The epidemiology of adiposity and dementia.

Adipose tissue is the largest endocrine gland in the body, yet only recently has its role in neurodegenerative disease been considered. Prospective population level evidence has emerged to show that both obesity and overweight, is associated with an increased risk of all cause dementia, Alzheimer's disease (AD), and underlying neurodegenerative changes. Weight loss in late life however is associated with dementia, and those categorized as underweight are also at a greater risk of dementia. Given the current epidemic of obesity, and the expected age-related increase in dementia incidence, even a small association between these two diseases has far reaching public health implications. However, due to the effects of both AD-associated weight loss and age-related changes in body composition, there are methodological challenges in appropriately evaluating obesity as a risk factor for developing dementia. There is a need to take a 'life course approach' and to consider the role of risk factors prior to the onset of old age. Our work has shown that both obesity and overweight, as measured by body mass index and skinfold thickness, in middle-age are strongly associated with an increased risk of all cause dementia, Alzheimer disease & Vascular dementia, independent of the development of diabetes and cardiovascular-related morbidities. There is also value in assessing regional body shape distributions of adiposity, particular the role of abdominal obesity. Mechanistic pathways such as adipocyte secreted proteins and hormones, and inflammatory cytokines could explain the association between obesity and increased risk of dementia.