“The association of diabetes with Alzheimer’s disease biomarkers and vascular burden across European aging and memory clinic cohorts”
Authors: Veerle van Gils, Willemijn J. Jansen, Wiesje M. van der Flier, Pablo Martinez-Lage, Jakub Hort, Inez H. G. B. Ramakers, Olivier Rouaud, Markku Laakso, Sebastiaan Engelborghs, Julius Popp, Alberto Lleó, Anders Wallin, Magda Tsolaki, Charlotte E. Teunissen, Rik Vandenberghe, Yvonne Freund-Levi, Lutz Frölich, Henrik Zetterberg, Johannes Streffer, Simon Lovestone, Justine Moonen, Argonde van Harten, Katerina Veverová, Nienke Legdeur, Anouk den Braber, Daniel Damian, Anette Hall, Janita Bralten, Giuseppe Fanelli, Barbara Franke, Geert Poelmans, Monica Bulló, Susana Jimenez-Murcia, Fernando Fernandez-Aranda, Jordi Salas-Salvadó, Søren Dalsgaard, Pieter Jelle Visser, Stephanie J. B. Vos
Abstract:
Introduction: It remains unclear whether diabetes mellitus (DM) is associated with Alzheimer’s disease (AD) pathology and associated vascular burden.
Methods: We included cognitively normal (CN), mild cognitive impairment (MCI), and dementia individuals. We assessed associations between DM and AD biomarkers (amyloid beta [Aβ], phosphorylated tau‐181 [p‐tau181], total tau [t‐tau], and medial temporal atrophy [MTA]) and vascular burden (white matter hyperintensities, microbleeds) by logistic regression. Secondary analyses assessed associations between DM and profiles of Aβ combined with p‐tau181/t‐tau/MTA/white matter hyperintensity/microbleeds.
Results: We included 5550 participants (65.8+‐8.7 years, 8.7% DM). DM was associated with lower odds of abnormal AD biomarkers: Aβ in MCI (odds ratio [OR] = 0.70, 95% confidence interval [CI]: 0.51–0.95, p = 0.02) and dementia (OR = 0.44, 0.26–0.78, p = 0.003), and p‐tau181 in dementia (OR = 0.64, 0.41–1.00, p = 0.045). Secondary analyses indicated associations of DM with abnormal t‐tau (OR = 1.57, 1.00–2.46, p = 0.048) and MTA (OR = 1.96, 1.05–3.68, p = 0.04) only in CN individuals with normal Aβ.
Discussion: In cognitively impaired individuals, DM was associated with lower odds of Aβ pathology, whereas DM was associated with neurodegeneration markers in CN individuals without Aβ pathology.
DOI: https://doi.org/10.1002/alz.70804
Published online: 30 October 2025 in the journal of Alzheimer’s & Dementia