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

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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), patientreported 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.
Keywords
OLDER-PEOPLE, REGISTRATION, PREVALENCE, VALIDITY, SCORES, MEN, cognitive impairment, HIV, multivariate, neuroimaging

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MLA
Underwood, Jonathan, et al. “Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment.” OPEN FORUM INFECTIOUS DISEASES, vol. 6, no. 6, 2019.
APA
Underwood, J., de Francesco, D., Cole, J. H., Caan, M. W., van Zoest, R. A., Schmand, B. A., … Matthews, C. (2019). Validation of a novel multivariate method of defining HIV-associated cognitive impairment. OPEN FORUM INFECTIOUS DISEASES, 6(6).
Chicago author-date
Underwood, Jonathan, Davide de Francesco, James H Cole, Matthan WA Caan, Rosan A van Zoest, Ben A Schmand, David J Sharp, et al. 2019. “Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment.” OPEN FORUM INFECTIOUS DISEASES 6 (6).
Chicago author-date (all authors)
Underwood, Jonathan, Davide de Francesco, James H Cole, Matthan WA Caan, Rosan A van Zoest, Ben A Schmand, David J Sharp, Caroline A Sabin, Peter Reiss, Alan Winston, P Reiss, FWNM Wit, J Schouten, KW Kooij, RA van Zoest, BC Elsenga, FR Janssen, M Heidenrijk, W Zikkenheiner, M van der Valk, NA Kootstra, AM Harskamp-Holwerda, I Maurer, MM Mangas Ruiz, AF Girigorie, J Villaudy, E Frankin, A Pasternak, B Berkhout, T van der Kuyl, P Portegies, BA Schmand, GJ Geurtsen, JA ter Stege, M Klein Twennaar, CBLM Majoie, MWA Caan, T Su, K Weijer, PHLT Bisschop, A Kalsbeek, M Wezel, I Visser, HG Ruhe, C Franceschi, P Garagnani, C Pirazzini, M Capri, F Dall’Olio, M Chiricolo, S Salvioli, J Hoeijmakers, J Pothof, M Prins, M Martens, S Moll, J Berkel, M Totte, S Kovalev, M Gisslen, D Fuchs, H Zetterberg, A Winston, J Underwood, L McDonald, M Stott, K Legg, A Lovell, O Erlwein, N Doyle, C Kingsley, DJ Sharp, R Leech, JH Cole, S Zaheri, MMJ Hillebregt, YMC Ruijs, DP Benschop, D Burger, M de Graaff-Teulen, G Guaraldi, A Buerkle, T Sindlinger, M Moreno-Villanueva, A Keller, C Sabin, D de Francesco, Claude Libert, Sylviane Dewaele, Marta Boffito, Paddy Mallon, Frank Post, Caroline Sabin, Memory Sachikonye, Jane Anderson, David Asboe, Lucy Garvey, Anton Pozniak, Jaime Vera, Ian Williams, Lucy Campbell, Selin Yurdakul, Sara Okumu, Louise Pollard, Damilola Otiko, Laura Phillips, Rosanna Laverick, Martin Fisher, Amanda Clarke, Andrew Bexley, Celia Richardson, Alan Macken, Bijan Ghavani-Kia, Joanne Maher, Maria Byrne, Ailbhe Flaherty, Sifiso Mguni, Rebecca Clark, Rhiannon Nevin-Dolan, Sambasivarao Pelluri, Margaret Johnson, Nnenna Ngwu, Nargis Hemat, Martin Jones, Anne Carroll, Andrew Whitehouse, Laura Burgess, Daphne Babalis, Matthew Stott, Linda McDonald, Chris Higgs, Elisha Seah, Stephen Fletcher, Michelle Anthonipillai, Ashley Moyes, Katie Deats, Irtiza Syed, and Clive Matthews. 2019. “Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment.” OPEN FORUM INFECTIOUS DISEASES 6 (6).
Vancouver
1.
Underwood J, de Francesco D, Cole JH, Caan MW, van Zoest RA, Schmand BA, et al. Validation of a novel multivariate method of defining HIV-associated cognitive impairment. OPEN FORUM INFECTIOUS DISEASES. 2019;6(6).
IEEE
[1]
