Obesity and Alzheimer's Disease

描述(申请人提供)：肥胖与阿尔茨海默病(AD)有关，尤其是在女性中。然而，也有报道称，在阿尔茨海默病进展过程中，体重和体重指数(BMI)的变化，导致低体重或低BMI预测疾病患者的死亡率。因此，体重和BMI的时间变化不仅可能影响AD的风险，而且还可能影响进展，最终导致死亡。体重指数在阿尔茨海默病中的作用也强调了风险因素的时机的重要性，无论是与疾病发病的关系，还是发生在生命早期、中期或晚期；并说明了风险因素-疾病关系的方向变化，可能发生在晚年的某些时间点。该项目的目标是在三项以人群为基础的纵向研究中评估BMI以及相关的血管和遗传因素与AD的关系，这些研究包含了与世界上无与伦比的老龄化精神障碍有关的流行病学、临床和生物学数据。我们建议：1)通过瑞典哥德堡的三项基于人群的研究，描述超重和肥胖在AD和其他痴呆症中的作用。这些研究的参与者出生在1901年至1930年之间，他们被前瞻性地跟踪调查，基线年龄从38岁到70岁，以及95岁。2)评估超重和肥胖在阿尔茨海默病和其他痴呆症中的作用，考虑肥胖暴露的“关键时期”，从肥胖测量到痴呆症发病之间的时间长度，当前超重和肥胖在痴呆症风险中的作用，以及考虑出生队列的年龄组对风险因素的检查。3)评估与AD和其他痴呆的血管病因学相关的基因多态性的作用，以及它们与肥胖的潜在交互作用。4)考虑体力活动和其他血管危险因素，如血压和血脂，以及它们与肥胖和遗传因素的潜在交互作用，以调节AD和其他痴呆的风险。了解超重和肥胖与痴呆症的关系，将有助于未来根据年龄和以前的体重模式设计量身定做的干预计划，并有助于评估更好的超重和肥胖点，以优化最年长年龄段的健康。

DESCRIPTION (provided by applicant): 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.