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Greater Than Age-Related Changes in Brain Diffusion of HIV Patients After 1 Year

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Abstract

Chronic infection with HIV is associated with neuroinflammation. Prior diffusion tensor imaging (DTI) studies demonstrated increased mean diffusion (MD) and decreased fractional anisotropy (FA) in the white matter (WM) and subcortical brain regions of HIV patients. The current study aims to detect whether there are greater than age-related brain changes in HIV patients after a 1-year follow-up period using DTI. Thirty-nine antiretroviral-stable HIV subjects and 32 HIV-seronegative (SN) controls were evaluated, with neuropsychological tests and DTI, at baseline and after 1 year. MD and FA in the genu and splenium of the corpus callosum and in six other subcortical and white matter regions were evaluated bilaterally. Compared to SN controls, HIV subjects had significantly higher MD in the frontal WM (p = 0.0104) and lower FA in the parietal WM (p = 0.006). After 1 year, HIV subjects showed increase in MD in frontal and parietal WM, putamen, and genu; HIV subjects also showed greater increased genu diffusion than SN controls (p = 0.005). Changes in global cognitive deficit score correlated with changes in MD in the genu and FA in the parietal and frontal WM and putamen (multiple regression, p = 0.0008). Lastly, normal age-dependent changes in frontal WM diffusion and FA in genu and putamen were not observed in HIV subjects. Since increased MD may reflect increased neuroinflammation, our findings suggest greater than normal age-related inflammatory changes in the genu of these HIV patients, which may contribute to the cognitive deficits. Measurements of MD in the genu may be useful for monitoring disease progression in HIV brain infection.

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References

  • Adamson DC, Wildemann B, Sasaki M, Glass JD, McArthur JC, Christov VI et al (1996) Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 274:1917–1921 doi:10.1126/science.274.5294.1917

    Article  PubMed  CAS  Google Scholar 

  • Banks WA, Ercal N, Price TO (2006) The blood–brain barrier in neuroAIDS. Curr HIV Res 4:259–266 doi:10.2174/157016206777709447

    Article  PubMed  CAS  Google Scholar 

  • Bartzokis G, Tishler TA, Lu PH, Villablanca P, Altshuler LL, Carter M et al (2007) Brain ferritin iron may influence age- and gender-related risks of neurodegeneration. Neurobiol Aging 28:414–423 doi:10.1016/j.neurobiolaging.2006.02.005

    Article  PubMed  CAS  Google Scholar 

  • Benedict RH, Bruce J, Dwyer MG, Weinstock-Guttman B, Tjoa C, Tavazzi E et al (2007) Diffusion-weighted imaging predicts cognitive impairment in multiple sclerosis. Mult Scler 13:722–730 doi:10.1177/1352458507075592

    Article  PubMed  Google Scholar 

  • Blair J, Spreen O (1989) The new adult reading test—Revised manual. University of Victoria, Vol Victoria, Canada

    Google Scholar 

  • Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15:289–298 doi:10.1159/000111347

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Leonido-Yee M, Walot I, Singer E (1999a) Cerebral metabolite abnormalities correlate with clinical severity of HIV-cognitive motor complex. Neurology 52:100–108

    PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Leonido-Yee M, Witt M, Speck O, Walot I et al (1999b) Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 53:782–789

    PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Witt M, Ames N, Jocivich J, Speck O et al (2002) Relationships among cerebral metabolites, cognitive function and viral loads in antiretroviral-naïve HIV patients. Neuroimage 17:1638–1648 doi:10.1006/nimg.2002.1254

    Article  PubMed  Google Scholar 

  • Chang L, Tomasi D, Yakupov R, Lozar C, Arnold S, Caparelli E et al (2004) Adaptation of the attention network in human immunodeficiency virus brain injury. Ann Neurol 56:259–272 doi:10.1002/ana.20190

    Article  PubMed  Google Scholar 

  • Chang L, Ernst T, Speck O, Grob C (2005) Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities. Am J Psychiatry 162:361–369 doi:10.1176/appi.ajp.162.2.361

    Article  PubMed  Google Scholar 

  • Chen ZG, Li TQ, Hindmarsh T (2001) Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique. A methodological study of the aging brain. Acta Radiol 42:447–458 doi:10.1034/j.1600-0455.2001.420504.x

    Article  PubMed  CAS  Google Scholar 

  • Cloak CC, Chang L, Ernst T (2004) Increased frontal white matter diffusion is associated with glial metabolites and psychomotor slowing in HIV. J Neuroimmunol 157:147–152 doi:10.1016/j.jneuroim.2004.08.043

