Jonathan Underwood1, James H Cole2, Matthan Caan3, Davide De Francesco4, Robert Leech2, Rosan A van Zoest5, Tanja Su3, Gert J Geurtsen6, Ben A Schmand6, Peter Portegies7, Maria Prins8, Ferdinand W N M Wit5,9,10, Caroline A Sabin4, Charles Majoie3, Peter Reiss5,9,10, Alan Winston1, David J Sharp2. 1. Divisions of Infectious Diseases. 2. Brain Sciences, Imperial College London, United Kingdom. 3. Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands. 4. Department of Infection and Population Health, University College London, United Kingdom. 5. Department of Global Health, Academic Medical Center, and Amsterdam Institute for Global Health and Development. 6. Department of Medical Psychology. 7. Department of Neurology, Academic Medical Center. 8. Public Health Service Amsterdam. 9. HIV Monitoring Foundation. 10. Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Abstract
BACKGROUND: Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people living with human immunodeficiency virus (HIV). We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multimodal neuroimaging from the Comorbidity in Relation to AIDS (COBRA) cohort. METHODS: Cognitive function, brain tissue volumes, and white matter microstructure were assessed in 134 HIV-infected patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion, and volumetric data, taking advantage of the complementary information they provide. RESULTS: Compared to the highly comparable control group, cognitive function was impaired in 4 of the 6 cognitive domains tested (median global T-scores: 50.8 vs 54.2; P < .001). Patients had lower gray but not white matter volumes, observed principally in regions where structure generally did not correlate with cognitive function. Widespread abnormalities in white matter microstructure were also seen, including reduced fractional anisotropy with increased mean and radial diffusivity. In contrast to the gray matter, these diffusion abnormalities correlated with cognitive function. Multivariate neuroimaging analysis identified a neuroimaging phenotype associated with poorer cognitive function, HIV infection, and systemic immune activation. CONCLUSIONS: Cognitive impairment, lower gray matter volume, and white matter microstructural abnormalities were evident in HIV-infected individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-infected individuals.
BACKGROUND: Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people living with human immunodeficiency virus (HIV). We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multimodal neuroimaging from the Comorbidity in Relation to AIDS (COBRA) cohort. METHODS: Cognitive function, brain tissue volumes, and white matter microstructure were assessed in 134 HIV-infected patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion, and volumetric data, taking advantage of the complementary information they provide. RESULTS: Compared to the highly comparable control group, cognitive function was impaired in 4 of the 6 cognitive domains tested (median global T-scores: 50.8 vs 54.2; P < .001). Patients had lower gray but not white matter volumes, observed principally in regions where structure generally did not correlate with cognitive function. Widespread abnormalities in white matter microstructure were also seen, including reduced fractional anisotropy with increased mean and radial diffusivity. In contrast to the gray matter, these diffusion abnormalities correlated with cognitive function. Multivariate neuroimaging analysis identified a neuroimaging phenotype associated with poorer cognitive function, HIV infection, and systemic immune activation. CONCLUSIONS: Cognitive impairment, lower gray matter volume, and white matter microstructural abnormalities were evident in HIV-infected individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-infected individuals.
Authors: Tanja Su; Judith Schouten; Gert J Geurtsen; Ferdinand W Wit; Ineke G Stolte; Maria Prins; Peter Portegies; Matthan W A Caan; Peter Reiss; Charles B Majoie; Ben A Schmand Journal: AIDS Date: 2015-03-13 Impact factor: 4.177
Authors: Ming-Chang Chiang; Rebecca A Dutton; Kiralee M Hayashi; Oscar L Lopez; Howard J Aizenstein; Arthur W Toga; James T Becker; Paul M Thompson Journal: Neuroimage Date: 2006-10-10 Impact factor: 6.556
Authors: Kevin R Robertson; Marlene Smurzynski; Thomas D Parsons; Kunling Wu; Ronald J Bosch; Julia Wu; Justin C McArthur; Ann C Collier; Scott R Evans; Ron J Ellis Journal: AIDS Date: 2007-09-12 Impact factor: 4.177
Authors: Glenn T Stebbins; Clifford A Smith; Russell E Bartt; Harold A Kessler; Oluwatoyin M Adeyemi; Eileen Martin; Jennifer L Cox; Roland Bammer; Michael E Moseley Journal: J Acquir Immune Defic Syndr Date: 2007-12-15 Impact factor: 3.731
Authors: Talia M Nir; Neda Jahanshad; Edgar Busovaca; Lauren Wendelken; Krista Nicolas; Paul M Thompson; Victor G Valcour Journal: Hum Brain Mapp Date: 2013-01-30 Impact factor: 5.038
Authors: Sergio Serrano-Villar; Talia Sainz; Sulggi A Lee; Peter W Hunt; Elizabeth Sinclair; Barbara L Shacklett; April L Ferre; Timothy L Hayes; Ma Somsouk; Priscilla Y Hsue; Mark L Van Natta; Curtis L Meinert; Michael M Lederman; Hiroyu Hatano; Vivek Jain; Yong Huang; Frederick M Hecht; Jeffrey N Martin; Joseph M McCune; Santiago Moreno; Steven G Deeks Journal: PLoS Pathog Date: 2014-05-15 Impact factor: 6.823
Authors: Margaret T May; Mark Gompels; Valerie Delpech; Kholoud Porter; Chloe Orkin; Stephen Kegg; Phillip Hay; Margaret Johnson; Adrian Palfreeman; Richard Gilson; David Chadwick; Fabiola Martin; Teresa Hill; John Walsh; Frank Post; Martin Fisher; Jonathan Ainsworth; Sophie Jose; Clifford Leen; Mark Nelson; Jane Anderson; Caroline Sabin Journal: AIDS Date: 2014-05-15 Impact factor: 4.177
Authors: Isaac H Solomon; Sukrutha Chettimada; Vikas Misra; David R Lorenz; Robert J Gorelick; Benjamin B Gelman; Susan Morgello; Dana Gabuzda Journal: Mol Neurobiol Date: 2019-11-05 Impact factor: 5.590
Authors: David R Goulding; Andrew Kraft; Peter R Mouton; Christopher A McPherson; Valeria Avdoshina; Italo Mocchetti; G Jean Harry Journal: Neurotox Res Date: 2019-07-08 Impact factor: 3.911
Authors: Emily W Paolillo; Sarah M Inkelis; Anne Heaton; Rowan Saloner; Raeanne C Moore; David J Moore Journal: Alcohol Alcohol Date: 2019-03-01 Impact factor: 2.826
Authors: Laura E Petersen; Talita S A Baptista; Júlia K Molina; Julia G Motta; Aline do Prado; Deise M Piovesan; Tatiana de Nardi; Thiago W Viola; Érica L M Vieira; Antonio L Teixeira; Rodrigo Grassi-Oliveira; Moisés Evandro Bauer Journal: Clin Rheumatol Date: 2018-01-25 Impact factor: 2.980