Additive and Synergistic Cardiovascular Disease Risk Factors and HIV Disease Markers' Effects on White Matter Microstructure in Virally Suppressed HIV.
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
entrez:
22
7
2020
pubmed:
22
7
2020
medline:
12
3
2021
Statut:
ppublish
Résumé
It is unclear whether intermediate to high cardiovascular disease (CVD) risk and HIV disease status may have additive (ie, independent statistical effects concomitantly tested) or synergistic effects on white matter microstructure and cognition in virally suppressed HIV-infected (HIV+) men relative to sex and age-matched controls. Tertiary health care observational cohort. Eighty-two HIV+ men (mean age 55 ± 6 years, 10%-30% on various CVD drugs; 20% with previous CVD) and 40 HIV-uninfected (HIV-) men (none with previous CVD; 10%-20% on various CVD drugs) underwent diffusion tensor imaging and neuropsychological testing. A standard classification of intermediate to high CVD risk (CVD+ group) was based on the Framingham score ≥15% cutoff and/or a history of CVD. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified in 11 white matter tracts. Within the HIV- group, the CVD+ group had lower FA (P = 0.03) and higher MD (P = 0.003) in the corona radiata and higher MD in the corpus callosum (P = 0.02) and superior fasciculi (P = 0.03) than the CVD- group. Within the HIV+ group, the CVD+ group had lower FA in the superior fasciculi (P = 0.04) and higher MD in the uncinate fasciculus (P = 0.04), and lower FA (P = 0.01) and higher MD (P = 0.03) in the fornix than the CVD- group. The fornix alterations were also abnormal compared with the HIV- groups. The HIV+ CVD+ was more likely to have HIV-associated dementia. Older age, antihypertensive use, longer HIV duration, and higher C-reactive protein associated with lower FA and higher MD. Higher blood CD4 lymphocyte count and CD4/CD8 ratio associated with higher FA and lower MD. In virally suppressed HIV, CVD risk factors have a mostly additive contribution to white matter microstructural alterations, leading to a different distribution of injury in HIV- and HIV+ persons with CVD. There was also evidence of a synergistic effect of CVD and HIV factors on the fornix white matter injury.
Sections du résumé
BACKGROUND
It is unclear whether intermediate to high cardiovascular disease (CVD) risk and HIV disease status may have additive (ie, independent statistical effects concomitantly tested) or synergistic effects on white matter microstructure and cognition in virally suppressed HIV-infected (HIV+) men relative to sex and age-matched controls.
SETTING
Tertiary health care observational cohort.
METHODS
Eighty-two HIV+ men (mean age 55 ± 6 years, 10%-30% on various CVD drugs; 20% with previous CVD) and 40 HIV-uninfected (HIV-) men (none with previous CVD; 10%-20% on various CVD drugs) underwent diffusion tensor imaging and neuropsychological testing. A standard classification of intermediate to high CVD risk (CVD+ group) was based on the Framingham score ≥15% cutoff and/or a history of CVD. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified in 11 white matter tracts.
RESULTS
Within the HIV- group, the CVD+ group had lower FA (P = 0.03) and higher MD (P = 0.003) in the corona radiata and higher MD in the corpus callosum (P = 0.02) and superior fasciculi (P = 0.03) than the CVD- group. Within the HIV+ group, the CVD+ group had lower FA in the superior fasciculi (P = 0.04) and higher MD in the uncinate fasciculus (P = 0.04), and lower FA (P = 0.01) and higher MD (P = 0.03) in the fornix than the CVD- group. The fornix alterations were also abnormal compared with the HIV- groups. The HIV+ CVD+ was more likely to have HIV-associated dementia. Older age, antihypertensive use, longer HIV duration, and higher C-reactive protein associated with lower FA and higher MD. Higher blood CD4 lymphocyte count and CD4/CD8 ratio associated with higher FA and lower MD.
CONCLUSIONS
In virally suppressed HIV, CVD risk factors have a mostly additive contribution to white matter microstructural alterations, leading to a different distribution of injury in HIV- and HIV+ persons with CVD. There was also evidence of a synergistic effect of CVD and HIV factors on the fornix white matter injury.
Identifiants
pubmed: 32692114
doi: 10.1097/QAI.0000000000002390
pii: 00126334-202008150-00014
doi:
Substances chimiques
Anti-HIV Agents
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
543-551Références
Teeraananchai S, Kerr S, Amin J, et al. Life expectancy of HIV-positive people after starting combination antiretroviral therapy: a meta-analysis. HIV Med. 2017;18:256–266.
Greene M, Covinsky KE, Valcour V, et al. Geriatric syndromes in older HIV-infected adults. J Acquir Immune Defic Syndr. 2015;69:161.
