Obesity is associated with Alzheimer's disease (AD), particularly in women. However, changes in body weight and body mass index (BMI) throughout the progressive course of AD have also been reported, resulting in a low body weight or low BMI predicting mortality among those who have the disease. Thus, temporal changes in body weight and BMI may not only influence AD risk, but also progression, and ultimately death. The role of BMI in AD also underscores the importance of timing of risk factors, both in relationship to disease onset and whether they occur in early-, mid-, or late-life; and illustrates the change in direction of risk factor-disease relationships that may occur at certain points in late life. The goals of this project are to evaluate the role of BMI and related vascular and genetic factors in relationship to AD in three population-based, longitudinal studies containing epidemiologic, clinical, and biologic data related to psychiatric disorders of aging that are unsurpassed in the world. We propose to: 1) Characterize the role of overweight and obesity in AD and other dementias in women and men across three population-based studies in Goteborg, Sweden. Participants in these studies, born between 1901 and 1930, have been followed prospectively from baseline ages of 38 to 70, and 95 years. 2) Evaluate the role of overweight and obesity in AD and other dementias with consideration for 'critical periods' of adiposity exposure, the length of time between an adiposity measurement and onset of dementia, the role of current overweight and obesity outpoints in relationship to dementia risk, and examination of risk factors by age group with consideration for birth cohort. 3) Assess the role of genetic polymorphisms related to the vascular etiology of AD and other dementias, and their potential interaction with obesity. 4) Consider physical activity and other vascular risk factors, such as blood pressure and blood lipids, and their potential interaction with obesity and genetic factors to modulate risk for AD and other dementias. Understanding the life course of overweight and obesity in relationship to dementia will assist the future design of tailor-made intervention programs based on age and previous weight patterns, and assist in the evaluation of better outpoints for overweight and obesity that optimize health in the oldest age groups. ? ?
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