White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants

Brugulat Serrat, Anna, 1986-; Salvadó, Glòria; Operto, Grégory; Cacciaglia, Raffaele; Sudre, Carole H.; Grau-Rivera, Oriol; Suárez-Calvet, Marc; Falcón, Carles; Sánchez Benavides, Gonzalo; Gramunt Fombuena, Nina; Minguillón, Carolina; Fauria, Karine; Barkhof, Frederik; Molinuevo, José Luis; Gispert López, Juan Domingo; ALFA Study

White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants

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dc.contributor.author Brugulat Serrat, Anna, 1986-
dc.contributor.author Salvadó, Glòria
dc.contributor.author Operto, Grégory
dc.contributor.author Cacciaglia, Raffaele
dc.contributor.author Sudre, Carole H.
dc.contributor.author Grau-Rivera, Oriol
dc.contributor.author Suárez-Calvet, Marc
dc.contributor.author Falcón, Carles
dc.contributor.author Sánchez Benavides, Gonzalo
dc.contributor.author Gramunt Fombuena, Nina
dc.contributor.author Minguillón, Carolina
dc.contributor.author Fauria, Karine
dc.contributor.author Barkhof, Frederik
dc.contributor.author Molinuevo, José Luis
dc.contributor.author Gispert López, Juan Domingo
dc.contributor.author ALFA Study
dc.date.accessioned 2020-06-05T06:28:31Z
dc.date.available 2020-06-05T06:28:31Z
dc.date.issued 2020
dc.description.abstract White matter hyperintensities (WMH) have been extensively associated with cognitive impairment and reductions in gray matter volume (GMv) independently. This study explored whether WMH lesion volume mediates the relationship between cerebral patterns of GMv and cognition in 521 (mean age 57.7 years) cognitively unimpaired middle-aged individuals. Episodic memory (EM) was measured with the Memory Binding Test and executive functions (EF) using five WAIS-IV subtests. WMH were automatically determined from T2 and FLAIR sequences and characterized using diffusion-weighted imaging (DWI) parameters. WMH volume was entered as a mediator in a voxel-wise mediation analysis relating GMv and cognitive performance (with both EM and EF composites and the individual tests independently). The mediation model was corrected by age, sex, education, number of Apolipoprotein E (APOE)-ε4 alleles and total intracranial volume. We found that even at very low levels of WMH burden in the cohort (median volume of 3.2 mL), higher WMH lesion volume was significantly associated with a widespread pattern of lower GMv in temporal, frontal, and cerebellar areas. WMH mediated the relationship between GMv and EF, mainly driven by processing speed, but not EM. DWI parameters in these lesions were compatible with incipient demyelination and axonal loss. These findings lead to the reflection on the relevance of the control of cardiovascular risk factors in middle-aged individuals as a valuable preventive strategy to reduce or delay cognitive decline.
dc.description.sponsorship Research conducted by José Luis Molinuevo receives support from: the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AMYPAD grant agreement #115952; the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EPAD grant agreement #115736 and the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AETIONOMY grant #115568. He is/has been a scientific consultant and/or attended scientific advisory boards of Alergan, Roche diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, Raman Health. Research conducted by Frederik Barkhof receives support from AMYPAD (IMI); EuroPOND (H2020); UK MS Society; Dutch MS Society; PICTURE (IMDI-NWO); NIHR UCLH; Biomedical Research Centre (BRC) and ECTRIMS-MAGNIMS. He has received consultancy fees from Bayer Pharma, Biogen-IDEC, TEVA, Merck, Novartis, Roche, Jansen Research, Genzyme-Sanofi, IXICO Ltd, GeNeuro and Apitope Ltd.
dc.format.mimetype application/pdf
dc.identifier.citation Brugulat-Serrat A, Salvadó G, Operto G, Cacciaglia R, Sudre CH, Grau-Rivera O, White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants. Hum Brain Mapp. 2020 Apr 1; 41(5):1309-22. DOI: 10.1002/hbm.24877
dc.identifier.doi http://dx.doi.org/10.1002/hbm.24877
dc.identifier.issn 1065-9471
dc.identifier.uri http://hdl.handle.net/10230/44912
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartof Human Brain Mapping. 2020 Apr 1;41(5):1309-22
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115736
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115568
dc.rights This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
dc.subject.keyword Aging
dc.subject.keyword Cognition
dc.subject.keyword Hypertension
dc.subject.keyword Prevention
dc.subject.keyword Vascular risk factors
dc.subject.keyword White matter lesions
dc.title White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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