    Article  PubMed  CAS  Google Scholar 

  • Conant K, St Hillaire C, Anderson C, Galey D, Wang J, Nath A (2004) Human immunodeficiency virus type 1 Tat and methamphetamine affect the release and activation of matrix-degrading proteinases. J Neurovirol 10:21–28 doi:10.1080/13550280490261699

    Article  PubMed  CAS  Google Scholar 

  • Connolly NC, Riddler SA, Rinaldo CR (2005) Proinflammatory cytokines in HIV disease—a review and rationale for new therapeutic approaches. AIDS Rev 7:168–180

    PubMed  Google Scholar 

  • Dik MG, Jonker C, Hack CE, Smit JH, Comijs HC, Eikelenboom P (2005) Serum inflammatory proteins and cognitive decline in older persons. Neurology 64:1371–1377

    PubMed  CAS  Google Scholar 

  • El-Hage N, Wu G, Wang J, Ambati J, Knapp PE, Reed JL et al (2006) HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokines. Glia 53:132–146 doi:10.1002/glia.20262

    Article  PubMed  Google Scholar 

  • Ernst T, Chang L, Arnold S (2003) Increased glial markers predict increased working memory network activation in HIV patients. Neuroimage 19:1686–1693 doi:10.1016/S1053-8119(03)00232-5

    Article  PubMed  CAS  Google Scholar 

  • Filippi C, Ulug A, Ryan E, Ferrando S, van Gorp W (2001) Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. Am J Neuroradiol 22:277–283

    PubMed  CAS  Google Scholar 

  • Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198 doi:10.1016/0022-3956(75)90026-6

    Article  PubMed  CAS  Google Scholar 

  • Gemma C, Bickford PC (2007) Interleukin-1beta and caspase-1: players in the regulation of age-related cognitive dysfunction. Rev Neurosci 18:137–148

    PubMed  CAS  Google Scholar 

  • Hallgren B, Sourander P (1958) The effect of age on the non-haemin iron in the human brain. J Neurochem 3:41–51 doi:10.1111/j.1471-4159.1958.tb12607.x

    Article  PubMed  CAS  Google Scholar 

  • Hauser KF, El-Hage N, Stiene-Martin A, Maragos WF, Nath A, Persidsky Y et al (2007) HIV-1 neuropathogenesis: glial mechanisms revealed through substance abuse. J Neurochem 100:567–586 doi:10.1111/j.1471-4159.2006.04227.x

    Article  PubMed  CAS  Google Scholar 

  • Jernigan T, Gamst A, Archibald S, Fennema-Notestine C, Mindt M, Marcotte T et al (2005) Effects of methamphetamine dependence and HIV infection on cerebral morphology. Am J Psychiatry 162:1461–1472 doi:10.1176/appi.ajp.162.8.1461

    Article  PubMed  Google Scholar 

  • Jiang H, van Zijl PC, Kim J, Pearlson GD, Mori S (2006) DtiStudio: resource program for diffusion tensor computation and fiber bundle tracking. Comput Methods Programs Biomed 81:106–116 doi:10.1016/j.cmpb.2005.08.004

    Article  PubMed  Google Scholar 

  • Kraus MF, Susmaras T, Caughlin BP, Walker CJ, Sweeney JA, Little DM (2007) White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain 130:2508–2519 doi:10.1093/brain/awm216

    Article  PubMed  Google Scholar 

  • Laubenberger J, Haussinger D, Bayer S, Thielemann S, Schneider B, Mundinger A et al (1996) HIV-related metabolic abnormalities in the brain: Depiction with proton MR spectroscopy with short echo times. Radiology 199:805–810

    PubMed  CAS  Google Scholar 

  • Nath A (2002) Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. J Infect Dis 186(Suppl 2):S193–S198 doi:10.1086/344528

    Article  PubMed  CAS  Google Scholar 

  • Paul RH, Yiannoutsos CT, Miller EN, Chang L, Marra CM, Schifitto G et al (2007) Proton MRS and neuropsychological correlates in AIDS dementia complex: evidence of subcortical specificity. J Neuropsychiatry Clin Neurosci 19(3):283–292 doi:10.1176/appi.neuropsych.19.3.283

    PubMed  Google Scholar 

  • Pfefferbaum A, Adalsteinsson E, Rohlfing T, Sullivan EV (2008) Diffusion tensor imaging of deep gray matter brain structures: Effects of age and iron concentration. Neurobiol Aging (May 28, Epub ahead of print)

