Abstract
This chapter will address the issue of risk for HIV-associated neurocognitive disorder (HAND), focusing on HIV-associated dementia (HAD), among persons living with HIV in relationship to the risk for other dementias. Advances in effective antiretroviral therapy (ART) have led to an increase in the prevalence of older persons surviving with HIV – in addition to older persons who become infected by HIV later in life. Hence, HIV is no longer a disease of younger persons, and additional attention has been brought to bear against the plight of older persons living with HIV – not only as it pertains to treatment but also to prevention. The additional risk caused by aging among older persons living with HIV is complex to asses, and HIV infection is a research area that requires a robust approach to multiple other factors causing neurocognitive impairment with older age. The long-term and potentially neurotoxic exposure to ART and the deleterious consequences of chronic infection with HIV and its associated neuro-inflammation have been described for health. This aids in the understanding of dementia risk factors in this patient population, but the comorbidities (HIV- and non-HIV-associated) occurring among older persons living with HIV must also be addressed to properly assess the overall impact on dementia risk in this group. This need also warrants our examination of the risk factors for other dementias (and comorbid dementias) in persons living with HIV versus the general population through the assessment and quantification of modifiable and non-modifiable risk factors identified as major contributors toward dementia.
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References
Akhtar RS, Xie SX, Brennan L, Pontecorvo MJ, Hurtig HI, Trojanowski JQ, Weintraub D, Siderowf AD (2016) Amyloid-beta positron emission tomography imaging of Alzheimer’s pathology in Parkinson’s disease dementia. Mov Disord Clin Pract 3:367–375
Akkina R, Allam A, Balazs A et al (2016) Improvements and limitations of humanized mouse models for HIV research: NIH/NIAID “meet the experts” 2015 workshop summary. AIDS Res Hum Retrovir 32(2):109–119. https://doi.org/10.1089/aid.2015.0258
Aung HL et al (2019) How all-type dementia risk factors and modifiable risk interventions may be relevant to the first-generation aging with HIV infection? Eur Geriatr Med 10(2):227–238. https://doi.org/10.1007/s41999-019-00164-6
Azad NA et al (2007) Gender differences in dementia risk factors. Gend Med 4(2):120–129. https://doi.org/10.1016/s1550-8579(07)80026-x
Bagetta G, Piccirilli S, Del Duca C et al (2004 Feb) Inducible nitric oxide synthase is involved in the mechanisms of cocaine enhanced neuronal apoptosis induced by HIV-1 gp120 in the neocortex of rat. Neurosci Lett 356(3):183–186. https://doi.org/10.1016/j.neulet.2003.11.065
Bahia VS, Takada LT, Deramecourt V (2013) Neuropathology of frontotemporal lobar degeneration: a review. Dement Neuropsychol 7(1):19–26. https://doi.org/10.1590/S1980-57642013DN70100004
Baumgart M et al (2015) Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective. Alzheimers Dement 11(6):718–726. https://doi.org/10.1016/j.jalz.2015.05.016
Becker JT, Maruca V, Kingsley LA et al (2012) Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology 54(2):113–121
Becker JT, Martinson JJ, Penugonda S et al (2015) J Neurovirol 21:24. https://doi.org/10.1007/s13365-014-0290-2
Brown A, Sacktor N, Marder K et al (2012) CCL3L1 gene copy number in individuals with and without HIV-associated neurocognitive disorder. Curr Biomark Find 2012(2):1–6. https://doi.org/10.2147/CBF.S27685
Brown LK, Kennard BD, Emslie GJ et al (2016) Effective treatment of depressive disorders in medical clinics for adolescents and young adults living with HIV: a controlled trial. J Acquir Immune Defic Syndr 71(1):38–46
Cardarelli R, Kertesz A, Knebl J (2010) Frontotemporal dementia: a review for primary care physicians. Am Fam Physician 82(11):1372–1377. https://www.aafp.org/afp/2010/1201/p1372.html
