Insulin metabolism and the risk of Alzheimer disease: The Rotterdam Study
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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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Epidemiological and clinical studies have suggested a link between type 2 diabetes and Alzheimer's disease.
“Epidemiological and clinical studies have suggested a link between type 2 diabetes and Alzheimer's disease [78].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [78]
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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.
- Venue
- Neurology
- Published
- 2010-11-30
- Volume
- 75
- Issue
- 22
- Pages
- 1982-1987
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- 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
- Health Sciences › Medicine › Physiology › 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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