Langebeek N, Kooij KW, Wit FW, et al. Impact of comorbidity and ageing on health-related quality of life in HIV-positive and HIV-negative individuals. AIDS. 2017;31:1471–1481.
Aung HL, Kootar S, Gates TM, et al. How all-type dementia risk factors and modifiable risk interventions may be relevant to the first-generation aging with HIV infection? Eur Geriatr Med. 2019;10:227–238.
Goodkin K, Miller EN, Cox C, et al. Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study. Lancet HIV. 2017;4:e411-e422.
Cysique LA, Brew BJ. Vascular cognitive impairment and HIV-associated neurocognitive disorder: a new paradigm. J Neurovirol. 2019;25:710–721.
Gelman BB. Neuropathology of HAND with suppressive antiretroviral therapy: encephalitis and neurodegeneration reconsidered. Curr HIV/AIDS Rep. 2015;12:272–279.
Gutierrez J, Byrd D, Yin MT, et al. Relationship between brain arterial pathology and neurocognitive performance among individuals with human immunodeficiency virus. Clin Infect Dis. 2019;68:490–497.
Skrobot OA, Black SE, Chen C, et al. Progress toward standardized diagnosis of vascular cognitive impairment: guidelines from the vascular impairment of cognition classification consensus study. Alzheimers Dement. 2018;14:280–292.
Skrobot OA, O'Brien J, Black S, et al. The vascular impairment of cognition classification consensus study. Alzheimers Dement. 2017;13:624–633.
van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive impairment. Nat Rev Dis Primers. 2018;4:18003.
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:263–269.
Barnes RP, Lacson JCA, Bahrami H. HIV infection and risk of cardiovascular diseases beyond coronary artery disease. Curr Atheroscler Rep. 2017;19:20.
Boccara F Cardiovascular health in an aging HIV population. AIDS. 2017;31:S157.
Demir OM, Candilio L, Fuster D, et al. Cardiovascular disease burden among human immunodeficiency virus-infected individuals. Int J Cardiol. 2018;265:195–203.
Ciccarelli N, Grima P, Fabbiani M, et al. Baseline CD4 (+) T-cell count and cardiovascular risk factors predict the evolution of cognitive performance during 2-year follow-up in HIV-infected patients. Antivir Ther. 2015;20:433–440.
Crystal HA, Weedon J, Holman S, et al. Associations of cardiovascular variables and HAART with cognition in middle-aged HIV-infected and uninfected women. J NeuroVirolog. 2011;17:469.
Fabbiani M, Ciccarelli N, Tana M, et al. Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients. HIV Med. 2013;14:136–144.
Fazeli PL, Crowe M, Ross LA, et al. Cognitive functioning in adults aging with HIV: a cross-sectional analysis of cognitive subtypes and influential factors. J Clin Res HIV AIDS Prev. 2014;1:155–169.
Kalayjian RC, Wu K, Evans S, et al. Proteinuria is associated with neurocognitive impairment in antiretroviral therapy treated HIV-infected individuals. J Acquir Immune Defic Syndr. 2014;67:30–35.
Schouten J, Su T, Wit F, et al. Determinants of reduced cognitive performance in HIV-1-infected middle-aged men on combination antiretroviral therapy. AIDS. 2016;30:1027–1038.
Valcour V, Maki P, Bacchetti P, et al. Insulin resistance and cognition among HIV-infected and HIV-uninfected adult women: the women's interagency HIV study. AIDS Res Hum Retroviruses. 2012;28:447–453.
Valcour VG, Sacktor NC, Paul RH, et al. Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii Aging with HIV cohort. J Acquir Immune Defic Syndr. 2006;43:405–410.
Wright EJ, Grund B, Robertson K, et al. Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons. Neurology. 2010;75:864–873.
Becker JT, Kingsley L, Mullen J, et al. Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men. Neurology. 2009;73:1292–1299.
Huck D, Hanna D, Rubin L, et al. Carotid artery stiffness and cognitive decline among women with or at risk for HIV infection. J Acquir Immune Defic Syndr. 2018;78:338–347.
Azarpazhooh MR, Hachinski V. Vascular cognitive impairment: a preventable component of dementia. Handb Clin Neurol. 2019;167:377–391.
Lake JE, Popov M, Post WS, et al. Visceral fat is associated with brain structure independent of human immunodeficiency virus infection status. J NeuroVirology. 2017;23:385–393.
Rubin LH, Gustafson D, Hawkins KL, et al. Midlife adiposity predicts cognitive decline in the prospective Multicenter AIDS Cohort Study. Neurology. 2019;93:e261–e271.
Cysique LA, Messinis L, Albert SM. Could excess body weight be good for cognitive health in chronic HIV infection? Neurology. 2019;93:95–96.
