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

EMC Schrijvers, JCM Witteman, EJG Sijbrands… - Neurology, 2010 - AAN Enterprises
EMC Schrijvers, JCM Witteman, EJG Sijbrands, A Hofman, PJ Koudstaal, MMB Breteler
Neurology, 2010AAN Enterprises
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 …
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.
American Academy of Neurology