Adiposity, hyperinsulinemia, diabetes and Alzheimer's disease: an epidemiological perspective

Abstract

The objective of this manuscript is to provide a comprehensive review of the epidemiologic evidence linking the continuum of adiposity, hyperinsulinemia, and diabetes with Alzheimer's disease. The mechanisms for these associations remain to be elucidated, but may include direct actions from insulin, advanced products of glycosilation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of Alzheimer's disease. The evidence relating adiposity in old age to Alzheimer's disease is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance, is also related to a higher risk of Alzheimer's disease. Hyperinsulinemia is a risk factor for diabetes, and numerous studies have shown a relation of diabetes with higher Alzheimer's disease risk. Most studies fail the take into account the continuum linking these risk factors which may result in underestimation of their importance in Alzheimer's disease. The implication of these associations is that a large proportion of the world population may be at increased risk of Alzheimer's disease given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and diabetes. However, if proven causal, these associations also present a unique opportunity for prevention and treatment of Alzheimer's disease.

Figure

Natural history of the continuum of adiposity, insulin resistance, hyperinsulinemia, glucose intolerance and diabetes. Increased adiposity causes insulin resistance and hyperinsulinemia. Insulin levels may decrease over time due to pancreatic failure, resulting in glucose intolerance and diabetes. Adiposity, hyperinsulinemia, glucose intolerance and diabetes could increase brain amyloid beta deposition leading to Alzheimer’s disease individually or in aggregate in addition to causing cerebrovascular disease.