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（由适用提供）：90岁及以上的人（年龄最大）是美国人群中增长最快的部分，并且患有痴呆症率高，一种涉及记忆和其他与功能损失相关的思维问题的疾病。痴呆症与健康状况不佳，医疗保健成本不良以及护理人员，医疗保健系统和社会的严重燃烧有关。鉴定和治疗已经提出，用他汀类药物有效治疗的高胆固醇可能是痴呆症的可改变危险因素。目前尚不清楚高胆固醇和他汀类药物的使用是否受到90岁及以上患者发展痴呆症的保护或有害。这项90多个研究是一项大型基于人群的纵向研究，对年龄最大的老龄化。最近，我们发现，在最大的老年中使用他汀类药物与平均三年的痴呆发育发育的33％至57％显着相关，无论报道的高胆固醇病史如何。他汀类药物可能通过降低胆固醇的多种机制来对痴呆症风险作用，包括与痴呆症相关的异常β淀粉样蛋白斑和对血管事件的保护的产生受损。这是拟议的研究计划的目的是扩展我们以前的发现，并使用90+研究收集的数据评估了最古老的老年人使用他汀类药物使用与改善痴呆症风险之间关联的四个可能的解释。一种，某些或所有机制可能起到利用作用。 First, we will evaluate if the competing risk of mortality accounts for the association between statin use and improved dementia risk (Aim 1), We will then examine whether blood cholesterol levels measured at age 90+ account for the association between statin use and expanded dementia risk (Aim 2), which if true would suggest that statin use is associated with dementia-associated neuropathology (amyloid vs vascular), and If so whether neuropathology accounts对于他汀类药物使用和发育的痴呆症风险之间的关联（AIM 3）。最后，我们将使用脑成像（Florbetapir淀粉样蛋白PET和结构MRI和结构MRI）来评估他汀类药物的使用是否与痴呆症与痴呆症相关的神经病理学相关，如果是的，则使用哪种类型的神经病理学（在MRI上测量的PET或血管测量的淀粉样蛋白（AIM 4）。了解他汀类药物在最古老的人群中如何使痴呆症风险受益可能对在这一迅速增长的人群中的心血管危险因素的管理中具有重要的公共卫生影响。