Early Onset Alzheimer's Disease and Related Dementias: A Population-Based Approach to Identify Characteristics and Risk Factors

早发性阿尔茨海默氏病和相关痴呆症：基于人群的特征和危险因素识别方法

基本信息

批准号：
10659338
负责人：
Sanaz Sedaghat
金额：
$ 76.87万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-15 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659338
关键词：
Adult Affect Age Age Years Age of Onset Alcohol consumption Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Behavioral Blood Pressure Blood Vessels Body mass index Cardiovascular system Characteristics Clinical Cognitive Cohort Studies Craniocerebral Trauma Data Development Diabetes Mellitus Diagnosis Disease Disease Progression Distress Early Diagnosis Early Onset Alzheimer Disease Education Eligibility Determination Epidemiology Evaluation Event Frontotemporal Dementia General Population Genes Genetic Genetic Predisposition to Disease Genetic Risk Health behavior Heart Diseases High Prevalence Hypertension Incidence Individual Infrastructure International Intervention Late Onset Alzheimer Disease Lewy Body Dementia Life Style Light Lipids Measures Medical Mental Depression Nature Participant Patients Persons Physical activity Physiological Population Population Study Predisposing Factor Predisposition Prevalence Prevention Prevention strategy Primary Prevention Prospective Studies Quality of life Race Renal function Reporting Risk Risk Factors Role Sample Size Secondary Prevention Smoking Social isolation Stroke Symptoms Syndrome Testing Time Variant Vascular Dementia Vulnerable Populations Woman biobank burden of illness cardiovascular health cardiovascular risk factor cohort data harmonization dementia risk demographics early onset genetic variant high risk human old age (65+)insight lifestyle factors middle age multi-ethnic non-genetic polygenic risk score population based presenilin-1 presenilin-2 protective factors rare variant screening sex stroke incidence tertiary prevention trend young adult

项目摘要

Summary Alzheimer's Disease and Related Dementias (ADRD) is an overwhelming medical condition at any age, but ADRD in younger adulthood is particularly devastating, affecting quality of life and independence of individuals in their prime years. Early onset ADRD (EOD) is defined as an ADRD diagnosis before age 65. While it is commonly perceived that EOD occurs primarily as a rare genetic syndrome, the known genetic variants account for less than 5% of cases. Despite the distressing course and unclear nature of the disease in the majority of cases, EOD is widely understudied. Current data on the prevalence and incidence of EOD seem to underestimate the magnitude of the problem and there is no information available regarding predisposing and/or protective factors for EOD. Using the infrastructure of an international Dementia Risk Pooling Project (DRPP), we propose a prospective study of EOD development which comprises individuals from five large multi-ethnic population-based cohort studies (ARIC, MESA, FHS, Whitehall II and, UK Biobank). This study provides the opportunity to (1) refine estimates of incident EOD, (2) investigate the role of cardiovascular, lifestyle and behavioral risk factors in the onset of EOD and (3) study whether a favorable midlife risk profile in the presence of genetic predisposition delays EOD age of onset. This evaluation will be the first study to pool multiple international population-based cohorts to prospectively study ADRD before the age of 65 in young and middle-aged adults. The current notion that EOD is merely driven by genetic syndromes has shadowed efforts to identify distinct predisposing and/or protective factors for EOD and targeting vulnerable populations for early detection and prevention. The findings will shed much needed light on the vulnerability and unique risk factors for EOD and may lead to development of more effective targets for prevention to delay onset and progression of disease. EOD is relatively rare and thus primordial and primary prevention may be more efficient than screening and secondary or tertiary prevention. Our data on EOD risk factors will strengthen targeted intervention strategies with focus on primordial and primary prevention.

概括阿尔茨海默氏病和相关痴呆症 (ADRD) 在任何年龄段都是一种压倒性的疾病，但是 ADRD 在成年早期尤其具有破坏性，影响生活质量和个人的独立性在他们的黄金年华。早发性 ADRD (EOD) 被定义为 65 岁之前诊断出 ADRD。人们普遍认为 EOD 主要是一种罕见的遗传综合症，已知的遗传变异说明少于 5% 的案例。尽管大多数人的疾病病程令人痛苦且性质不明确在这种情况下，EOD 得到了广泛的研究。目前有关 EOD 流行率和发生率的数据似乎低估问题的严重性，并且没有关于诱发和/或 EOD 的保护因素。利用国际痴呆症风险共担项目 (DRPP) 的基础设施，我们提出了一个前瞻性的 EOD 发展研究，包括来自五个大型多种族人群队列的个体研究（ARIC、MESA、FHS、Whitehall II 和英国生物银行）。这项研究提供了（1）改进的机会事件 EOD 的估计，(2) 调查心血管、生活方式和行为危险因素在事件中的作用 EOD 的发生和 (3) 研究在存在遗传倾向的情况下是否存在有利的中年风险状况延迟 EOD 发病年龄。这项评估将是第一项汇集多个国际人口的研究队列对 65 岁之前的年轻人和中年人进行前瞻性研究 ADRD。目前的观念 EOD 仅仅由遗传综合征驱动，这掩盖了识别不同诱因和/或 EOD 的保护因素并针对弱势群体进行早期发现和预防。研究结果将揭示 EOD 的脆弱性和独特风险因素，并可能带来发展制定更有效的预防目标，以延缓疾病的发生和进展。 EOD 相对罕见因此，原始和一级预防可能比筛查和二级或三级预防更有效预防。我们关于 EOD 风险因素的数据将加强有针对性的干预策略，重点关注原始和一级预防。