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

摘要 阿尔茨海默病和相关痴呆症(ADRD)在任何年龄都是一种压倒性的医学状况，但 青壮年的ADRD尤其具有破坏性，会影响个人的生活质量和独立性 在他们的黄金年华。早发性ADRD(EOD)被定义为65岁之前的ADRD诊断。虽然它是 通常认为EOD主要作为一种罕见的遗传综合征发生，已知的遗传变异解释 对于不到5%的病例。尽管在大多数情况下，这种疾病的病程令人痛苦，性质不清楚 在案例中，对爆炸性爆炸的研究普遍不足。目前关于排泄物的流行和发病率的数据似乎 低估了问题的严重性，并且没有关于诱因和/或 EOD的保护性因素。 利用国际痴呆症风险共享项目(DRPP)的基础设施，我们提出了一个前瞻性的 基于五大多民族人群队列个体的排爆发展研究 研究(ARIC、MESA、FHS、白厅II和英国生物库)。这项研究提供了(1)改进的机会 事件爆炸事件的估计，(2)调查心血管、生活方式和行为危险因素在 EOD的发病和(3)研究在存在遗传易感性的情况下是否存在有利的中年风险概况 延迟排泄物的发病年龄。这项评估将是第一项汇集多个国际人口的研究 在中青年人群中前瞻性研究65岁前ADRD的队列。当前的观念 EOD仅仅是由基因综合征驱动的，这给识别明显的诱因和/或 EOD的保护性因素和针对易感人群的早期发现和预防。调查结果 将揭示爆炸性爆炸的脆弱性和独特的风险因素，并可能导致发展 制定更有效的预防目标，以延缓疾病的发生和发展。排爆相对较少，而且 因此，初级和初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战略，重点放在原始 和初级预防。

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.