  • Pfefferbaum A, Sullivan EV, Hedehus M, Lim KO, Adalsteinsson E, Moseley M (2000) Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging. Magn Reson Med 44:259–268 doi:10.1002/1522-2594(200008)44:2<259::AID-MRM13>3.0.CO;2-6

    Article  PubMed  CAS  Google Scholar 

  • Pfefferbaum A, Rosenbloom MJ, Adalsteinsson E, Sullivan EV (2007) Diffusion tensor imaging with quantitative fibre tracking in HIV infection and alcoholism comorbidity: synergistic white matter damage. Brain 130:48–64 doi:10.1093/brain/awl242

    Article  PubMed  Google Scholar 

  • Pomara N, Crandall D, Choi S, Johnson G, Lim K (2001) White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study. Psychiatry Res 106:15–24 doi:10.1016/S0925-4927(00)00082-2

    Article  PubMed  CAS  Google Scholar 

  • Power C, Johnson RT (1995) HIV-1 associated dementia: clinical features and pathogenesis. Can J Neurol Sci 22:92–100

    PubMed  CAS  Google Scholar 

  • Radloff LL (1977) The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401 doi:10.1177/014662167700100306

    Article  Google Scholar 

  • Ragin AB, Wu Y, Storey P, Cohen BA, Edelman RR, Epstein LG (2005) Diffusion tensor imaging of subcortical brain injury in patients infected with human immunodeficiency virus. J Neurovirol 11:292–298 doi:10.1080/13550280590953799

    Article  PubMed  Google Scholar 

  • Ragin AB, Wu Y, Storey P, Cohen BA, Edelman RR, Epstein LG (2006) Monocyte chemoattractant protein-1 correlates with subcortical brain injury in HIV infection. Neurology 66:1255–1257 doi:10.1212/01.wnl.0000208433.34723.65

    Article  PubMed  CAS  Google Scholar 

  • Raz N, Rodrigue KM, Kennedy KM, Head D, Gunning-Dixon F, Acker JD (2003) Differential aging of the human striatum: longitudinal evidence. Am J Neuroradiol 24:1849–1856

    PubMed  Google Scholar 

  • Simes RJ (1986) An improved Bonferroni procedure for multiple tests of significance. Biometrika 73:751–754 doi:10.1093/biomet/73.3.751

    Article  Google Scholar 

  • Steiner J, Haughey N, Li W, Venkatesan A, Anderson C, Reid R et al (2006) Oxidative stress and therapeutic approaches in HIV dementia. Antioxid Redox Signal 8:2089–2100 doi:10.1089/ars.2006.8.2089

    Article  PubMed  CAS  Google Scholar 

  • Sullivan E, Pfefferbaum A (2003) Diffusion tensor imaging in normal aging and neuropsychiatric disorders. Eur J Radiol 45:244–255 doi:10.1016/S0720-048X(02)00313-3

    Article  PubMed  Google Scholar 

  • Thurnher MM, Castillo M, Stadler A, Rieger A, Schmid B, Sundgren PC (2005) Diffusion-tensor MR imaging of the brain in human immunodeficiency virus-positive patients. Am J Neuroradiol 26:2275–2281

    PubMed  Google Scholar 

  • Woods SP, Rippeth JD, Frol AB, Levy JK, Ryan E, Soukup VM et al (2004) Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV. J Clin Exp Neuropsychol 26:759–778

    Article  PubMed  Google Scholar 

  • Wu Y, Storey P, Cohen BA, Epstein LG, Edelman RR, Ragin AB (2006) Diffusion alterations in corpus callosum of patients with HIV. Am J Neuroradiol 27:656–660

    PubMed  CAS  Google Scholar 

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Acknowledgements

We thank our research participants and support by the NIH (2R01MH61427; K24-DA16170; K02-DA16991; 5P20-RR11091; G12-RR003061) and the Office of National Drug Control Policy (ONDCP). We also thank Kenneth Yue, PhD; Daniel Alicata, MD, PhD; Renat Yakupov, MS; Grace Crocket, BA; and Caroline Jiang, MS, for their assistance in data collection or analyses.

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Dr. Miller is the author and distributor of the CalCAP program and has a financial interest in this software.

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Correspondence to Linda Chang.

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Chang, L., Wong, V., Nakama, H. et al. Greater Than Age-Related Changes in Brain Diffusion of HIV Patients After 1 Year. J Neuroimmune Pharmacol 3, 265–274 (2008). https://doi.org/10.1007/s11481-008-9120-8

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  • DOI: https://doi.org/10.1007/s11481-008-9120-8

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