Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?
Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?
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DOI：
10.1212/wnl.46.3.641
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发表时间：
1996-03-01
期刊：
影响因子：
9.9
通讯作者：
Farrer, LA
中科院分区：
文献类型：
--
作者：
Lautenschlager, NT;Cupples, LA;Farrer, LA
尽管最近在阿尔茨海默氏病（AD）的分子遗传学方面取得了进展，但有关疾病风险的几个基本问题尚未解决，即孟德尔因素是否导致了疾病的发生，以及AD是否是衰老过程的必然结果。这项研究旨在解决这些问题和其他方面的家庭聚集性疾病。在参与阿尔茨海默病遗传流行病学多机构研究（MINUS）项目的13个中心确定了1，694名符合可能或明确AD诊断标准的患者的连续样本。使用生存分析程序估计了12，971名一级亲属的不同阶层中AD的终生风险和发病年龄。到96岁时，一级亲属中AD的终生风险为39.0% +/- 2.1%。AD的特定风险在90岁后下降，数据集包括61名明显未受影响的人，他们活到96岁，没有患痴呆症。在所有年龄段，女性亲属患AD的风险均高于男性亲属。到80岁时，夫妻AD夫妇的儿童的累积风险为54%，是受影响母亲或父亲的儿童风险总和的1.5倍，是正常父母儿童风险的近5倍。受影响父亲的子女的累积风险是受影响母亲的子女的1.4倍。在早发性和晚发性家庭的风险评估，使用各种策略来确定年龄截止，产生了相互矛盾的结果。这些数据表明：（1）亲属间的终生患病风险不支持AD的简单常染色体显性遗传模式;（2）女性先天性比男性更易患AD;（3）男性遗传性病例的比例可能高于女性;（4）在缺乏生物学标记的情况下，区分早发和晚发型AD几乎没有意义;（5）AD的风险在90岁以后降低;（6）AD因此可能不是衰老过程的必然伴随物，这一结论对基础和应用AD研究具有深远的意义。从这项研究中得出的年龄和性别特异性终身风险是足够强大的，是一个可靠的信息来源，为咨询AD患者的亲属。
Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early-onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific Lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.