Wu Z, Kinslow C, Pettigrew K D, Rapoport S I, Schapiro M B
Laboratory of Neurosciences, National Institute on Aging, Bethesda, Maryland 20892, USA.
Alzheimer Dis Assoc Disord. 1998 Sep;12(3):190-7. doi: 10.1097/00002093-199809000-00011.
Whereas early-onset Alzheimer disease (AD; usually onset at age < 50 years) has been defined with genetic mutation on chromosomes 1, 14, and 21, the degree of familial contribution to late-onset AD is unclear. Further, it is uncertain if subgroups of late-onset AD exist. To examine the influence of familial factors as a function of age in late-onset AD we investigated lifetime risks and age-specific hazard rates of AD-like illness among late-onset AD probands' and controls' first-degree relatives, using questionnaires and medical records. As part of a longitudinal study on aging and AD, we studied 78 AD probands with age of onset > or =50 years (28 "definite" and 50 "probable" AD according to NINCDS/ADRDA criteria) and 101 healthy old controls seen since 1981. Both probands and controls were screened rigorously with medical tests and brain imaging and seen regularly until autopsy. Multiple informants and medical records were used for first-degree relatives. Among first-degree relatives, 49 secondary cases of AD-like illness were found for the AD probands' relatives (391 relatives 40 years old or older) compared with 20 cases among controls' relatives (456 relatives 40 years old or older). Relatives of AD probands had a significantly increased lifetime risk of AD-like illness of 52.8+/-11.4% by age 94 years compared with a lifetime risk in relatives of controls of 22.1+/-5.8% by age 90 years. Age-specific hazard rates in relatives of AD probands increased until the 75-79-year age interval and then decreased; in contrast the age-specific hazard rates increased in relatives of controls after the 80-84-year age interval. To determine if a dividing line exist among late-onset AD, several cutoff ages were used in our study to compare cumulative risk curves of AD-like illness between relatives of late-onset probands and relatives of late-late-onset probands. Differences in the pattern of cumulative incidence of AD in relatives showed that 67-71 years is the range for a dividing line between late- and late-late-onset AD. Age-specific hazard rates of AD in relatives supported a difference between late- and late-late-onset. Whereas these rates increased until the 75-79-year age interval and then decreased in late-onset AD, the rates began increasing after the 65-69-year age interval and through the oldest age interval in both late-late-onset AD and control groups. Our results support the concept that familial factors exist in late-onset AD and that different familial factors may exist in late-onset AD subgroups.
早发性阿尔茨海默病（AD；通常发病年龄＜50岁）已被定义为与1号、14号和21号染色体上的基因突变有关，而家族因素对晚发性AD的影响程度尚不清楚。此外，晚发性AD是否存在亚组也不确定。为了研究家族因素在晚发性AD中随年龄的作用，我们通过问卷调查和医疗记录，调查了晚发性AD先证者和对照者的一级亲属中类似AD疾病的终生风险和年龄特异性发病率。作为一项关于衰老与AD的纵向研究的一部分，我们研究了78名发病年龄≥50岁的AD先证者（根据NINCDS/ADRDA标准，28例“确诊”AD和50例“可能”AD）以及自1981年以来观察的101名健康老年对照者。先证者和对照者均经过严格的医学检查和脑成像筛查，并定期随访直至尸检。一级亲属的情况通过多名信息提供者和医疗记录来确定。在一级亲属中，AD先证者的亲属中有49例出现类似AD疾病的继发病例（391名40岁及以上的亲属），而对照者亲属中有20例（456名40岁及以上的亲属）。与90岁时对照者亲属22.1±5.8%的终生风险相比，AD先证者的亲属到94岁时类似AD疾病的终生风险显著增加，为52.8±11.4%。AD先证者亲属的年龄特异性发病率在75 - 79岁年龄段之前上升，之后下降；相比之下，对照者亲属的年龄特异性发病率在80 - 84岁年龄段之后上升。为了确定晚发性AD中是否存在分界线，我们在研究中使用了几个临界年龄来比较晚发性先证者亲属和极晚发性先证者亲属中类似AD疾病的累积风险曲线。AD在亲属中累积发病率模式的差异表明，67 - 71岁是晚发性和极晚发性AD之间的分界线范围。亲属中AD的年龄特异性发病率支持了晚发性和极晚发性AD之间的差异。在晚发性AD中，这些发病率在75 - 79岁年龄段之前上升，之后下降，而在极晚发性AD和对照组中，发病率在65 - 69岁年龄段之后开始上升，并贯穿最高年龄组。我们的结果支持这样的概念，即家族因素存在于晚发性AD中，并且晚发性AD亚组中可能存在不同的家族因素。
