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Linking latent trajectories of ageing-related atrophy, white matter hyperintensities, and cognitive ageing over four years: Insights into brain maintenance

Menze, I.; Bernal, J.; Kievit, R. A.; Yakupov, R.; Altenstein, S.; Bartels, C.; Buerger, K.; Butryn, M.; Dechent, P.; Ewers, M.; Fliessbach, K.; Frommann, I.; Gemenetzi, M.; Glanz, W.; Gref, D.; Hellmann-Regen, J.; Hetzer, S.; Incesoy, E. I.; Janowitz, D.; Kiliman, I.; Kleineidam, L.; Kronmüller, M. T.; Laske, C.; Melo van Lent, D.; Lüsebrink, F.; Perneczky, R.; Peters, O.; Preis, L.; Priller, J.; Ramirez, A.; Rauchmann, B.-S.; Rostamzadeh, A.; Roeske, S.; Scheffler, K.; Schott, B. H.; Schneider, A.; Sodenkamp, S.; Spottke, A.; Spruth, E. J.; Stark, M.; Teipel, S.; Wagner, M.; Wiltfang, J.;

2025-06-16 neurology
10.1101/2025.06.16.25329648 medRxiv
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IntroductionWe studied brain maintenance, examining the co-evolution of ageing-related atrophy, white matter hyperintensities (WMH), and cognition, alongside domain-specific and domain-general contributions of lifestyle and personality. MethodsIn 543 cognitively unimpaired DELCODE participants, we modelled four-year interrelations between medial temporal lobe to ventricle ratio (MTLV-ratio), WMH, and PACC5 performance using latent growth curve modelling. We quantified unique contributions of brain changes to cognitive change and derived a domain-general brain maintenance index. Associations with lifestyle and personality were examined post-hoc. ResultsSteeper MTLV-ratio decline related to baseline WMH and its progression. Brain-domain changes independently contributed to cognitive changes. Neuroticism, depressive symptoms, and low cognitive engagement related to unfavourable domain-specific trajectories and brain maintenance index. DiscussionDynamics of WMH and ageing-related atrophy on cognitive ageing highlight their relevance for brain maintenance. Our results suggest that maintaining cerebrovascular and mental health alongside cognitive engagement could promote brain maintenance, delay cognitive decline and dementia.

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