CA, Backhouse EV, Cvoro V, Shenkin SD, Wardlaw JM (2017) Education, socioeconomic status, and intelligence in childhood and stroke risk in later life: a meta-analysis. Epidemiology 28:608–618PubMedCrossRefPubMedCentralGoogle Scholar
  74. Milanini B, Valcour V (2017) Differentiating HIV-associated neurocognitive disorders from Alzheimer’s disease: an emerging issue in geriatric NeuroHIV. Curr HIV/AIDS Rep 14:123–132PubMedPubMedCentralCrossRefGoogle Scholar
  75. Moulignier A, Savatovsky J, Assoumou L, Lescure FX, Lamirel C, Godin O, Valin N, Tubiana R, Canestri A, Roux P, Sadik JC, Salomon L, Abrivard M, Katlama C, Yazdanpanah Y, Pialoux G, Girard PM, Costagliola D (2018) Silent cerebral small-vessel disease is twice as prevalent in middle-aged individuals with well-controlled, combination antiretroviral therapy-treated human immunodeficiency virus (HIV) than in HIV-uninfected individuals. Clin Infect Dis 66:1762–1769PubMedCrossRefPubMedCentralGoogle Scholar
  76. Nedelcovych MT, Manning AA, Semenova S, Gamaldo C, Haughey NJ, Slusher BS (2017) The psychiatric impact of HIV. ACS Chem Neurosci 8:1432–1434PubMedPubMedCentralCrossRefGoogle Scholar
  77. Nichols MJ, Gates TM, Soares JR, Moffat KJ, Rae CD, Brew BJ, Cysique LA (2018) Atrophic brain signatures of mild forms of neurocognitive impairment in virally suppressed HIV infection. AIDS.  https://doi.org/10.1097/QAD.0000000000002042
  78. Panza F, Solfrizzi V, Logroscino G, Maggi S, Santamato A, Seripa D, Pilotto A (2012) Current epidemiological approaches to the metabolic-cognitive syndrome. J Alzheimers Dis 30(Suppl 2):S31–S75PubMedCrossRefPubMedCentralGoogle Scholar
  79. Paratz ED, Cunningham NJ, MacIsaac AI (2016) The cardiac complications of methamphetamines. Heart Lung Circ 25:325–332PubMedCrossRefPubMedCentralGoogle Scholar
  80. Patel S, Parikh NU, Aalinkeel R, Reynolds JL, Dmello R, Schwartz SA, Mahajan SD (2018) United States National Trends in mortality, length of stay (LOS) and associated costs of cognitive impairment in HIV population from 2005 to 2014. AIDS Behav 22:3198–3208PubMedCrossRefPubMedCentralGoogle Scholar
  81. Peng SL, Chen X, Li Y, Rodrigue KM, Park DC, Lu H (2018) Age-related changes in cerebrovascular reactivity and their relationship to cognition: a four-year longitudinal study. Neuroimage 174:257–262PubMedCrossRefPubMedCentralGoogle Scholar
  82. Petoumenos K, Reiss P, Ryom L, Rickenbach M, Sabin CA, El-Sadr W, d'Arminio Monforte A, Phillips AN, De Wit S, Kirk O, Dabis F, Pradier C, Lundgren JD, Law MG (2014) Increased risk of cardiovascular disease (CVD) with age in HIV-positive men: a comparison of the D:A:D CVD risk equation and general population CVD risk equations. HIV Med 15:595–603PubMedPubMedCentralGoogle Scholar
  83. Pfefferbaum A, Zahr NM, Sassoon SA, Kwon D, Pohl KM, Sullivan EV (2018) Accelerated and premature aging characterizing regional cortical volume loss in human immunodeficiency virus infection: contributions from alcohol, substance use, and hepatitis C coinfection. Biol Psychiatry Cogn Neurosci Neuroimaging 3:844–859PubMedCrossRefPubMedCentralGoogle Scholar
  84. Rajasuriar R, Chong ML, Ahmad Bashah NS, Abdul Aziz SA, McStea M, Lee ECY, Wong PL, Azwa I, Syed Omar SF, Lai PSM, Ponampalavanar S, Crowe SM, Lewin SR, Kamaruzzaman SB, Kamarulzaman A (2017) Major health impact of accelerated aging in young HIV-infected individuals on antiretroviral therapy. Aids 31:1393–1403PubMedCrossRefPubMedCentralGoogle Scholar
  85. Raposeiras-Roubin S, Abu-Assi E, Iniguez-Romo A (2017) Tobacco, illicit drugs use and risk of cardiovascular disease in patients living with HIV. Curr Opin HIV AIDS 12:523–527PubMedCrossRefPubMedCentralGoogle Scholar
  86. Rasmussen LD, Engsig FN, Christensen H, Gerstoft J, Kronborg G, Pedersen C, Obel N (2011) Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study. Aids 25:1637–1646PubMedCrossRefPubMedCentralGoogle Scholar