Haddow LJ, Sudre CH, Sokolska M, et al. Magnetic resonance imaging of cerebral small vessel disease in men living with HIV and HIV-negative men aged 50 and above. AIDS Res Hum Retroviruses. 2019;35:453–460.
Moulignier A, Savatovsky J, Assoumou L, et al. 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. 2018;66:1762–1769.
Watson C, Busovaca E, Foley JM, et al. White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV. J NeuroVirology. 2017;23:422–429.
Mukherjee P, Berman JI, Chung SW, et al. Diffusion tensor MR imaging and fiber tractography: theoretic underpinnings. AJNR Am J Neuroradiol. 2008;29:632–641.
Raja R, Rosenberg G, Caprihan A. Review of diffusion MRI studies in chronic white matter diseases. Neurosci Lett. 2019;694:198–207.
Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12:822–838.
Cysique LA, Heaton RK, Kamminga J, et al. HIV-associated neurocognitive disorder in Australia: a case of a high-functioning and optimally treated cohort and implications for international neuroHIV research. J Neurovirol. 2014;20:258–268.
Cysique LA, Soares JR, Geng G, et al. White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration. J Neurovirol. 2017;23:539–547.
The Kirby Institute. HIV, Viral Hepatitis and Sexually Transmissible Infections in Australia Annual Surveillance Report 2018. UNSW Australia, Sydney NSW 2052; 2018.
Bucci M, Mandelli ML, Berman JI, et al. Quantifying diffusion MRI tractography of the corticospinal tract in brain tumors with deterministic and probabilistic methods. NeuroImage: Clin. 2013;3:361–368.
Smith SM, Jenkinson M, Woolrich MW, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23(suppl 1):S208–S219.
Masters MC, Ances BM. Role of neuroimaging in HIV-associated neurocognitive disorders. Semin Neurol. 2014;34:89–102.
Cysique LA, Moffat K, Moore DM, et al. HIV, vascular and aging injuries in the brain of clinically stable HIV-infected adults: a (1)H MRS study. PLoS One. 2013;8:e61738.
D'Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117:743–753.
Friis-Moller N, Thiebaut R, Reiss P, et al. 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. 2010;17:491–501.
Law MG, Friis-Møller N, El-Sadr WM, et al. The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study. HIV Med. 2006;7:218–230.
Bansal D, Nayakallu RSR, Gudala K, et al. Agreement between Framingham risk score and United Kingdom Prospective Diabetes Study Risk Engine in identifying high coronary heart disease risk in North Indian population. Diabetes Metab J. 2015;39:321–327.
Su T, Mutsaerts HJ, Caan MW, et al. Cerebral blood flow and cognitive function in HIV-infected men with sustained suppressed viremia on combination antiretroviral therapy. AIDS. 2017;31:847–856.
Petito CK, Chen H, Mastri AR, et al. HIV infection of choroid plexus in AIDS and asymptomatic HIV-infected patients suggests that the choroid plexus may be a reservoir of productive infection. J Neurovirol. 1999;5:670–677.
Fletcher E, Raman M, Huebner P, et al. Loss of fornix white matter volume as a predictor of cognitive impairment in cognitively normal elderly individuals. JAMA Neurol. 2013;70:1389–1395.
Metzler-Baddeley C, Mole JP, Sims R, et al. Fornix white matter glia damage causes hippocampal gray matter damage during age-dependent limbic decline. Sci Rep. 2019;9:1060.
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015;14:388–405.
Nichols MJ, Gates TM, Soares JR, et al. Atrophic brain signatures of mild forms of neurocognitive impairment in virally suppressed HIV infection. AIDS. 2018;33:55–66.
Gunbey HP, Ercan K, Findikoglu AS, et al. The limbic degradation of aging brain: a quantitative analysis with diffusion tensor imaging. ScientificWorldJournal. 2014;2014:196513.
Mukherjee P, Chung SW, Berman JI, et al. Diffusion tensor MR imaging and fiber tractography: technical considerations. AJNR Am J Neuroradiol. 2008;29:843–852.
Wassenaar TM, Yaffe K, van der Werf YD, et al. Associations between modifiable risk factors and white matter of the aging brain: insights from diffusion tensor imaging studies. Neurobiol Aging. 2019;80:56–70.
Maillard P, Seshadri S, Beiser A, et al. Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol. 2012;11:1039–1047.
Wang R, Fratiglioni L, Laukka EJ, et al. Effects of vascular risk factors and APOE ε4 on white matter integrity and cognitive decline. Neurology. 2015;84:1128–1135.
Williams OA, An Y, Beason-Held L, et al. Vascular burden and APOE ε4 are associated with white matter microstructural decline in cognitively normal older adults. NeuroImage. 2019;188:572–583.