Skip to main content

Advertisement

Log in

Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Individuals infected with HIV are living longer due to effective treatment with combination antiretroviral therapy (cART). Despite these advances, HIV-associated neurocognitive disorders (HAND) remain prevalent. In this study, we analyzed resting state functional connectivity (rs-fc) data from HIV-infected and matched HIV-uninfected adults aged 60 years and older to determine associations between HIV status, neuropsychological performance, and clinical variables. HIV-infected participants with detectable plasma HIV RNA exhibited decreased rs-fc within the salience (SAL) network compared to HIV-infected participants with suppressed plasma HIV RNA. We did not identify differences in rs-fc within HIV-infected individuals by HAND status. Our analysis identifies focal deficits in the SAL network that may be mitigated with suppression of plasma virus. However, these findings suggest that rs-fc may not be sensitive as a marker of HAND among individuals with suppressed plasma viral loads.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Andrews-Hanna JR, Snyder AZ, Vincent JL, Lustig C, Head D, Raichle ME, Buckner RL (2007) Disruption of large-scale brain systems in advanced aging. Neuron 56(5):924–935

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • 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(18):1789–1799

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Brier MR, Thomas JB, Snyder AZ, Benzinger TL, Zhang D, Raichle ME, Holtzman DM, Morris JC, Ances BM (2012) Loss of intranetwork and internetwork resting state functional connections with Alzheimer’s disease progression. J Neurosci 32(26):8890–8899

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Brier MR, Thomas JB, Snyder AZ, Wang L, Fagan AM, Benzinger T, Morris JC, Ances BM (2014) Unrecognized preclinical Alzheimer disease confounds rs-fcMRI studies of normal aging. Neurology 83(18):1613–1619

    Article  PubMed  PubMed Central  Google Scholar 

  • Brooks JT, Buchacz K, Gebo KA, Mermin J (2012) HIV infection and older Americans: the public health perspective. Am J Public Health 102(8):1516–1526

    Article  PubMed  PubMed Central  Google Scholar 

  • Chiao S, Rosen HJ, Nicolas K, Wendelken LA, Alcantar O, Rankin KP, Miller B, Valcour V (2013) Deficits in self-awareness impact the diagnosis of asymptomatic neurocognitive impairment in HIV. AIDS Res Hum Retrovir 29(6):949–956

    Article  PubMed  PubMed Central  Google Scholar 

  • Clifford DB, Ances BM (2013) HIV-associated neurocognitive disorder. Lancet Infect Dis 13(11):976–986

    Article  PubMed  PubMed Central  Google Scholar 

  • Eden A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B, Price RW, Gisslen M (2010) HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis 202(12):1819–1825

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Geerligs L, Renken RJ, Saliasi E, Maurits NM and Lorist MM (2014) “A brain-wide study of age-related changes in functional connectivity.” Cereb Cortex

  • Glisky EL (2007) Changes in cognitive function in human aging. Brain aging: models, methods, and mechanisms. D. R. Riddle. Boca Raton (FL)

  • Hacker CD, Laumann TO, Szrama NP, Baldassarre A, Snyder AZ, Leuthardt EC, Corbetta M (2013) Resting state network estimation in individual subjects. Neuroimage 82:616–633

    Article  PubMed  PubMed Central  Google Scholar 

  • Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17(1):3–16

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hedden T, Mormino EC, Amariglio RE, Younger AP, Schultz AP, Becker JA, Buckner RL, Johnson KA, Sperling RA, Rentz DM (2012) Cognitive profile of amyloid burden and white matter hyperintensities in cognitively normal older adults. J Neurosci 32(46):16233–16242

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • High KP, Brennan-Ing M, Clifford DB, Cohen MH, Currier J, Deeks SG, Deren S, Effros RB, Gebo K, Goronzy JJ, Justice AC, Landay A, Levin J, Miotti PG, Munk RJ, Nass H, Rinaldo CR Jr, Shlipak MG, Tracy R, Valcour V, Vance DE, Walston JD, Volberding P (2012) “HIV and aging: state of knowledge and areas of critical need for research. A report to the NIH Office of AIDS Research by the HIV and Aging Working Group.”. J Acquir Immune Defic Syndr 60(Suppl 1):S1–18

    Article  PubMed  CAS  Google Scholar 

  • Jahanshad N, Valcour VG, Nir TM, Kohannim O, Busovaca E, Nicolas K and Thompson P (2012). “Disrupted brain networks in the aging HIV+ population.” Brain Connect

  • Kaul M (2009) HIV-1 associated dementia: update on pathological mechanisms and therapeutic approaches. Curr Opin Neurol 22(3):315–320

    Article  PubMed  PubMed Central  Google Scholar 

  • Morgan EE, Iudicello JE, Weber E, Duarte NA, Riggs PK, Delano-Wood L, Ellis R, Grant I, Woods SP (2012) Synergistic effects of HIV infection and older age on daily functioning. J Acquir Immune Defic Syndr 61(3):341–348

    Article  PubMed  PubMed Central  Google Scholar 

  • Nightingale S, Winston A, Letendre S, Michael BD, McArthur JC, Khoo S, Solomon T (2014) Controversies in HIV-associated neurocognitive disorders. Lancet Neurol 13(11):1139–1151

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Nir TM, Jahanshad N, Busovaca E, Wendelken L, Nicolas K, Thompson PM and Valcour VG (2013) “Mapping white matter integrity in elderly people with HIV.” Hum Brain Mapp

