Generic placeholder image

Current HIV Research

Author(s): Daniela Marić*, Snežana Brkić, Vojislava Bugarski Ignjatović, Željka Nikolaševic, Dalibor Ilić, Miloš Vujanović, Zorka Drvendžija and Biljana Srdić Galić

DOI: 10.2174/1570162X18666200227114310

DownloadDownload PDF Flyer Cite As
Relation of Steatosis to Neurocognitive Function in People Living with HIV

Page: [172 - 180] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: In HIV negative population metabolic syndrome and steatosis are related to poorer neurocognitive (NC) performance. We investigated if similar relation exists in people living with HIV (PLWH).

Methods: We included male PLWH aged 20-65, with undetectable viral load for at least 6 months. Data on levels of education, anthropometric measurements, CD4 levels, ART, markers of metabolic syndrome, smoking and concurrent treatment were collected from database. Concentrations of TNF-α and IL-6 were measured. An ultrasound was used to establish the presence of steatosis, visceral fat thickness and carotid intima media thickness. An extensive NC assessment was done by an experienced neuropsychologist. Cognitive domains were defined as executive functions, divergent reasoning, visuo-constructional abilities, delayed recall and working memory and learning and were measured using a battery of 12 tests.

Results: 88 PLWH were included (mean age 39,9 years), 51% on PIs, 46% on NNRTI; 20,4% had metabolic syndrome, 42% patients had steatosis. Weak but statistically significant negative correlations were found between the presence of metabolic syndrome, steatosis and VFT and cognitive domains (divergent reasoning, delayed recall and working memory). Poorer perfomrance in the domains of divergent reasoning and in the working memory were found in participants with steatosis (p=0,048 and 0,033 respectively).

Conclusion: Although the sample size was relatively small, our results show consistent correlations between the observed neurocognitive variables and metabolic parameters. As central obesity is one of the contributors to NCI, it would be one of the modifiable factors to prevent further neurocognitive decline.

Keywords: steatosis, neurocognition, metabolic syndrome, central obesity, PLWH.

