阿尔茨海默病的临床前、前驱和痴呆阶段的持续时间与年龄、性别和 APOE 基因型有关。
Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype.
机构信息
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
出版信息
Alzheimers Dement. 2019 Jul;15(7):888-898. doi: 10.1016/j.jalz.2019.04.001. Epub 2019 Jun 1.
INTRODUCTION
We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration.
METHODS
We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration.
RESULTS
The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE ε4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage.
DISCUSSION
Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design.
简介
我们评估了阿尔茨海默病（AD）的临床前期、前驱期和痴呆期的特定年龄持续时间，以及性别、环境、载脂蛋白 E（APOE）基因型和脑脊液 tau 对疾病持续时间的影响。
方法
我们在 6 个队列（n=3268）的合并样本中进行了多状态建模，以死亡为终末阶段，并估计了临床前期、前驱期和痴呆期的持续时间。
结果
AD 的总持续时间在 24 年（60 岁）至 15 年（80 岁）之间变化。对于出现临床前期 AD 的个体，在 70 岁时，估计的临床前期 AD 持续时间为 10 年，前驱期 AD 持续 4 年，痴呆期 AD 持续 6 年。男性、临床环境、APOE ε4 等位基因携带和异常脑脊液 tau 与较短的持续时间相关，这些影响取决于疾病阶段。
讨论
如果考虑年龄、性别、环境、APOE 和脑脊液 tau，AD 疾病持续时间的估计会更加准确。这将与临床实践和试验设计有关。
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