Hyperinsulinemia and risk of Alzheimer disease

Objective: To explore the association between fasting insulin levels and dementia. Methods: Fasting insulin levels were measured from frozen sera using solid-phase chemiluminescent enzyme immunoassay in a sample of elderly subjects chosen at random from a cohort of persons aged 65 years and older from northern Manhattan. Dementia was diagnosed using standard methods. Neuropsychiatric testing was available on all subjects at each follow-up interval. Results: A total of 683 subjects without prevalent dementia were followed for 3,691 person-years and 149 persons developed dementia ( 137 Alzheimer disease [ AD], 6 dementia associated with stroke, 6 other). The risk of AD doubled in the 39% of the sample with hyperinsulinemia (HR = 2.1; 95% CI: 1.5, 2.9) and was highest in people without diabetes. The HR relating presence of hyperinsulinemia or diabetes in 50% of our sample to AD was 2.2 ( 95% CI: 1.5, 3.1). The risk of AD attributable to the presence of hyperinsulinemia or diabetes was 39%. The HR of AD for the highest quartile of insulin compared to the lowest was 1.7 ( 95% CI: 1.0, 2.7; p for trend = 0.009). Hyperinsulinemia was also related to a significant decline in memory-related cognitive scores, but not to decline in other cognitive domains. Conclusions: Hyperinsulinemia is associated with a higher risk of AD and decline in memory.