Graphical Abstract

[1]
Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet 2013; 382(9903): 1525-33.
[http://dx.doi.org/10.1016/S0140-6736(13)61809-7] [PMID: 24152939]
[2]
Deeks SG, Tracy R, Douek DC. Systemic effects of inflammation on health during chronic HIV infection. Immunity 2013; 39(4): 633-45.
[http://dx.doi.org/10.1016/j.immuni.2013.10.001] [PMID: 24138880]
[3]
Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 2011; 53(11): 1120-6.
[http://dx.doi.org/10.1093/cid/cir627] [PMID: 21998278]
[4]
Morgan E, Taylor HE, Ryan DT, D’Aquila R, Mustanski B. Systemic inflammation is elevated among both HIV-uninfected and HIV-infected young MSM. AIDS 2019; 33(4): 757-9.
[http://dx.doi.org/10.1097/QAD.0000000000002093] [PMID: 30531319]
[5]
Dinh DM, Volpe GE, Duffalo C, et al. Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. J Infect Dis 2015; 211(1): 19-27.
[http://dx.doi.org/10.1093/infdis/jiu409] [PMID: 25057045]
[6]
Lake JE, Currier JS. Metabolic disease in HIV infection. Lancet Infect Dis 2013; 13(11): 964-75.
[http://dx.doi.org/10.1016/S1473-3099(13)70271-8] [PMID: 24156897]
[7]
Clifford DB, Ances BM. HIV-associated neurocognitive disorder. Lancet Infect Dis 2013; 13(11): 976-86.
[http://dx.doi.org/10.1016/S1473-3099(13)70269-X] [PMID: 24156898]
[8]
Saylor D, Dickens AM, Sacktor N, et al. HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat Rev Neurol 2016; 12(4): 234-48.
[http://dx.doi.org/10.1038/nrneurol.2016.27] [PMID: 26965674]
[9]
Amorosa V, Synnestvedt M, Gross R, et al. A tale of 2 epidemics: the intersection between obesity and HIV infection in Philadelphia. J Acquir Immune Defic Syndr 2005; 39(5): 557-61.
[PMID: 16044007]
[10]
Crum-Cianflone N, Roediger MP, Eberly L, et al. Increasing rates of obesity among HIV-infected persons during the HIV epidemic. PLoS One 2010; 5(4) e10106
[http://dx.doi.org/10.1371/journal.pone.0010106] [PMID: 20419086]
[11]
Nduka CU, Uthman OA, Kimani PK, Stranges S. Body fat changes in people living with HIV on antiretroviral therapy. AIDS Rev 2016; 18(4): 198-211.
[PMID: 27438580]
[12]
Lakey W, Yang LY, Yancy W, Chow SC, Hicks C. Short communication: from wasting to obesity: initial antiretroviral therapy and weight gain in HIV-infected persons. AIDS Res Hum Retroviruses 2013; 29(3): 435-40.
[http://dx.doi.org/10.1089/aid.2012.0234] [PMID: 23072344]
[13]
Koethe JR, Jenkins CA, Lau B, et al. Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS Res Hum Retroviruses 2016; 32(1): 50-8.
[http://dx.doi.org/10.1089/aid.2015.0147] [PMID: 26352511]
[14]
Boodram B, Plankey MW, Cox C, et al. Prevalence and correlates of elevated body mass index among HIV-positive and HIV-negative women in the Women’s Interagency HIV Study. AIDS Patient Care STDS 2009; 23(12): 1009-16.
[http://dx.doi.org/10.1089/apc.2009.0175] [PMID: 19909168]
[15]
Grant PM, Kitch D, McComsey GA, et al. Long-term body composition changes in antiretroviral-treated HIV-infected individuals. AIDS 2016; 30(18): 2805-13.
[http://dx.doi.org/10.1097/QAD.0000000000001248] [PMID: 27662545]
[16]
Crum-Cianflone NF, Roediger M, Eberly LE, et al. Obesity among HIV-infected persons: impact of weight on CD4 cell count. AIDS 2010; 24(7): 1069-72.
[http://dx.doi.org/10.1097/QAD.0b013e328337fe01] [PMID: 20216300]
[17]
Hendricks KM, Willis K, Houser R, Jones CY. Obesity in HIV-infection: dietary correlates. J Am Coll Nutr 2006; 25(4): 321-31.
[http://dx.doi.org/10.1080/07315724.2006.10719542] [PMID: 16943454]
[18]
Jones CY, Hogan JW, Snyder B, et al. Overweight and human immunodeficiency virus (HIV) progression in women: associations HIV disease progression and changes in body mass index in women in the HIV epidemiology research study cohort. Clin Infect Dis 2003; 37(2)(Suppl. 2): S69-80.
[http://dx.doi.org/10.1086/375889] [PMID: 12942377]
[19]
Shuter J, Chang CJ, Klein RS. Prevalence and predictive value of overweight in an urban HIV care clinic. J Acquir Immune Defic Syndr 2001; 26(3): 291-7.
