To use survival modeling to estimate disease duration in autosomal dominant familial Alzheimer disease (ADAD) and ascertain whether factors influencing age at onset also affect survival.

Symptomatic mutation carriers (201 presenilin 1 [PSEN1] and 55 amyloid precursor protein [APP]) from ADAD families referred to the Dementia Research Centre, between 1987 and 2019, were included. Survival was assessed with respect to age at onset, year of birth, APOE 4 status, cognitive presentation, and sex using multilevel mixed-effects Weibull survival models. The contribution of mutation and family to variance in age at onset and duration was also assessed.

Estimated mean survival was 11.6 (10.4–12.9) years and was similar for APP and PSEN1 mutations. Sixty-seven percent of the variance in age at onset was explained by mutation and 72% by mutation and family together. In contrast, only 6% of the variance in disease duration was explained by mutation specificity and 18% by family membership. Irrespective of gene, survival appeared longer for successive generations and in individuals with atypical presentations. Older age at onset was associated with longer duration within PSEN1 and shorter duration within APP mutation carriers. No differences in survival time were found between sexes or between mutations located before or beyond codon 200 within PSEN1.

Survival is influenced by mutation to a much lesser extent than age at onset. Survival time has increased over time and is longer in atypical presentations. These insights may inform the interpretation of disease-modifying therapy trials in ADAD.

使用生存模型估计常染色体显性家族性阿尔茨海默病 (ADAD) 的疾病持续时间，并确定影响发病年龄的因素是否也会影响生存。

包括 1987 年至 2019 年间来自 ADAD 家族的症状性突变携带者（201 个早老素 1 [ PSEN1 ] 和 55 个淀粉样前体蛋白 [ APP ]），这些突变携带者被提交给痴呆症研究中心。使用多级混合效应 Weibull 生存模型评估生存年龄、出生年份、APOE 4 状态、认知表现和性别。还评估了突变和家庭对发病年龄和持续时间变化的贡献。

估计的平均生存期为 11.6（10.4-12.9）年，APP和PSEN1突变相似。67% 的发病年龄差异由突变解释，72% 由突变和家庭共同解释。相比之下，疾病持续时间的差异只有 6% 由突变特异性解释，18% 由家庭成员解释。无论基因如何，连续几代和具有非典型表现的个体的存活时间似乎更长。发病年龄越大，PSEN1持续时间越长， APP突变携带者持续时间越短。未发现性别之间或位于PSEN1内密码子 200 之前或之后的突变之间的存活时间差异。

与发病年龄相比，突变对生存的影响程度要小得多。生存时间随着时间的推移而增加，并且在非典型表现中更长。这些见解可能会为 ADAD 中疾病修饰治疗试验的解释提供信息。