  87. Rasmussen LD, May MT, Kronborg G, Larsen CS, Pedersen C, Gerstoft J, Obel N (2015) Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study. Lancet HIV 2:e288–e298PubMedCrossRefPubMedCentralGoogle Scholar
  88. Rubin LH, Maki PM, Springer G, Benning L, Anastos K, Gustafson D, Villacres MC, Jiang X, Adimora AA, Waldrop-Valverde D, Vance DE, Bolivar H, Alden C, Martin EM, Valcour VG (2017) Cognitive trajectories over 4 years among HIV-infected women with optimal viral suppression. Neurology 89:1594–1603PubMedPubMedCentralCrossRefGoogle Scholar
  89. Saloner R, Cysique LA (2017) HIV-associated neurocognitive disorders: a global perspective. J Int Neuropsychol Soc 23:860–869PubMedPubMedCentralCrossRefGoogle Scholar
  90. Schouten J, Wit FW, Stolte IG, Kootstra NA, van der Valk M, Geerlings SE, Prins M, Reiss P (2014) Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study. Clin Infect Dis 59:1787–1797PubMedCrossRefPubMedCentralGoogle Scholar
  91. Schwartz M, Baruch K (2014) Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: boosting autoimmunity to fight-off chronic neuroinflammation. J Autoimmun 54:8–14PubMedCrossRefPubMedCentralGoogle Scholar
  92. Sico JJ, Chang CC, So-Armah K, Justice AC, Hylek E, Skanderson M, McGinnis K, Kuller LH, Kraemer KL, Rimland D, Bidwell Goetz M, Butt AA, Rodriguez-Barradas MC, Gibert C, Leaf D, Brown ST, Samet J, Kazis L, Bryant K, Freiberg MS (2015) HIV status and the risk of ischemic stroke among men. Neurology 84:1933–1940PubMedPubMedCentralCrossRefGoogle Scholar
  93. Skrobot OA, Black SE, Chen C, DeCarli C, Erkinjuntti T, Ford GA, Kalaria RN, O'Brien J, Pantoni L, Pasquier F, Roman GC, Wallin A, Sachdev P, Skoog I, Ben-Shlomo Y, Passmore AP, Love S, Kehoe PG (2018) Progress toward standardized diagnosis of vascular cognitive impairment: guidelines from the Vascular Impairment of Cognition Classification Consensus Study. Alzheimers Dement 14:280–292PubMedCrossRefPubMedCentralGoogle Scholar
  94. Skrobot OA, O'Brien J, Black S, Chen C, DeCarli C, Erkinjuntti T, Ford GA, Kalaria RN, Pantoni L, Pasquier F, Roman GC, Wallin A, Sachdev P, Skoog I, Ben-Shlomo Y, Passmore AP, Love S, Kehoe PG (2017) The vascular impairment of cognition classification consensus study. Alzheimers Dement 13:624–633PubMedCrossRefPubMedCentralGoogle Scholar
  95. Smail RC, Brew BJ (2018) HIV-associated neurocognitive disorder. Handb Clin Neurol 152:75–97PubMedCrossRefPubMedCentralGoogle Scholar
  96. Smit M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, Sighem A, de Wolf F, Hallett TB (2015) Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis 15:810–818PubMedPubMedCentralCrossRefGoogle Scholar
  97. Stone L, Looby SE, Zanni MV (2017) Cardiovascular disease risk among women living with HIV in North America and Europe. Curr Opin HIV AIDS 12:585–593PubMedPubMedCentralCrossRefGoogle Scholar
  98. Stover J, Brown T, Puckett R, Peerapatanapokin W (2017) Updates to the Spectrum/Estimations and Projections Package model for estimating trends and current values for key HIV indicators. Aids 31(Suppl 1):S5–S11PubMedCrossRefPubMedCentralGoogle Scholar
  99. Su T, Mutsaerts HJ, Caan MW, Wit FW, Schouten J, Geurtsen GJ, Sharp DJ, Prins M, Richard E, Portegies P, Reiss P, Majoie CB (2017) Cerebral blood flow and cognitive function in HIV-infected men with sustained suppressed viremia on combination antiretroviral therapy. Aids 31:847–856PubMedCrossRefPubMedCentralGoogle Scholar
  100. Tang H, Mao Y, Tang W, Han J, Xu J, Li J (2018) Late for testing, early for antiretroviral therapy, less likely to die: results from a large HIV cohort study in China, 2006-2014. BMC Infect Dis 18:272Google Scholar