J. Underwood et al., “Validation of a novel multivariate method of defining HIV-associated cognitive impairment,” OPEN FORUM INFECTIOUS DISEASES, vol. 6, no. 6, 2019.
@article{8625680,
  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), patientreported 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.},
  articleno    = {ofz198},
  author       = {Underwood, Jonathan and de Francesco, Davide and Cole, James H and Caan, Matthan WA and van Zoest, Rosan A and Schmand, Ben A and Sharp, David J and Sabin, Caroline A and Reiss, Peter and Winston, Alan and Reiss, P and Wit, FWNM and Schouten, J and Kooij, KW and van Zoest, RA and Elsenga, BC and Janssen, FR and Heidenrijk, M and Zikkenheiner, W and van der Valk, M and Kootstra, NA and Harskamp-Holwerda, AM and Maurer, I and Mangas Ruiz, MM and Girigorie, AF and Villaudy, J and Frankin, E and Pasternak, A and Berkhout, B and van der Kuyl, T and Portegies, P and Schmand, BA and Geurtsen, GJ and ter Stege, JA and Klein Twennaar, M and Majoie, CBLM and Caan, MWA and Su, T and Weijer, K and Bisschop, PHLT and Kalsbeek, A and Wezel, M and Visser, I and Ruhe, HG and Franceschi, C and Garagnani, P and Pirazzini, C and Capri, M and Dall'Olio, F and Chiricolo, M and Salvioli, S and Hoeijmakers, J and Pothof, J and Prins, M and Martens, M and Moll, S and Berkel, J and Totte, M and Kovalev, S and Gisslen, M and Fuchs, D and Zetterberg, H and Winston, A and Underwood, J and McDonald, L and Stott, M and Legg, K and Lovell, A and Erlwein, O and Doyle, N and Kingsley, C and Sharp, DJ and Leech, R and Cole, JH and Zaheri, S and Hillebregt, MMJ and Ruijs, YMC and Benschop, DP and Burger, D and de Graaff-Teulen, M and Guaraldi, G and Buerkle, A and Sindlinger, T and Moreno-Villanueva, M and Keller, A and Sabin, C and de Francesco, D and Libert, Claude and Dewaele, Sylviane and Boffito, Marta and Mallon, Paddy and Post, Frank and Sabin, Caroline and Sachikonye, Memory and Anderson, Jane and Asboe, David and Garvey, Lucy and Pozniak, Anton and Vera, Jaime and Williams, Ian and Campbell, Lucy and Yurdakul, Selin and Okumu, Sara and Pollard, Louise and Otiko, Damilola and Phillips, Laura and Laverick, Rosanna and Fisher, Martin and Clarke, Amanda and Bexley, Andrew and Richardson, Celia and Macken, Alan and Ghavani-Kia, Bijan and Maher, Joanne and Byrne, Maria and Flaherty, Ailbhe and Mguni, Sifiso and Clark, Rebecca and Nevin-Dolan, Rhiannon and Pelluri, Sambasivarao and Johnson, Margaret and Ngwu, Nnenna and Hemat, Nargis and Jones, Martin and Carroll, Anne and Whitehouse, Andrew and Burgess, Laura and Babalis, Daphne and Stott, Matthew and McDonald, Linda and Higgs, Chris and Seah, Elisha and Fletcher, Stephen and Anthonipillai, Michelle and Moyes, Ashley and Deats, Katie and Syed, Irtiza and Matthews, Clive},
  issn         = {2328-8957},
  journal      = {OPEN FORUM INFECTIOUS DISEASES},
  keywords     = {OLDER-PEOPLE,REGISTRATION,PREVALENCE,VALIDITY,SCORES,MEN,cognitive impairment,HIV,multivariate,neuroimaging},
  language     = {eng},
  number       = {6},
  pages        = {9},
  title        = {Validation of a novel multivariate method of defining HIV-associated cognitive impairment},
  url          = {http://dx.doi.org/10.1093/ofid/ofz198},
  volume       = {6},
  year         = {2019},
}

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