Joint trajectories of brain atrophy, white matter hyperintensities and cognition quantify brain maintenance

Abstract

Brain maintenance – the preservation of brain structure or function relevant to cognitive performance – remains challenging to quantify. Here, we propose a domain-general brain maintenance index derived by jointly modelling the longitudinal co-evolution of ageing-related atrophy (via medial temporal lobe to ventricle ratio, MTLV-ratio), white matter hyperintensities (WMH), and global cognition assessed by the preclinical Alzheimer’s cognitive composite (PACC5) using latent growth curve modelling. We demonstrate its utility in 543 cognitively unimpaired older adults from the DELCODE cohort, followed annually over four years. We show that changes in MTLV-ratio and WMH additively predict cognitive change. We further show that higher neuroticism, depressive symptoms, lower openness, and faster biological ageing are related to unfavourable domain-specific trajectories and poorer brain maintenance. Our findings highlight the combined relevance of WMH and ageing-related atrophy dynamics for brain maintenance. Maintaining cerebrovascular and mental health alongside cognitive engagement could promote brain maintenance, delay cognitive decline and dementia.

Metadata

Item Type:	Article
Authors/Creators:	Menze, I. https://orcid.org/0009-0001-4567-1655 Bernal, J. https://orcid.org/0000-0003-3167-5134 Kievit, R.A. Tripathi, K.P. https://orcid.org/0000-0002-3998-599X Kaleck, T. Yakupov, R. https://orcid.org/0000-0002-3868-284X Altenstein, S. Bartels, C. Buerger, K. Butryn, M. Dechent, P. Ewers, M. https://orcid.org/0000-0001-5231-1714 Fliessbach, K. Frommann, I. https://orcid.org/0000-0002-7244-2014 Gemenetzi, M. Glanz, W. Gref, D. https://orcid.org/0000-0003-2497-9324 Hellmann-Regen, J. https://orcid.org/0000-0003-0411-9204 Hetzer, S. Incesoy, E.I. Janowitz, D. Kiliman, I. Kleineidam, L. https://orcid.org/0009-0006-3309-6856 Kronmüller, M.T. Laske, C. van Lent, D.M. https://orcid.org/0000-0002-7392-9289 Lüsebrink, F. Perneczky, R. https://orcid.org/0000-0003-1981-7435 Peters, O. https://orcid.org/0000-0003-0568-2998 Preis, L. Priller, J. https://orcid.org/0000-0001-7596-0979 Rauchmann, B.-S. https://orcid.org/0000-0003-4547-6240 Rostamzadeh, A. Roeske, S. Scheffler, K. Schott, B.-H. https://orcid.org/0000-0002-8237-4481 Schneider, A. https://orcid.org/0000-0001-9540-8700 Sodenkamp, S. Spottke, A. Spruth, E.J. Stark, M. https://orcid.org/0009-0005-3812-023X Teipel, S. Wagner, M. https://orcid.org/0000-0003-2589-6440 Wiltfang, J. https://orcid.org/0000-0003-1492-5330 Jessen, F. Ramirez, A. https://orcid.org/0000-0003-4991-763X Schreiber, S. https://orcid.org/0000-0003-4439-4374 Düzel, E. Ziegler, G. https://orcid.org/0000-0001-6589-6416
Copyright, Publisher and Additional Information:	© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.
Keywords:	Humans; White Matter; Atrophy; Cognition; Brain; Aging; Magnetic Resonance Imaging; Female; Male; Aged; Aged, 80 and over; Cognitive Dysfunction
Dates:	Submitted: 24 June 2025 Accepted: 17 June 2026 Published (online): 4 July 2026 Published: 4 July 2026
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health
Date Deposited:	23 Sep 2026 15:06
Last Modified:	23 Sep 2026 15:06
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s41467-026-74957-2
Related URLs:	PubMed URL
Sustainable Development Goals:
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:245843

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Joint trajectories of brain atrophy, white matter hyperintensities and cognition quantify brain maintenance

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