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P3‐134: Insulin metabolism and the risk of Alzheimer's disease: The Rotterdam Study
Author(s) -
Schrijvers Elisabeth,
Witteman Jacqueline C.M.,
Sijbrands Eric J.G.,
Hofman Albert,
Koudstaal Peter J.,
Breteler Monique M.B.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.1109
Subject(s) - insulin resistance , medicine , insulin , diabetes mellitus , rotterdam study , hazard ratio , endocrinology , population , type 2 diabetes , proportional hazards model , quartile , cohort , cohort study , confidence interval , environmental health
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.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.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.Our findings suggest that insulin metabolism influences the clinical manifestation of AD only within 3 years.