[http://dx.doi.org/10.1097/00126334-200103010-00013] [PMID: 11242203]
[20]
De La Garza R, Rodrigo H, Fernandez F, Roy U. The Increase of HIV-1 infection, neurocognitive impairment, and type 2 diabetes in the Rio Grande Valley. Curr HIV Res 2019; 17(6): 377-87.
[http://dx.doi.org/10.2174/1570162X17666191029162235] [PMID: 31663481]
[21]
d’Arminio Monforte A, Diaz-Cuervo H, De Luca A, et al. Evolution of major non-HIV-related comorbidities in HIV-infected patients in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) Foundation Study cohort in the period 2004-2014. HIV Med 2019; 20(2): 99-109.
[http://dx.doi.org/10.1111/hiv.12683] [PMID: 30461158]
[22]
Nguyen JC, Killcross AS, Jenkins TA. Obesity and cognitive decline: role of inflammation and vascular changes. Front Neurosci 2014; 8: 375.
[http://dx.doi.org/10.3389/fnins.2014.00375] [PMID: 25477778]
[23]
Miller AA, Spencer SJ. Obesity and neuroinflammation: a pathway to cognitive impairment. Brain Behav Immun 2014; 42: 10-21.
[http://dx.doi.org/10.1016/j.bbi.2014.04.001] [PMID: 24727365]
[24]
Boitard C, Parkes SL, Cavaroc A, et al. Switching adolescent high-fat diet to adult control diet restores neurocognitive alterations. Front Behav Neurosci 2016; 10: 225.
[http://dx.doi.org/10.3389/fnbeh.2016.00225] [PMID: 27917115]
[25]
Jagust W, Harvey D, Mungas D, Haan M. Central obesity and the aging brain. Arch Neurol 2005; 62(10): 1545-8.
[http://dx.doi.org/10.1001/archneur.62.10.1545] [PMID: 16216937]
[26]
Heaton RK, Clifford DB, Franklin DR Jr, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 2010; 75(23): 2087-96.
[http://dx.doi.org/10.1212/WNL.0b013e318200d727] [PMID: 21135382]
[27]
Zayyad Z, Spudich S. Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND). Curr HIV/AIDS Rep 2015; 12(1): 16-24.
[http://dx.doi.org/10.1007/s11904-014-0255-3] [PMID: 25604237]
[28]
Heaton RK, Franklin DR, Ellis RJ, 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.
[http://dx.doi.org/10.1007/s13365-010-0006-1] [PMID: 21174240]
[29]
Simioni S, Cavassini M, Annoni JM, et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 2010; 24(9): 1243-50.
[PMID: 19996937]
[30]
Robertson KR, Smurzynski M, Parsons TD, et al. The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 2007; 21(14): 1915-21.
[http://dx.doi.org/10.1097/QAD.0b013e32828e4e27] [PMID: 17721099]
[31]
Grant I, Franklin DR Jr, Deutsch R, et al. Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology 2014; 82(23): 2055-62.
[http://dx.doi.org/10.1212/WNL.0000000000000492] [PMID: 24814848]
[32]
Marra CM, Zhao Y, Clifford DB, et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 2009; 23(11): 1359-66.
[http://dx.doi.org/10.1097/QAD.0b013e32832c4152] [PMID: 19424052]
[33]
Harezlak J, Buchthal S, Taylor M, et al. Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 2011; 25(5): 625-33.
[http://dx.doi.org/10.1097/QAD.0b013e3283427da7] [PMID: 21297425]
[34]
Smith LK, Kuhn TB, Chen J, Bamburg JR. HIV associated neurodegenerative disorders: a new perspective on the role of lipid rafts in Gp120-mediated neurotoxicity. Curr HIV Res 2018; 16(4): 258-69.
[http://dx.doi.org/10.2174/1570162X16666181003144740] [PMID: 30280668]
[35]
McCutchan JA, Marquie-Beck JA, Fitzsimons CA, et al. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology 2012; 78(7): 485-92.
[http://dx.doi.org/10.1212/WNL.0b013e3182478d64] [PMID: 22330412]
[36]
Tchelepi H, Ralls PW, Radin R, Grant E. Sonography of diffuse liver disease. J Ultrasound Med 2002; 21(9): 1023-32.
[http://dx.doi.org/10.7863/jum.2002.21.9.1023] [PMID: 12216750]
[37]
Heaton R. A Manual for the Wisconsin Card Sorting Test Psychological Assessment Resources. Odessa, Florida 1981.
[38]
Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958; 8(3): 271-6.
[http://dx.doi.org/10.2466/pms.1958.8.3.271]
[39]
Selnes OA. A compendium of neuropsychological tests: Administration, norms, and commentary. Neurology 1991; 41(11): 1856-7.
