Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
Author:
Underwood Jonathan12ORCID, De Francesco Davide3ORCID, Cole James H45, Caan Matthan W A6, van Zoest Rosan A7, Schmand Ben A8, Sharp David J4, Sabin Caroline A3, Reiss Peter79, Winston Alan1, Reiss P, Wit F W N M, Schouten J, Kooij K W, van Zoest R A, Elsenga B C, Janssen F R, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra N A, Harskamp-Holwerda A M, Maurer I, Mangas Ruiz M M, Girigorie A F, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand B A, Geurtsen G J, ter Stege J A, Klein Twennaar M, Majoie C B L M, Caan M W A, Su T, Weijer K, Bisschop P H L T, Kalsbeek A, Wezel M, Visser I, Ruhé H G, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall’Olio F, Chiricolo M, Salvioli S, Hoeijmakers J, Pothof J, Prins M, Martens M, Moll S, Berkel J, Totté M, Kovalev S, Gisslén M, Fuchs D, Zetterberg H, Winston A, Underwood J, McDonald L, Stott M, Legg K, Lovell A, Erlwein O, Doyle N, Kingsley C, Sharp D J, Leech R, Cole J H, Zaheri S, Hillebregt M M J, Ruijs Y M C, Benschop D P, Burger D, de Graaff-Teulen M, Guaraldi G, Bürkle A, Sindlinger T, Moreno-Villanueva M, Keller A, Sabin C, de Francesco D, Libert C, Dewaele S, Boffito Marta, Mallon Paddy, Post Frank, Sabin Caroline, Sachikonye Memory, Winston Alan, Anderson Jane, Asboe David, Boffito Marta, Garvey Lucy, Mallon Paddy, Post Frank, Pozniak Anton, Sabin Caroline, Sachikonye Memory, Vera Jaime, Williams Ian, Winston Alan, Post Frank, Campbell Lucy, Yurdakul Selin, Okumu Sara, Pollard Louise, Williams Ian, Otiko Damilola, Phillips Laura, Laverick Rosanna, Fisher Martin, Clarke Amanda, Vera Jaime, Bexley Andrew, Richardson Celia, Mallon Paddy, Macken Alan, Ghavani-Kia Bijan, Maher Joanne, Byrne Maria, Flaherty Ailbhe, Anderson Jane, Mguni Sifiso, Clark Rebecca, Nevin-Dolan Rhiannon, Pelluri Sambasivarao, Johnson Margaret, Ngwu Nnenna, Hemat Nargis, Jones Martin, Carroll Anne, Whitehouse Andrew, Burgess Laura, Babalis Daphne, Winston Alan, Garvey Lucy, Underwood Jonathan, Stott Matthew, McDonald Linda, Boffito Marta, Asboe David, Pozniak Anton, Higgs Chris, Seah Elisha, Fletcher Stephen, Anthonipillai Michelle, Moyes Ashley, Deats Katie, Syed Irtiza, Matthews Clive,
Affiliation:
1. Division of Infectious Diseases, Imperial College London, UK 2. Department of Infectious Diseases, Cardiff and Vale University Health Board, Cardiff, UK 3. Department of Infection and Population Health, University College London, UK 4. Division of Brain Sciences, Imperial College London, UK 5. Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, UK 6. Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands 7. Departments of Global Health and Internal Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Infection and Immunity Institute, and Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, The Netherlands 8. Department of Medical Psychology, Academic Medical Center, Amsterdam, The Netherlands 9. HIV Monitoring Foundation, Amsterdam, the Netherlands
Abstract
Abstract
Background
The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.
Methods
Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.
Results
The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).
There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.
Conclusion
Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
Funder
European Union Seventh Framework Programme National Institute for Health Research (NIHR) Professorship NIHR Imperial Biomedical Research Centre Netherlands Organisation for Health Research and Development ViiV Healthcare Gilead Sciences Janssen Pharmaceutica N.V. Bristol-Myers Squibb National Institutes of Health
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Oncology
Cited by
16 articles.
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