Cited by 328Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsDiabetes, Cardiovascular Risks, and Lipoproteins

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Insulin metabolism and the risk of Alzheimer disease: The Rotterdam Study

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Schrijvers, E.M.C., Witteman, J.C.M., Sijbrands, E.J.G., Hofman, A., Koudstaal, P.J., Breteler, M.M.B.·2010·Neurology

DOI 10.1212/wnl.0b013e3181ffe4f6PMC PMC3014236

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Abstract

OBJECTIVE: Diabetes mellitus has been associated with an increased risk of Alzheimer disease (AD), but how it exerts its effect remains controversial. Possible pathophysiologic mechanisms are glucose toxicity and a direct effect of insulin on amyloid metabolism. Most studies had short follow-up, and longer-term effects of diabetes on AD risk are unknown. We investigated whether fasting glucose and insulin levels and insulin resistance are associated with the risk of AD and whether this risk is constant over time. METHODS: The study was based on 3,139 participants of the Rotterdam Study, a population-based cohort study. All subjects were free from dementia, did not have a history of diabetes, and had fasting levels of glucose and insulin measured at baseline. Insulin resistance was estimated with the homeostasis model assessment. We investigated how fasting glucose, insulin, and insulin resistance are related to the risk of AD in 3 different strata according to time-to-event, using Cox proportional hazards models. RESULTS: During follow-up, 211 participants developed AD, 71 of them within 3 years of baseline. Levels of insulin and insulin resistance were associated with a higher risk of AD within 3 years of baseline. After 3 years, the risk was no longer increased. Glucose was not associated with a higher risk of AD. There was no interaction of APOE ε4 carriership and insulin metabolism on the risk of AD. CONCLUSIONS: Our findings suggest that insulin metabolism influences the clinical manifestation of AD only within 3 years.

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Authors: Schrijvers, E. M. C., Witteman, J. C. M., Sijbrands, E. J. G., Hofman, A., Koudstaal, P. J., & Breteler, M. M. B.
Affiliations: Erasmus MC (NL)
From the Departments of Epidemiology (E.M.C.S., J.C.M.W., A.H., M.M.B.B.), Neurology (E.M.C.S., P.J.K.), and Internal Medicine (E.J.G.S.), Erasmus MC University Medical Center, Rotterdam, the Netherlands.
ORCID: Sijbrands, E.J.G.
Koudstaal, P.J.
Breteler, M.M.B.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2010-11-30
Volume: 75
Issue: 22
Pages: 1982-1987
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.0b013e3181ffe4f6
PMC: PMC3014236
OpenAlex: W2084979315
Cited by: 328
References: 40
Citations by year: 2026: 7 · 2025: 14 · 2024: 14 · 2023: 19 · 2022: 16 · 2021: 25 · 2020: 26 · 2019: 20 · 2018: 25 · 2017: 33 · 2016: 23 · 2015: 21 · 2014: 26 · 2013: 19 · 2012: 24
FWCI: 12.68
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Neurology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion)
Funders: National Institute on Aging (R01AG033193)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: Alzheimer's disease, insulin metabolism, insulin resistance, fasting insulin, fasting blood glucose, diabetes mellitus, APOE ε4, amyloid metabolism, glucotoxicity, disease onset timing, Rotterdam Study
MeSH terms: Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Blood Glucose, Female, Genotype, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Risk, Cohort Studies, Proportional Hazards Models, Apolipoprotein E4

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Insulin metabolism and the risk of Alzheimer disease: The Rotterdam Study

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