Examining the Contribution of Diabetes and Obesity to Alzheimer's Disease

Brian Gordon, Ph.D.

Project Summary:

The objective of this proposal is to examine the influence obesity and diabetes have on Alzheimer’s disease (AD) risk and pathology. Epidemiological studies suggest that both obesity and diabetes increase the risk of developing dementia. It is unclear if these two conditions act directly on Alzheimer’s pathology, or rather represent comorbid pathology that act in parallel to Alzheimer’s disease.

 

In the current proposal, obesity will be quantified using body mass index (BMI) and metabolic health will be measured using levels of glucose, insulin, and glycated hemoglobin (HbA1c). The proposed project will relate these markers of health to the risk of developing dementia as well as in vivo biomarkers of AD pathology that include positron emission tomography (PET) measures of beta-amyloid deposition, structural atrophy assessed with magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) measures of both beta-amyloid and tau pathology. Analyses will examine the relationships between health factors and AD biomarkers using both cross-sectional and longitudinal data.

 

Based upon prior epidemiological work we hypothesize that increased obesity and worse metabolic health will predict an increased likelihood of being demented at baseline. When examining longitudinal data we predict that there will be a relationship such that at midlife, but not older age, greater obesity and worse metabolic health will be associated with a greater risk of developing AD dementia and elevated AD pathology. Secondary analyses will explore the interaction of health risk factors and the presence of the apolipoprotein ε4 allele that increases the risk of AD. Understanding the pathways through which these diabetes and obesity increase the risk of AD dementia is crucial in formulating an effective public health policy.

 

Public Health Relevance: The number of adults aged 65 and older is expected to increase to nearly 1 billion by 2030. With this dramatic increase in elderly individuals, there is a rising concern over the implications of a corresponding increase in the number of individuals suffering from dementia. The worldwide costs of dementia as estimated to already be over $156 billion, with this cost only increasing in the future. A number of health factors including obesity and diabetes are associated with an increased risk of developing Alzheimer’s disease. Prior work examining these factors has almost exclusively focused on behavioral and clinical measures. As a result it is unknown whether these risk factors represent parallel influences, which also influence cognition, or whether they act directly on Alzheimer’s disease pathology. This research will directly address these questions by relating obesity and diabetes to measures of Alzheimer’s pathology. Understanding the mechanism through which obesity and diabetes impact Alzheimer’s risk is critical for developing effective interventions and treatments to lower the incidence of dementia.