High adiposity: risk factor for dementia and Alzheimer's disease?

Higher levels of total and central adiposity, measured as higher body mass index (BMI) (in kilograms per square meter), waist circumference, or waist-to-hip ratio, have been associated with late-onset Alzheimer's disease (AD). However, some epidemiologic studies do not support this association, and potential underlying biological mechanisms that provide biological plausibility are not clear in terms of providing direct links to adipose tissue. Studies linking adiposity to AD have considered adiposity measures from mid-life and late-life. Given an evolving background trajectory of BMI that exists over the life course and the influence of dementia processes on BMI, results have been conflicting depending on when BMI is measured in relationship to clinical AD onset. This has made interpretation of the BMI-AD literature difficult. This debate will briefly review the epidemiologic evidence for and against an association between higher adiposity and AD, issues of timing of the adiposity measure in relation to AD onset, potential biological mechanisms for observed associations, and explanations for conflicting evidence.