[http://dx.doi.org/10.1212/WNL.41.11.1856-a]
[40]
Pavlović DM. Diagnostic Tests in Neuropsychology. 2nd Ed.. Belgrade, Serbia: Grafos-Beograd 2003.
[41]
Goodglass H, Kaplan E. The assessment of aphasia and related disorders. 2nd ed. Philadelphia, PA: Lea & Febiger 1983.
[42]
Lezak MD. Neuropsychological assessment. 3rd ed. New York, NY: Oxford University Press 1995.
[43]
Osterrieth PA. Test of copying a complex figure: A contribution to the study of perception and memory. Arch Psychol 1944; 30: 286-356.
[44]
Rey A. The psychological examination in cases of traumatic encephalopathy. Arch Psychol 1941; 28: 286-340.
[45]
Rey A. Clinical Tests in Psychology. Paris, France: Presses Universitaires de France 1964.
[46]
Wechsler D. Wechsler memory scale-revised. Psychological Corporation 1987.
[47]
Yaffe K, Haan M, Blackwell T, Cherkasova E, Whitmer RA, West N. Metabolic syndrome and cognitive decline in elderly Latinos: findings from the Sacramento Area Latino Study of Aging study. J Am Geriatr Soc 2007; 55(5): 758-62.
[http://dx.doi.org/10.1111/j.1532-5415.2007.01139.x] [PMID: 17493197]
[48]
Panza F, Solfrizzi V, Logroscino G, et al. Current epidemiological approaches to the metabolic-cognitive syndrome. J Alzheimers Dis 2012; 30(Suppl. 2): S31-75.
[http://dx.doi.org/10.3233/JAD-2012-111496] [PMID: 22561330]
[49]
Solfrizzi V, Scafato E, Capurso C, et al. Metabolic syndrome, mild cognitive impairment, and progression to dementia. Neurobiol Aging 2011; 32(11): 1932-41.
[http://dx.doi.org/10.1016/j.neurobiolaging.2009.12.012] [PMID: 20045217]
[50]
Prickett C, Brennan L, Stolwyk R. Examining the relationship between obesity and cognitive function: a systematic literature review. Obes Res Clin Pract 2015; 9(2): 93-113.
[http://dx.doi.org/10.1016/j.orcp.2014.05.001] [PMID: 25890426]
[51]
Carnell S, Gibson C, Benson L, Ochner CN, Geliebter A. Neuroimaging and obesity: current knowledge and future directions. Obes Rev 2012; 13(1): 43-56.
[http://dx.doi.org/10.1111/j.1467-789X.2011.00927.x] [PMID: 21902800]
[52]
Hargrave SL, Jones S, Davidson TL. The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction. Curr Opin Behav Sci 2016; 9: 40-6.
[http://dx.doi.org/10.1016/j.cobeha.2015.12.001] [PMID: 26998507]
[53]
Ho AJ, Raji CA, Becker JT, et al. Obesity is linked with lower brain volume in 700 AD and MCI patients. Neurobiol Aging 2010; 31(8): 1326-39.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.04.006] [PMID: 20570405]
[54]
Raji CA, Ho AJ, Parikshak NN, et al. Brain structure and obesity. Hum Brain Mapp 2010; 31(3): 353-64.
[PMID: 19662657]
[55]
Anstey KJ, Cherbuin N, Budge M, Young J. Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev 2011; 12(5): e426-37.
[http://dx.doi.org/10.1111/j.1467-789X.2010.00825.x] [PMID: 21348917]
[56]
Pasha EP, Birdsill A, Parker P, Elmenshawy A, Tanaka H, Haley AP. Visceral adiposity predicts subclinical white matter hyperintensities in middle-aged adults. Obes Res Clin Pract 2017; 11(2): 177-87.
[http://dx.doi.org/10.1016/j.orcp.2016.04.003] [PMID: 27133528]
[57]
Smith E, Hay P, Campbell L, Trollor JN. A review of the association between obesity and cognitive function across the lifespan: implications for novel approaches to prevention and treatment. Obes Rev 2011; 12(9): 740-55.
[http://dx.doi.org/10.1111/j.1467-789X.2011.00920.x] [PMID: 21991597]
[58]
Yates KF, Sweat V, Yau PL, Turchiano MM, Convit A. Impact of metabolic syndrome on cognition and brain: a selected review of the literature. Arterioscler Thromb Vasc Biol 2012; 32(9): 2060-7.
[http://dx.doi.org/10.1161/ATVBAHA.112.252759] [PMID: 22895667]
[59]
Willeit P, Thompson SG, Agewall S, et al. Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. Eur J Prev Cardiol 2016; 23(2): 194-205.
[http://dx.doi.org/10.1177/2047487314560664] [PMID: 25416041]
[60]
Oni ET, Agatston AS, Blaha MJ, et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis 2013; 230(2): 258-67.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.07.052] [PMID: 24075754]
