Adiposity and Alzheimer's disease

Abstract

The objective of this manuscript is to provide a comprehensive review of the relation between adiposity and Alzheimer's disease (AD), its potential mechanisms, and issues in its study. Adiposity represents the body fat tissue content. When the degree of adiposity increases it can be defined as being overweight or obese by measures such as the body mass index. Being overweight or obese is a cause of hyperinsulinemia and diabetes, both of which are risk factors for AD. However, the epidemiologic evidence linking the degree of adiposity and AD is conflicting. Traditional adiposity measures such as body mass index have decreased validity in the elderly. Increased adiposity in early or middle adult life leads to hyperinsulinemia which may lead to diabetes later in life. Thus, the timing of ascertainment of adiposity and its related factors is critical in understanding how it might fit into the pathogenesis of AD. We believe that the most plausible mechanism relating adiposity to AD is hyperinsulinemia, but it is unclear whether specific products of adipose tissue also have a role. Being overweight or obese is increasing in children and adults, thus understanding the association between adiposity and AD has important public health implications.

Figure 1

Correlation between the construct of adiposity, body mass index (and the NHLBI classification), and waist circumference.

Figure 2

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, and glucose intolerance and diabetes ensue. Hypothetically, high insulin levels and then diabetes related processes could increase brain amyloid beta deposition leading to Alzheimer’s disease. It is unclear when this process starts, but it could begin in early adulthood or even childhood. As depicted in the figure, these factors change with time, and the timing of their ascertainment may affect findings in epidemiological and clinical studies.

Figure 3

Hazard ratios relating quartiles (Q) of body mass index (BMI) to Alzheimer’s disease in persons < 76 years old and persons ≥ 76 years old, adjusting for age, sex, years of education, ethnic group, and APOEɛ4. Only the HR for the 3^rd and 4th quartiles in persons < 76 years were statistically significant. The Washington Heights Inwood Columbia Aging Project, 1992–2003.

Figure 4

Hazard ratios [16] relating quartiles (Q) of waist circumference (WC) to Alzheimer’s disease in persons < 76 years old and persons ≥ 76 years old, adjusting for age, sex, years of education, ethnic group, and APOEɛ4. The HR for the 4^th Q of WC and the p for trend in persons < 76 years were statistically significant. The Washington Heights Inwood Columbia Aging Project, 1992–2003.