Carroll A, Brew B (2017) HIV-associated neurocognitive disorders: recent advances in pathogenesis, biomarkers, and treatment. F1000Res 6:312. https://doi.org/10.12688/f1000research.10651.1
Cassol E, Misra V, Morgello S, Kirk GD, Mehta SH, Gabuzda D (2015) Altered monoamine and acylcarnitine metabolites in HIV-positive and HIV-negative subjects with depression. J Acquir Immune Defic Syndr 69(1):18–28. https://doi.org/10.1097/QAI.0000000000000551
Chiesi A, Vella S, Dally LG et al (1996) Epidemiology of AIDS dementia complex in Europe. J Acquir Immune Defic Syndr Hum Retrovirol 11(1):39–44. https://doi.org/10.1097/00042560-199601010-00005
Coleman SM, Blashill AJ, Gandhi RT, Safren SA, Freudenreich O (2012) Impact of integrated and measurement-based depression care: clinical experience in an HIV clinic. Psychosomatics 53(1):51–57
Cykowski MD, Powell SZ, Schulz PE et al (2017) Hippocampal sclerosis in older patients: practical examples and guidance with a focus on cerebral age-related TDP-43 with sclerosis. Arch Pathol Lab Med 141(8):1113–1126
Cysique LA, Brew BJ (2019) Vascular cognitive impairment and HIV-associated neurocognitive disorder: a new paradigm. J Neurovirol 25(5):710–721
Dawson TM et al (2018) Animal models of neurodegenerative diseases. Nat Neurosci 21(10):1370–1379. https://doi.org/10.1038/s41593-018-0236-8
Do AN, Rosenberg ES, Sullivan PS, Beer L, Strine TW, Schulden JD, Fagan JL, Freedman MS, Skarbinski J (2014 Mar 24) Excess burden of depression among HIV-infected persons receiving medical care in the United States: data from the medical monitoring project and the behavioral risk factor surveillance system. PLoS One 9(3):e92842. https://doi.org/10.1371/journal.pone.0092842
Dolan M, Kulkarni H, Camargo J et al (2007) CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms. Nat Immunol 8:1324–1336
Donahoe R, Vlahov D (1998) Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 83(1–2):77–87. https://doi.org/10.1016/s0165-5728(97)00224-5
El-Hage N, Rodriguez M, Dever SM, Masvekar RR, Gewirtz DA, Shacka JJ (2015) HIV-1 and morphine regulation of autophagy in microglia: limited interactions in the context of HIV-1 infection and opioid abuse. J Virol 89(2):1024–1035. https://doi.org/10.1128/JVI.02022-14
Feneberg E, Gray E, Ansorge O, Talbot K, Turner MR (2018) Towards a TDP-43-based biomarker for ALS and FTLD. Mol Neurobiol 55(10):7789–7801. https://doi.org/10.1007/s12035-018-0947-6
Fjell AM, McEvoy L, Holland D, Dale AM, Walhovd KB, Alzheimer’s Disease Neuroimaging Initiative (2014) What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Prog Neurobiol 117:20–40. https://doi.org/10.1016/j.pneurobio.2014.02.004
Goodkin K, Wilkie FL, Concha M, Hinkin CH, Symes S, Baldewicz TT, Asthana D, Fujimura RK, Lee D, van Zuilen MH, Khamis I, Shapshak P, Eisdorfer C (2001) Aging and neuro-AIDS conditions and the changing spectrum of HIV-1-associated morbidity and mortality. J Clin Epidemiol 54(Suppl 1):S35–S43. https://doi.org/10.1016/S0895-4356(01)00445-0
Goodkin K, Hardy DJ, Singh D, Lopez E (2014) Diagnostic utility of the international HIV dementia scale for HIV-associated neurocognitive impairment and disorder in South Africa. J Neuropsychiatry Clin Neurosci 26(4):352–358. https://doi.org/10.1176/appi.neuropsych.13080178
Goodkin K, Miller E, Cox C, Reynolds S, Becker JT, Martin E, Selnes O, Ostrow D, Sacktor N (2017) Effect of aging on neurocognitive function by stage of HIV infection: evidence from the multi-center AIDS cohort study. Lancet HIV 4(9):e411–e422
Hammond ER, Crum RM, Treisman GJ et al (2016) Persistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study. J Neurovirol 22(4):479–487. https://doi.org/10.1007/s13365-015-0416-1
Heuer E, Rosen RF, Cintron A, Walker LC (2012) Nonhuman primate models of Alzheimer-like cerebral proteopathy. Curr Pharm Des 18(8):1159–1169
Hines LJ, Miller EN, Hinkin CH et al (2016) Brain Imaging Behav 10:640. https://doi.org/10.1007/s11682-015-9441-1
