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Validation of a novel multivariate method of defining HIV-associated cognitive impairment

Underwood, Jonathan, De Francesco, Davide, Cole, James H., Caan, Matthan W. A., van Zoest, Rosan A., Schmand, Ben A., Sharp, David J., Sabin, Caroline A., Reiss, Peter, Winston, Alan, 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 and Matthews, Clive 2019. Validation of a novel multivariate method of defining HIV-associated cognitive impairment. Open Forum Infectious Diseases 6 (6) , ofz198. 10.1093/ofid/ofz198

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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 selfreported health status. This may be due to the statistical advantage of using a multivariate approach

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Oxford University Press
ISSN: 2328-8957
Date of First Compliant Deposit: 8 August 2019
Date of Acceptance: 29 April 2019
Last Modified: 09 Aug 2019 10:27

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