Obesity and Alzheimer's Disease

肥胖和阿尔茨海默病

• 批准号: 7036949
• 负责人: DEBORAH R. GUSTAFSON
• 金额: $ 6.44万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036949
• 关键词: Alzheimer' s disease; Scandinavian country; age difference; aging; angiotensin receptor; angiotensins; apolipoprotein E; blood lipid; blood pressure; body composition; body physical activity; catechol methyltransferase; dementia; disease /disorder etiology; disease /disorder onset; disease /disorder proneness /risk; epidemiology; genetic polymorphism; human data; longitudinal human study; miscellaneous oxidoreductase; obesity; peptidyl dipeptidase A; plasminogen activator; statistics /biometry; time resolved data

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.

描述（由申请人提供）：肥胖与阿尔茨海默病（AD）有关，尤其是女性。然而，在 AD 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，体重和体重指数的暂时变化可能不仅会影响AD风险，还会影响进展，并最终导致死亡。 BMI 在 AD 中的作用还强调了危险因素时机的重要性，无论是与疾病发作的关系还是它们是否发生在早年、中年还是晚年；并说明了在晚年某些时刻可能发生的危险因素与疾病关系方向的变化。该项目的目标是在三项基于人群的纵向研究中评估 BMI 以及相关血管和遗传因素与 AD 的关系，这些研究包含世界上无与伦比的与衰老精神疾病相关的流行病学、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 年间，他们的基线年龄为 38 岁至 70 岁，以及 95 岁。 2) 评估超重和肥胖在 AD 和其他痴呆症中的作用，考虑肥胖暴露的“关键期”、肥胖测量与痴呆发作之间的时间长度、当前超重和肥胖终点在痴呆症关系中的作用风险，并按年龄组检查风险因素，并考虑出生队列。 3) 评估与 AD 和其他痴呆症血管病因相关的遗传多态性的作用，及其与肥胖的潜在相互作用。 4) 考虑身体活动和其他血管危险因素，例如血压和血脂，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相关的生命历程将有助于未来设计基于年龄和既往体重模式的定制干预计划，并有助于评估更好的超重和肥胖终点，以优化最大年龄的健康组。