Irwin DJ, Hurtig HI (2018) The contribution of tau, amyloid-beta and alpha-synuclein pathology to dementia in lewy body disorders. J Alzheimers Dis Parkinsonism 8(4):444
Kaul M (2009) HIV-1 associated dementia: update on pathological mechanisms and therapeutic approaches. Curr Opin Neurol 22(3):315–320. https://doi.org/10.1097/wco.0b013e328329cf3c
Kennard B, Brown L, Hawkins L et al (2014) Development and implementation of health and wellness CBT for individuals with depression and HIV. Cogn Behav Pract 21(2):237–246. https://doi.org/10.1016/j.cbpra.2013.07.003
Kivipelto M, Mangialasche F, Ngandu T (2018) Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease. Nat Rev Neurol 14(11):653–666. https://doi.org/10.1038/s41582-018-0070-3
Kraft-Terry SD, Buch SJ, Fox HS, Gendelman HE (2009) A coat of many colors: neuroimmune crosstalk in human immunodeficiency virus infection. Neuron 64(1):133–145. https://doi.org/10.1016/j.neuron.2009.09.042
Kumar N, Chahroudi A, Silvestri G (2016) Animal models to achieve an HIV cure. Curr Opin HIV AIDS 11(4):432–441. https://doi.org/10.1097/COH.0000000000000290
Lee EB, Porta S, Michael Baer G et al (2017) Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration. Acta Neuropathol 134(1):65–78
Lennon MJ, Makkar SR, Crawford JD, Sachdev PS (2019) Midlife hypertension and Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis 71(1):307–316. https://doi.org/10.3233/jad-190474
Mackiewicz MM et al (2019) Pathogenesis of age-related HIV neurodegeneration. J Neurovirol 25(5):622–633. https://doi.org/10.1007/s13365-019-00728-z
Mathews S, Branch Woods A, Katano I, Makarov E, Thomas MB, Gendelman HE et al (2019) Human Interleukin-34 facilitates microglia-like cell differentiation and persistent HIV-1 infection in humanized mice. Mol Neurodegener 14(1):12. https://doi.org/10.1186/s13024-019-0311-y
Métral M, Darling K, Locatelli I et al (2019) The neurocognitive assessment in the metabolic and aging cohort (NAMACO) study: baseline participant profile. HIV Med 21(1):30–42. https://doi.org/10.1111/hiv.12795
Moore DJ, Arce M, Moseley S et al (2011) Family history of dementia predicts worse europsychological functioning among HIV-infected persons. J Neuropsychiatry Clin Neurosci 23(3):316–323. https://doi.org/10.1176/jnp.23.3.jnp316
Olivier I et al (2018) Risk factors and pathogenesis of HIV-associated neurocognitive disorder: the role of host genetics. Int J Mol Sci 19(11):3594. https://doi.org/10.3390/ijms19113594
Paulson H, Igo I (2011) Genetics of dementia. Semin Neurol 31(05):449–460. https://doi.org/10.1055/s-0031-1299784
Pence BW, Gaynes BN, Williams Q et al (2012) Assessing the effect of measurement-based care depression treatment on HIV medication adherence and health outcomes: rationale and design of the SLAM DUNC study. Contemp Clin Trials 33(4):828–838. https://doi.org/10.1016/j.cct.2012.04.002
Peterson J, Gisslen M, Zetterberg H, Fuchs D, Shacklett BL, Hagberg L, Yiannoutsos CT, Spudich SS, Price RW (2014) Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection. PLoS One 9(12):e116081. https://doi.org/10.1371/journal.pone.0116081
Pfefferbaum A et al (2014) Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled, longitudinal magnetic resonance imaging study. Neurobiol Aging 35(7):1755–1768. https://doi.org/10.1016/j.neurobiolaging.2014.01.008
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(10):844–859
Power C, Selnes OA, Grim JA, Mcarthur JC (1995) HIV dementia scale. PsycTESTS Dataset. https://doi.org/10.1037/t55375-000
Rahimian P, He JJ (2017) HIV/neuroAIDS biomarkers. Prog Neurobiol 157:117–132. https://doi.org/10.1016/j.pneurobio.2016.04.003
Reas ET (2017) Amyloid and tau pathology in normal cognitive aging. J Neurosci 37(32):7561–7563
Robertson KR, Kapoor C, Robertson WT, Fiscus S, Ford S, Hall CD (2004) No gender differences in the progression of nervous system disease in HIV infection. J Acquir Immune Defic Syndr 36(3):817–822. https://doi.org/10.1097/00126334-200407010-00008
Rubin LH, Neigh GN, Sundermann EE et al (2019) Curr Psychiatry Rep 21:94. https://doi.org/10.1007/s11920-019-1089-x
