Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
Authors: 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 ,   COmorBidity in Relation to AIDS (COBRA) Collaboration and the Pharmacokinetic and clinical Observations in PePle over fiftY (POPPY) Study Group, 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 
Published: May 2019

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 &lt; .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 &lt; .05), as well as smaller brain volumes (P &lt; .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.