  101. Terpstra AR, Worthington C, Ibanez-Carrasco F, O'Brien KK, Yamamoto A, Chan Carusone S, Baltzer Turje R, McDougall P, Granger W, Thompson V, DeSousa M, Creal L, Rae A, Medina C, Morley E, Rourke SB (2018) “I’m just forgetting and I don’t know why”: exploring how people living with HIV-associated neurocognitive disorder view, manage, and obtain support for their cognitive difficulties. Qual Health Res 28:859–872PubMedCrossRefPubMedCentralGoogle Scholar
  102. The Antiretroviral Therapy Cohort Collaboration (2008) Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 372:293–299PubMedCentralCrossRefGoogle Scholar
  103. Triant VA, Grinspoon SK (2017) Epidemiology of ischemic heart disease in HIV. Curr Opin HIV AIDS 12:540–547PubMedPubMedCentralCrossRefGoogle Scholar
  104. Ulfhammer G, Eden A, Mellgren A, Fuchs D, Zetterberg H, Hagberg L, Nilsson S, Yilmaz A, Gisslen M (2018) Persistent central nervous system immune activation following more than 10 years of effective HIV antiretroviral treatment. Aids 32:2171–2178PubMedCrossRefPubMedCentralGoogle Scholar
  105. Underwood J, De Francesco D, Leech R, Sabin CA, Winston A (2018) Medicalising normality? Using a simulated dataset to assess the performance of different diagnostic criteria of HIV-associated cognitive impairment. PLoS One 13:e0194760PubMedPubMedCentralCrossRefGoogle Scholar
  106. van der Flier WM, Skoog I, Schneider JA, Pantoni L, Mok V, Chen CLH, Scheltens P (2018) Vascular cognitive impairment. Nat Rev Dis Primers 4:18003PubMedCrossRefPubMedCentralGoogle Scholar
  107. van Zoest RA, van den Born BH, Reiss P (2017) Hypertension in people living with HIV. Curr Opin HIV AIDS 12:513–522PubMedCrossRefPubMedCentralGoogle Scholar
  108. Vinikoor MJ, Napravnik S, Floris-Moore M, Wilson S, Huang DY, Eron JJ (2013) Incidence and clinical features of cerebrovascular disease among HIV-infected adults in the Southeastern United States. AIDS Res Hum Retrovir 29:1068–1074PubMedCrossRefPubMedCentralGoogle Scholar
  109. Vivithanaporn P, Heo G, Gamble J, Krentz HB, Hoke A, Gill MJ, Power C (2010) Neurologic disease burden in treated HIV/AIDS predicts survival: a population-based study. Neurology 75:1150–1158PubMedPubMedCentralCrossRefGoogle Scholar
  110. Weuve J, Proust-Lima C, Power MC, Gross AL, Hofer SM, Thiébaut R, Chêne G, Glymour MM, Dufouil C (2015) Guidelines for reporting methodological challenges and evaluating potential bias in dementia research. Alzheimers Dement 11:1098–1109PubMedPubMedCentralCrossRefGoogle Scholar
  111. Wiemers PD, Marney L, Yadav S, Tam R, Fraser JF (2018) An overview of indigenous Australian disadvantage in terms of ischaemic heart disease. Heart Lung Circ 27:1274–1284PubMedCrossRefPubMedCentralGoogle Scholar
  112. Wright ST, Petoumenos K, Boyd M, Carr A, Downing S, O'Connor CC, Grotowski M, Law MG (2013) Ageing and long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience. HIV Med 14:208–216PubMedCrossRefPubMedCentralGoogle Scholar
  113. Xia X, Jiang Q, McDermott J, Han JDJ (2018) Aging and Alzheimer’s disease: comparison and associations from molecular to system level. Aging Cell 17:1474–9726CrossRefGoogle Scholar
  114. Xu S, Vucic EA, Shaipanich T, Lam S, Lam W, Montaner JS, Sin DD, Paul Man SF, Leung JM (2018) Decreased telomere length in the small airway epithelium suggests accelerated aging in the lungs of persons living with human immunodeficiency virus (HIV). Respir Res 19:117PubMedPubMedCentralCrossRefGoogle Scholar
  115. Zwanenburg JJM, van Osch MJP (2017) Targeting cerebral small vessel disease with MRI. Stroke 48:3175–3182PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2019

Authors and Affiliations

  1. 1.Neuroscience Research AustraliaRandwickAustralia
  2. 2.UNSW MedicineUNSW SydneySydneyAustralia
  3. 3.Peter Duncan Neuroscience Research UnitSt. Vincent’s Centre for Applied Medical ResearchDarlinghurstAustralia
  4. 4.Department of NeurologySt. Vincent’s HospitalDarlinghurstAustralia
  5. 5.Department of ImmunologySt. Vincent’s HospitalDarlinghurstAustralia

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