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

Authors

Inga Menze, Jose Bernal, Rogier A Kievit, Kumar Parijat Tripathi, Timo Kaleck, Renat Yakupov, Slawek Altenstein, Claudia Bartels, Katharina Buerger, Michaela Butryn, Peter Dechent, Michael Ewers, Klaus Fliessbach, Ingo Frommann, Maria Gemenetzi, Wenzel Glanz, Daria Gref, Julian Hellmann-Regen, Stefan Hetzer, Enise I Incesoy, Daniel Janowitz, Ingo Kiliman, Luca Kleineidam, Marie Theres Kronmüller, Christoph Laske, Debora Melo van Lent, Falk Lüsebrink, Robert Perneczky, Oliver Peters, Lukas Preis, Josef Priller, Boris-Stephan Rauchmann, Ayda Rostamzadeh, Sandra Roeske, Klaus Scheffler, Björn-Hendrik Schott, Anja Schneider, Sebastian Sodenkamp, Annika Spottke, Eike Jakob Spruth, Melina Stark, Stefan Teipel, Michael Wagner, Jens Wiltfang, Frank Jessen, Alfredo Ramirez, Stefanie Schreiber, Emrah Düzel, Gabriel Ziegler

Published in

Nature communications. Volume 17. Issue 1. Jul 04, 2026. Epub Jul 04, 2026.

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.

PMID:
42401584
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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