[61]
Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications. J Hepatol 2016; 65(2): 425-43.
[http://dx.doi.org/10.1016/j.jhep.2016.04.005] [PMID: 27091791]
[62]
Beraldo RA, Meliscki GC, Silva BR, et al. Anthropometric measures of central adiposity are highly concordant with predictors of cardiovascular disease risk in HIV patients. Am J Clin Nutr 2018; 107(6): 883-93.
[http://dx.doi.org/10.1093/ajcn/nqy049] [PMID: 29868914]
[63]
Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005; 352(1): 48-62.
[http://dx.doi.org/10.1056/NEJMra041811] [PMID: 15635112]
[64]
Stanley TL, Grinspoon SK. Body composition and metabolic changes in HIV-infected patients. J Infect Dis 2012; 205(suppl_3): S383-90.
[65]
Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA 2015; 313(22): 2263-73.
[http://dx.doi.org/10.1001/jama.2015.5370] [PMID: 26057287]
[66]
Shah RV, Murthy VL, Abbasi SA, et al. Visceral adiposity and the risk of metabolic syndrome across body mass index: the MESA Study. JACC Cardiovasc Imaging 2014; 7(12): 1221-35.
[http://dx.doi.org/10.1016/j.jcmg.2014.07.017] [PMID: 25440591]
[67]
Dieguez S, Staub F, Bruggimann L, Bogousslavsky J. Is poststroke depression a vascular depression? J Neurol Sci 2004; 226(1-2): 53-8.
[http://dx.doi.org/10.1016/j.jns.2004.09.012] [PMID: 15537520]
[68]
Archibald SL, Masliah E, Fennema-Notestine C, et al. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss. Arch Neurol 2004; 61(3): 369-76.
[http://dx.doi.org/10.1001/archneur.61.3.369] [PMID: 15023814]
[69]
Khov N, Sharma A, Riley TR. Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20(22): 6821-5.
[http://dx.doi.org/10.3748/wjg.v20.i22.6821] [PMID: 24944472]
[70]
Mellinger JL, Pencina KM, Massaro JM, et al. Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study. J Hepatol 2015; 63(2): 470-6.
[http://dx.doi.org/10.1016/j.jhep.2015.02.045] [PMID: 25776891]
[71]
Androutsakos T, Schina M, Pouliakis A, Kontos A, Sipsas N, Hatzis G. Liver fibrosis assessment in a cohort of greek hiv mono-infected patients by non-invasive biomarkers. Curr HIV Res 2019; 17(3): 173-82.
[http://dx.doi.org/10.2174/1570162X17666190809153245] [PMID: 31549590]
[72]
Jaruvongvanich V, Wirunsawanya K, Sanguankeo A, Upala S. Nonalcoholic fatty liver disease is associated with coronary artery calcification: A systematic review and meta-analysis. Dig Liver Dis 2016; 48(12): 1410-7.
[http://dx.doi.org/10.1016/j.dld.2016.09.002] [PMID: 27697419]
[73]
Seo SW, Gottesman RF, Clark JM, et al. Nonalcoholic fatty liver disease is associated with cognitive function in adults. Neurology 2016; 86(12): 1136-42.
[http://dx.doi.org/10.1212/WNL.0000000000002498] [PMID: 26911638]
[74]
Weinstein AA, de Avila L, Paik J, et al. Cognitive performance in individuals with non-alcoholic fatty liver disease and/or type 2 diabetes mellitus. Psychosomatics 2018; 59(6): 567-74.
[http://dx.doi.org/10.1016/j.psym.2018.06.001] [PMID: 30086995]
[75]
Filipović B, Marković O, Đurić V, Filipović B. Cognitive changes and brain volume reduction in patients with nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol 2018; 2018: 1-6.
[http://dx.doi.org/10.1155/2018/9638797]
[76]
Takahashi A, Kono S, Wada A, et al. Reduced brain activity in female patients with non-alcoholic fatty liver disease as measured by near-infrared spectroscopy. PLoS One 2017; 12(4) e0174169
[http://dx.doi.org/10.1371/journal.pone.0174169] [PMID: 28376101]
[77]
Weinstein G, Zelber-Sagi S, Preis SR, et al. Association of nonalcoholic fatty liver disease with lower brain volume in healthy middle-aged adults in the Framingham study. JAMA Neurol 2018; 75(1): 97-104.
[http://dx.doi.org/10.1001/jamaneurol.2017.3229] [PMID: 29159396]
[78]
Grima P, Fabbiani M, Mondi A, et al. High Grade Liver Steatosis and Cognitive Impairment in HIV+ Patients. Top Antivir Med 2013; 21(3): 102-10.