Obesity and Alzheimer's Disease

描述（由申请人提供）：肥胖与阿尔茨海默病（AD）有关，特别是在女性中。然而，在AD的整个进展过程中，体重和体重指数（BMI）的变化也有报道，导致低体重或低BMI预测患有该疾病的患者的死亡率。因此，体重和BMI的时间变化不仅可能影响AD风险，还可能影响疾病进展，最终导致死亡。BMI在AD中的作用还强调了风险因素发生时间的重要性，无论是与疾病发作的关系，还是它们是否发生在早期、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期的某些时间点。本项目的目标是在三项以人群为基础的纵向研究中评估BMI和相关血管和遗传因素与AD的关系，这些研究包含与世界上无与伦比的老年精神疾病相关的流行病学，临床和生物学数据。我们建议：1）在瑞典哥德堡进行的三项基于人群的研究中，描述超重和肥胖在女性和男性AD和其他痴呆症中的作用。这些研究的参与者出生于1901年至1930年之间，从基线年龄38至70岁和95岁进行了前瞻性随访。2)评估超重和肥胖在AD和其他痴呆中的作用，考虑肥胖暴露的“关键时期”，肥胖测量和痴呆发作之间的时间长度，当前超重和肥胖与痴呆风险的关系，以及按年龄组检查风险因素，并考虑出生队列。3)评估与AD和其他痴呆的血管病因相关的遗传多态性的作用，以及它们与肥胖的潜在相互作用。4)考虑体力活动和其他血管风险因素，如血压和血脂，以及它们与肥胖和遗传因素的潜在相互作用，以调节AD和其他痴呆症的风险。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制的干预计划，并有助于评估超重和肥胖的更好的终点，以优化最老年龄组的健康。

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.