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The association of diabetes with Alzheimer's disease biomarkers and vascular burden across European aging and memory clinic cohorts

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...

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Main Authors: van Gils, Veerle (Author) , Jansen, Willemijn J. (Author) , van der Flier, Wiesje M. (Author) , Martinez-Lage, Pablo (Author) , Hort, Jakub (Author) , Ramakers, Inez H. G. B. (Author) , Rouaud, Olivier (Author) , Laakso, Markku (Author) , Engelborghs, Sebastiaan (Author) , Popp, Julius (Author) , Lleó, Alberto (Author) , Wallin, Anders (Author) , Tsolaki, Magda (Author) , Teunissen, Charlotte E. (Author) , Vandenberghe, Rik (Author) , Freund-Levi, Yvonne (Author) , Frölich, Lutz (Author) , Zetterberg, Henrik (Author) , Streffer, Johannes (Author) , Lovestone, Simon (Author) , Moonen, Justine (Author) , van Harten, Argonde (Author) , Veverová, Katerina (Author) , Legdeur, Nienke (Author) , den Braber, Anouk (Author) , Damian, Daniel (Author) , Hall, Anette (Author) , Bralten, Janita (Author) , Fanelli, Giuseppe (Author) , Franke, Barbara (Author) , Poelmans, Geert (Author) , Bulló, Monica (Author) , Jimenez-Murcia, Susana (Author) , Fernandez-Aranda, Fernando (Author) , Salas-Salvadó, Jordi (Author) , Dalsgaard, Søren (Author) , Visser, Pieter Jelle (Author) , Vos, Stephanie J. B. (Author)
Format: Article (Journal)
Language:English
Published: October 2025
In: Alzheimer's and dementia
Year: 2025, Volume: 21, Issue: 10, Pages: 1-12
ISSN:1552-5279
DOI:10.1002/alz.70804
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/alz.70804
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/alz.70804
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Author Notes: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
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Summary: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. Highlights Diabetes mellitus (DM) was associated with lower odds of amyloid beta (Aβ) and phosphorylated tau (p-tau) pathology across clinical populations. DM was associated with total tau and medial temporal atrophy in cognitively normal individuals without Aβ pathology. DM may be associated with dementia through neurodegenerative pathways other than Alzheimer's disease.
Item Description:Online veröffentlicht: 30 Oktober 2025
Gesehen am 10.12.2025
Physical Description:Online Resource
ISSN:1552-5279
DOI:10.1002/alz.70804

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