Ryan EL, Baird R, Mindt MR et al (2005) Neuropsychological impairment in racial/ethnic minorities with HIV infection and low literacy levels: effects of education and reading level in participant characterization. J Int Neuropsychol Soc 11(7):889–898. https://doi.org/10.1017/s1355617705051040
Sacktor NC, Wong M, Nakasujja N et al (2005) The international HIV dementia scale: a new rapid screening test for HIV dementia. AIDS 19(13):1367–1374. https://doi.org/10.1097/01.aids.0000180790.77379.3a
Satz P, Morgenstern H, Miller EN et al (1993) Low education as a possible risk factor for cognitive abnormalities in HIV-1. J Acquir Immune Defic Syndr 6(5):503–511. https://doi.org/10.1097/00126334-199305000-00011
Saylor D, Dickens AM, Sacktor N et al (2016) HIV-associated neurocognitive disorder–pathogenesis and prospects for treatment [published correction appears in Nat Rev Neurol. 2016 May;12(5):309]. Nat Rev Neurol 12(4):234–248. https://doi.org/10.1038/nrneurol.2016.27
Simoni JM, Safren SA, Manhart LE, Lyda K, Grossman CI, Rao D, Mimiaga MJ, Wong FY, Catz SL, Blank MB, DiClemente R, Wilson IB (2011) Challenges in addresing depression in HIV research: assessment, cultural context, and methods. AIDS Behav 15(2):376–388
Soontornniyomkij V, Moore DJ, Gouaux B et al (2012) Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers. AIDS 26(18):2327–2335. https://doi.org/10.1097/qad.0b013e32835a117c
Stern Y, Andrews H, Pittman J et al (1992) Diagnosis of dementia in a heterogeneous population: development of a neuropsychological paradigm-based diagnosis of dementia and quantified correction for the effects of education. Arch Neurol 49(5):453–460. https://doi.org/10.1001/archneur.1992.00530290035009
Theodore S, Cass WA, Nath A et al (2006) Inhibition of tumor necrosis factor-alpha signaling prevents human immunodeficiency virus-1 protein Tat and methamphetamine interaction. Neurobiol Dis 23(3):663–668. https://doi.org/10.1016/j.nbd.2006.05.005
Tozzi V, Balestra P, Vlassi C, Salvatori MF (2007) Authorʼs response to “Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment”. J Acquir Immune Defic Syndr 46(5):657–658. https://doi.org/10.1097/qai.0b013e318157b0f0
Uthman OA, Magidson JF, Safren SA, Nachega JB (2014) Depression and adherence to antiretroviral therapy in low-, middle- and high-income countries: a systematic review and meta-analysis. Curr HIV/AIDS Rep 11(3):291–307. https://doi.org/10.1007/s11904-014-0220-1
van der Zande JJ, Booij J, Scheltens P, Raijmakers PG, Lemstra AW (2016) [(123)]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies. Eur J Nucl Med Mol Imaging 43(6):1060–1066. https://doi.org/10.1007/s00259-016-3312-x
Wium-Andersen IK, Osler M, Jørgensen MB et al (2019) Antidiabetic medication and risk of dementia in patients with type 2 diabetes: a nested case–control study. Eur J Endocrinol 181(5):499–507. https://doi.org/10.1530/eje-19-0259
Wong MH, Robertson K, Nakasujja N et al (2007) Frequency of and risk factors for HIV dementia in an HIV clinic in sub-Saharan Africa. Neurology 68(5):350–355. https://doi.org/10.1212/01.wnl.0000252811.48891.6d
Wright EJ, Grund B, Robertson K et al (2010) Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons. Neurology 75(10):864–873. https://doi.org/10.1212/WNL.0b013e3181f11bd8
Xiao Q, Guo D, Chen S (2019) Application of CRISPR/Cas9-based gene editing in HIV-1/AIDS therapy. Front Cell Infect Microbiol 9:69. https://doi.org/10.3389/fcimb.2019.00069
Yin C, Zhang T, Qu X et al (2017) In vivo excision of HIV-1 provirus by saCas9 and multiplex single-guide RNAs in animal models. Mol Ther 25(5):1168–1186. https://doi.org/10.1016/j.ymthe.2017.03.012
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Kompella, S. et al. (2020). HIV-Associated Neurocognitive Disorder (HAND): Relative Risk Factors. In: Cysique, L.A., Rourke, S.B. (eds) Neurocognitive Complications of HIV-Infection. Current Topics in Behavioral Neurosciences, vol 50. Springer, Cham. https://doi.org/10.1007/7854_2020_131
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