(12-12-10) Insulin metabolism and the risk of Alzheimer disease: The Rotterdam Study.

Schrijvers EM, Witteman JC, Sijbrands EJ, Hofman A, Koudstaal PJ, Breteler MM.

Department of Epidemiology, Erasmus MC University Medical Center, PO Box 2040,
3000 CA Rotterdam, the Netherlands [email protected].
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 ?4 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.

Source: Neurology. 2010 Nov 30;75(22):1982-7.

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