No evidence for accelerated ageing-related brain pathology in treated HIV: longitudinal neuroimaging results from the Comorbidity in Relation to AIDS (COBRA) project
File(s)
Accepted version
Supporting information
Author(s)
Type
Journal Article
Abstract
Background
Despite successful antiretroviral therapy people living with HIV (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function and cognitive impairment. This has raised concerns that PLWH may experience accelerated ageing-related brain pathology.
Methods
We performed a multi-centre longitudinal study of 134 virologically-suppressed PLWH (median age = 56.0 years) and 79 demographically-similar HIV-negative controls (median age = 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multi-modality neuroimaging (T1-weighted, T2-weighted, diffusion-MRI, resting-state functional-MRI, spectroscopy, arterial spin labelling) at baseline and after two-year follow-up. Group differences in rates of change were assessed using linear mixed effects models.
Results
123 PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval = 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking, alcohol use, recreational drug use, blood pressure, body-mass index or cholesterol levels.
At baseline, PLWH had poorer global cognitive performance (P<0.01), lower grey matter volume (P=0.04), higher white matter hyperintensity load (P=0.02), abnormal white-matter microstructure (P<0.005) and greater ‘brain-predicted age difference’ (P=0.01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P>0.1). Cognitive performance was stable across the study period in both groups.
Conclusions
Our finding indicate that when receiving successful treatment, middle-aged PLWH are not at increased risk of accelerated ageing-related brain changes or cognitive decline over two years, when compared to closely-matched HIV-negative controls.
Despite successful antiretroviral therapy people living with HIV (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function and cognitive impairment. This has raised concerns that PLWH may experience accelerated ageing-related brain pathology.
Methods
We performed a multi-centre longitudinal study of 134 virologically-suppressed PLWH (median age = 56.0 years) and 79 demographically-similar HIV-negative controls (median age = 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multi-modality neuroimaging (T1-weighted, T2-weighted, diffusion-MRI, resting-state functional-MRI, spectroscopy, arterial spin labelling) at baseline and after two-year follow-up. Group differences in rates of change were assessed using linear mixed effects models.
Results
123 PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval = 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking, alcohol use, recreational drug use, blood pressure, body-mass index or cholesterol levels.
At baseline, PLWH had poorer global cognitive performance (P<0.01), lower grey matter volume (P=0.04), higher white matter hyperintensity load (P=0.02), abnormal white-matter microstructure (P<0.005) and greater ‘brain-predicted age difference’ (P=0.01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P>0.1). Cognitive performance was stable across the study period in both groups.
Conclusions
Our finding indicate that when receiving successful treatment, middle-aged PLWH are not at increased risk of accelerated ageing-related brain changes or cognitive decline over two years, when compared to closely-matched HIV-negative controls.
Date Issued
2018-06-01
Date Acceptance
2017-12-13
Citation
Clinical Infectious Diseases, 2018, 66 (12), pp.1899-1909
ISSN
1058-4838
Publisher
Oxford University Press (OUP)
Start Page
1899
End Page
1909
Journal / Book Title
Clinical Infectious Diseases
Volume
66
Issue
12
Copyright Statement
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Clinical Infectious Diseases following peer review. The version of record James H Cole, Matthan WA Caan, Jonathan Underwood, Davide De Francesco, Rosan A van Zoest, Ferdinand WNM Wit, Henk JMM Mutsaerts, Rob Leech, Gert J Geurtsen, Peter Portegies, Charles BLM Majoie, Maarten F Schim van der Loeff, Caroline A Sabin, Peter Reiss, Alan Winston, David J Sharp, ; No evidence for accelerated ageing-related brain pathology in treated HIV: longitudinal neuroimaging results from the Comorbidity in Relation to AIDS (COBRA) project, Clinical Infectious Diseases, is available online at: https://dx.doi.org/10.1093/cid/cix1124
Sponsor
Commission of the European Communities
National Institute for Health Research
Grant Number
305522
NIHR-RP-011-048
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
HIV
aging
neuroimaging
brain structure
cognitive function
COMBINATION ANTIRETROVIRAL THERAPY
CEREBRAL-BLOOD-FLOW
HIV-INFECTION
RISK-FACTORS
MEN
DISEASE
ATROPHY
INJURY
AGE
NEURODEGENERATION
COBRA collaboration
06 Biological Sciences
11 Medical And Health Sciences
Publication Status
Published
Date Publish Online
2018-01-04