  • Ortega M, Brier MR, Ances BM (2015) Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity. AIDS 29(6):703–712

    Article  PubMed  CAS  Google Scholar 

  • Pathai S, Bajillan H, Landay AL, High KP (2014) Is HIV a model of accelerated or accentuated aging? J Gerontol A Biol Sci Med Sci 69(7):833–842

    Article  PubMed  PubMed Central  Google Scholar 

  • Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 59(3):2142–2154

    Article  PubMed  PubMed Central  Google Scholar 

  • Power JD, Mitra A, Laumann TO, Snyder AZ, Schlaggar BL, Petersen SE (2014) Methods to detect, characterize, and remove motion artifact in resting state fMRI. Neuroimage 84:320–341

    Article  PubMed  Google Scholar 

  • Saad ZS, Reynolds RC, Jo HJ, Gotts SJ, Chen G, Martin A, Cox RW (2013) Correcting brain-wide correlation differences in resting-state FMRI. Brain Connect 3(4):339–352

    Article  PubMed  PubMed Central  Google Scholar 

  • Sacktor N, Skolasky R, Selnes OA, Watters M, Poff P, Shiramizu B, Shikuma C, Valcour V (2007) Neuropsychological test profile differences between young and old human immunodeficiency virus-positive individuals. J Neurovirol 13(3):203–209

    Article  PubMed  Google Scholar 

  • Schulte T, Muller-Oehring EM, Sullivan EV, Pfefferbaum A (2011) Disruption of emotion and conflict processing in HIV infection with and without alcoholism comorbidity. J Int Neuropsychol Soc 17(3):537–550

    Article  PubMed  PubMed Central  Google Scholar 

  • Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD (2009) Neurodegenerative diseases target large-scale human brain networks. Neuron 62(1):42–52

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Shulman GL, Pope DL, Astafiev SV, McAvoy MP, Snyder AZ, Corbetta M (2010) Right hemisphere dominance during spatial selective attention and target detection occurs outside the dorsal frontoparietal network. J Neurosci 30(10):3640–3651

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Smyser CD, Inder TE, Shimony JS, Hill JE, Degnan AJ, Snyder AZ, Neil JJ (2010) Longitudinal analysis of neural network development in preterm infants. Cereb Cortex 20(12):2852–2862

    Article  PubMed  PubMed Central  Google Scholar 

  • Thomas JB, Brier MR, Ortega M, Benzinger TL, Ances BM (2015) Weighted brain networks in disease: centrality and entropy in human immunodeficiency virus and aging. Neurobiol Aging 36(1):401–412

    Article  PubMed  PubMed Central  Google Scholar 

  • Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, Suwanwela NC, Jagodzinski L, Michael N, Spudich S, van Griensven F, de Souza M, Kim J, Ananworanich J (2012) “Central nervous system viral invasion and inflammation during acute HIV infection.”. J Infect Dis 206(2):275–282

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Vance DE, Fazeli PL, Gakumo CA (2013) The impact of neuropsychological performance on everyday functioning between older and younger adults with and without HIV. J Assoc Nurses AIDS Care 24(2):112–125

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang L, Roe CM, Snyder AZ, Brier MR, Thomas JB, Xiong C, Benzinger TL, Morris JC, Ances BM (2012) Alzheimer disease family history impacts resting state functional connectivity. Ann Neurol 72(4):571–577

    Article  PubMed  PubMed Central  Google Scholar 

  • Woods SP, Moore DJ, Weber E, Grant I (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19(2):152–168

    Article  PubMed  PubMed Central  Google Scholar 

  • Wright PW, Heaps JM, Shimony JS, Thomas JB, Ances BM (2012) The effects of HIV and combination antiretroviral therapy on white matter integrity. AIDS 26(12):1501–1508

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Yao Y, Lu WL, Xu B, Li CB, Lin CP, Waxman D, Feng JF (2013) The increase of the functional entropy of the human brain with age. Sci Rep 3:2853

    PubMed  CAS  PubMed Central  Google Scholar 

  • Zhang D, Raichle ME (2010) Disease and the brain’s dark energy. Nat Rev Neurol 6(1):15–28

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank our study participants. We also thank Hannah Jang, Robin Ketelle, Katherine Rankin, and Stephanie Chiao for their involvement in the HIV Over 60 Cohort. This work was funded by the National Institute of Health Grants K23-AG032872 (VV), R01-NR012907 (BMA), R01-NR012657 (BMA), and R01-NR014449 (BMA); the Larry L. Hillblom Foundation (VV), the UCSF/GIVI Center For AIDS Research, and the UCSF AIDS Research Institute. Additional support from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131.

Conflict of interest

The authors, Anika Guha BA, Liang Wang MD, Aaron Tanenbaum BS BA, Pardis Esmaeili-Firidouni BS, Lauren A. Wendelken MS, Edgar Busovaca BA, Katherine Clifford BA, Akash Desai BS, Beau M. Ances MD PhD, and Victor Valcour MD PhD, declare that they have no conflict of interest. Dr. Valcour has served as a consultant for ViiV Healthcare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Victor Valcour.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guha, A., Wang, L., Tanenbaum, A. et al. Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60. J. Neurovirol. 22, 80–87 (2016). https://doi.org/10.1007/s13365-015-0370-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-015-0370-y

Keywords

Navigation