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

Year: 2025

Type: article

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. 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.

Source: Alzheimer s & Dementia

Institutions: Maastricht University, Amsterdam Neuroscience, Amsterdam UMC Location Vrije Universiteit Amsterdam, Fundacion CITA Alzheimer, Charles University, University Hospital in Motol, Centre Hospitalier Universitaire Vaudois, Hôpital Orthopédique de la Suisse Romande, University of Eastern Finland, Vrije Universiteit Brussel, University of Antwerp, Universitair Ziekenhuis Brussel, University of Zurich, University Hospital Zurich, Psychiatrische Universitätsklinik Zürich, Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, Hospital de Sant Pau, Biomedical Research Networking Center on Neurodegenerative Diseases, University of Gothenburg, Aristotle University of Thessaloniki, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Universitair Ziekenhuis Leuven, KU Leuven, Karolinska Institutet, Heidelberg University, Central Institute of Mental Health, Sahlgrenska University Hospital, UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, Institute Born-Bunge, UCB Pharma (Belgium), Warneford Hospital, University of Oxford, Radboud University Nijmegen, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, University of Bologna, Institut de Recerca Biomèdica Catalunya Sud, Universitat Rovira i Virgili, Bellvitge University Hospital, Institut d'Investigació Biomédica de Bellvitge, Centro de Investigación Biomédica en Red, Universitat de Barcelona, Aarhus University, Lundbeck Foundation

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,200

Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, European Federation of Pharmaceutical Industries and Associations, University College London, European Commission, ZonMw, Generalitat de Catalunya, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Hjärnfonden, Vetenskapsrådet, UK Dementia Research Institute, Olav Thon Stiftelsen, Selfridges Group Foundation, Horizon 2020 Framework Programme, HORIZON EUROPE Framework Programme

Awards: G1088883541, G1307999793, G1451607819, G150733400, G1546555014, G1588116593, G1613806636, G1771944843, G1798618210, G1802301745, G1833008592, G1928552717, G1938858119, G196098375, G201353144, G2074436950, G237833635, G2475953241, G2501976640, G2543812357, G3041725664, G3107890091, Fluid biomarkers for neurodegenerative dementias, G3719620581, G3842727039, European platform for neurodegenerative disorders, G4166693258, G4244943609, G4260843567, Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions, G432431387, G4377393254, G4704820683, G4786159458, European Prevention of Alzheimer’s Dementia Consortium, G4937468798, Prevention and Remediation of Insulin Multimorbidity in Europe, G506008078, G516766298, Fluid biomarkers for neurodegenerative dementias, G574669212, G5778058681, G5985173317, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G6207287561, G6445013291, G6470304958, G6544145387, G663896020, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6701856265, G6745400708, G691317373, European Prevention of Alzheimer's Dementia Consortium Data & Sample Access, G7075164165, G7293611571, G7461077622, G8782684654

OpenAlex ID: W4415694461