Clinical Management Unit, Alto Deba Hospital, Avenida Navarra 16, Mondragon, 20500 Spain ; Health Services Research on Chronic Patients Network (REDISSEC), Avenida Navarra 16, Mondragon, 20500 Spain.
Health Services Research on Chronic Patients Network (REDISSEC), Avenida Navarra 16, Mondragon, 20500 Spain ; AP-OSI Research Unit, Alto Deba Hospital, Avenida Navarra 16, Mondragon, 20500 Spain.
Alzheimers Res Ther. 2015 Jan 15;7(1):2. doi: 10.1186/s13195-014-0079-9. eCollection 2015.
Recent research on biomarkers has made possible the diagnosis of pre-dementia and even preclinical Alzheimer's disease (AD), thus providing the ideal context for prevention. The aim of this study was to investigate the epidemiology of the early stages of AD by fitting neuropathologic and epidemiological data to assess the feasibility of prevention programs.
The study addressed primarily the construction of a discrete event simulation model of the stages of dementia. Age was included in the mathematical functions to combine the two competitive risks that determine the epidemiology of AD, that is, time to onset of dementia and time until death by other causes. Subsequently, this model was calibrated to reproduce the prevalence of pathological findings associated with AD. The beginning of the preclinical stage was taken to coincide with Thal phase 1 deposition of amyloid-beta. The duration of the prodromal stage, marked by mild cognitive impairment, was based on a 10% annual conversion rate from this level of impairment to dementia. The validation of prevalence figures also permitted estimation of the incidence and duration of preclinical and prodromal stages.
In Spain, half of the nearly 10 million people aged more than 60 years are in the early stages of AD; 35.9% are in a preclinical stage, and up to 14.2% are in a prodromal stage. However, dementia will develop in only 38% of this population. The weighted mean time to dementia was 22.0 years from the start of Thal phase 1 and 9.0 years from the start of phase 2. Results of simulation models showed a lack of correlation between clinical and pathological classifications.
These findings raise questions about the feasibility of drug-based prevention strategies. Currently, screening programs with biomarkers in the early stages of AD cannot be applied to the half of the general population older than 60 years. Hence, intensive research is needed regarding risk factors, so that more affordable strategies may be planned. More efficient criteria are also needed to select those subjects with mild cognitive impairment who have an increased probability of positive screening for biomarkers (prodromal stage).
最近关于生物标志物的研究使得痴呆前甚至临床前阿尔茨海默病（AD）的诊断成为可能，从而为预防提供了理想的契机。本研究旨在通过拟合神经病理学和流行病学数据来评估预防计划的可行性，以调查 AD 早期阶段的流行病学。
该研究主要涉及构建痴呆症各阶段的离散事件模拟模型。年龄被纳入数学函数中，以结合决定 AD 流行病学的两个竞争性风险，即痴呆发作的时间和因其他原因死亡的时间。随后，该模型经过校准以再现与 AD 相关的病理性发现的流行率。将临床前阶段的开始时间设定为淀粉样β蛋白 Thal 阶段 1 沉积的时间。前驱期的持续时间，以轻度认知障碍的 10%年转化率为标志，从这一认知障碍水平发展为痴呆症。流行率数据的验证还允许估计临床前和前驱期的发病率和持续时间。
在西班牙，近 1000 万 60 岁以上的人群中，有一半处于 AD 的早期阶段；35.9%处于临床前阶段，多达 14.2%处于前驱期。然而，只有 38%的人群会发展为痴呆症。从 Thal 阶段 1 开始到痴呆症的加权平均时间为 22.0 年，从阶段 2 开始到痴呆症的加权平均时间为 9.0 年。模拟模型的结果显示，临床和病理分类之间缺乏相关性。
这些发现引发了关于基于药物的预防策略可行性的问题。目前，AD 早期阶段的生物标志物筛查计划不能应用于一半以上的 60 岁以上的普通人群。因此，需要对风险因素进行深入研究，以便制定更经济实惠的策略。还需要更有效的标准来选择那些轻度认知障碍患者，这些患者进行生物标志物（前驱期）筛查的阳性可能性增加。
