Statins and Dementia in the Oldest-old

他汀类药物与老年人的痴呆症

• 批准号: 8912237
• 负责人: Marcella Evans
• 金额: $ 4.36万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912237
• 关键词: Accounting; Actins; Affect; Age; Aged, 80 and over; Aging; Amyloid; Autopsy; Blood; Blood Vessels; Brain; Brain imaging; Caregiver Burden; Caregivers; Cerebrum; Cholesterol; Data; Data Analyses; Dementia; Development; Disease; Epidemiology; Event; Family; Goals; Health; Health Care Costs; Healthcare Systems; Image; Incidence; Life; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medical History; Memory; Methods; Outcome; Participant; Pathology; Patients; Pharmaceutical Preparations; Play; Population; Positron-Emission Tomography; Production; Public Health; Quality of life; Recording of previous events; Reporting; Research; Risk; Risk Factors; Role; Senile Plaques; Serum; Societies; Thinking; United States; age group; aged; brain health; cardiovascular risk factor; case control; cerebrovascular; cohort; follow-up; functional loss; hazard; high risk; modifiable risk; mortality; neuropathology; non-demented; population based; prevent; public health relevance

 DESCRIPTION (provided by applicant): People aged 90 years and older (the oldest-old) are the fastest growing segment of the U.S. population and suffer from high rates of dementia, a disease involving memory and other thinking problems associated with functional loss. Dementia is associated with poor health outcomes and high health care costs, as well as a heavy burden on caregivers, the health care system, and society. Identification and treatment of modifiable risk factors of dementia is essential to ease the coming public health crisis particularly in the rapidly growing age group of the oldest-old. It has been suggested that high cholesterol, effectively treated with statin medications, may be a modifiable risk factor of dementia. It is unclear if high cholesterol and statin use is protective or detrimental towards developing dementia in people aged 90 years and older. The 90+ Study is a large population-based longitudinal study of aging and dementia in the oldest-old. Recently, we found that statin use in the oldest-old is significantly associated with a 33% to 57% decrease in development of dementia over an average of three years, regardless of reported history of high cholesterol. Statins may be acting on dementia risk through a variety of mechanisms beyond cholesterol-lowering, including impaired production of the abnormal beta amyloid plaques associated with dementia and protection against vascular events. Thus, the goal of the proposed research plan is to extend our previous findings and evaluate four possible explanations for the association between statin use and decreased dementia risk in the oldest-old, using data collected by The 90+ Study. It is possible that one, some, or all mechanism may play an explanatory role. First, we will evaluate if the competing risk of mortality accounts for the association between statin use and decreased dementia risk (Aim 1), which if true would suggest that statin use is not the true explanation behind the previous finding. We will then examine whether blood cholesterol levels measured at age 90+ account for the association between statin use and decreased dementia risk (Aim 2), which if true would suggest that statins are actin by cholesterol-lowering. We will use autopsy data to determine if statin use is associated with dementia-associated neuropathology (amyloid vs vascular), and if so whether neuropathology accounts for the association between statin use and decreased dementia risk (Aim 3). Last, we will use brain imaging (florbetapir amyloid PET and structural MRI and) to evaluate if statin use is associated with dementia- associated neuropathology in living participants and if so, what type of neuropathology (amyloid measured on PET or vascular measured on MRI) (Aim 4). Understanding how statin use benefits dementia risk in the oldest-old may have important public health implications for the management of cardiovascular risk factors in relation to brain health in this rapidly growing segment of the population.

 描述（由申请人提供）：90 岁及以上的人（最年长的老人）是美国人口增长最快的群体，患有痴呆症的比例很高，这种疾病涉及与功能丧失相关的记忆和其他思维问题。痴呆症与不良的健康结果和高昂的医疗费用以及对护理人员、医疗保健系统和社会的沉重负担有关，识别和治疗痴呆症的可改变危险因素对于缓解即将到来的公共卫生危机至关重要，特别是在当前的公共卫生危机中。迅速地有人认为，用他汀类药物有效治疗的高胆固醇可能是痴呆症的一个可改变的危险因素。目前尚不清楚高胆固醇和他汀类药物的使用是否能预防或损害人们患痴呆症。 90 岁以上老年人的研究是一项针对老年人的老龄化和痴呆症的大型纵向研究，最近我们发现，他汀类药物的使用与老年人的 33% 至 57% 显着相关。发育下降无论有报道的高胆固醇史如何，他汀类药物可能通过降低胆固醇以外的多种机制来降低痴呆风险，包括与痴呆相关的异常β淀粉样斑块的产生受损和预防血管疾病。因此，拟议研究计划的目标是利用 90 岁以上研究收集的数据，扩展我们之前的发现，并评估他汀类药物的使用与老年人痴呆风险降低之间的关联的四种可能的解释。那一个、一些或全部首先，我们将评估死亡的竞争风险是否可以解释他汀类药物的使用和痴呆风险降低之间的关联（目标 1），如果为真，则表明他汀类药物的使用并不是先前情况背后的真正解释。然后，我们将检查 90 岁以上测量的血液胆固醇水平是否可以解释他汀类药物的使用与痴呆风险降低之间的关联（目标 2），如果属实，则表明我们将使用他汀类药物来降低胆固醇。尸检数据以确定他汀类药物的使用是否与痴呆相关的神经病理学（淀粉样蛋白与血管性）相关，如果是，神经病理学是否可以解释他汀类药物的使用与痴呆风险之间的关联（目标 3），我们将使用脑成像（氟贝他淀粉样蛋白）。 PET 和结构 MRI 以及）评估他汀类药物的使用是否与活着的参与者的痴呆相关神经病理学相关，如果是，则是什么类型的神经病理学（通过 PET 或 PET 测量的淀粉样蛋白） MRI 测量的血管）（目标 4）。了解他汀类药物的使用如何有益于老年人的痴呆风险，可能对管理这一快速增长的人口群体中与大脑健康相关的心血管危险因素具有重要的公共卫生意义。