Silverman Jeremy M, Ciresi Gregory, Smith Christopher J, Marin Deborah B, Schnaider-Beeri Michal
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Arch Gen Psychiatry. 2005 May;62(5):565-73. doi: 10.1001/archpsyc.62.5.565.
The role of genetic factors in Alzheimer disease (AD) varies across the late life span, complicating efforts to quantify the risk of AD for relatives of probands with AD.
To visualize the changing levels of familial risk according to proband onset age and the age of the at-risk relative and to determine the familiality of age at onset in AD.
A retrospective, informant-based family study. SETTING, PATIENTS, AND OTHER PARTICIPANTS: Siblings and parents of probands with AD (relatives = 4687; probands = 904), ascertained at geriatric clinic and nursing home settings, and of elderly probands without dementia (relatives = 7649; probands = 1525) who were spouses of probands, participants at senior centers, or nursing home residents without dementia.
Informant-based assessments of AD in the relatives were used to generate 3-dimensional surfaces representing the patterns of risk of AD across the late life span depending on the specific onset age of the proband with AD (or assessment age of the elderly proband without dementia). We then constructed a 3-dimensional, age-specific, 10-year hazard rate ratio (HRR) surface representing the relative risk of AD in relatives of probands with AD with smoothly shifting levels of onset age compared with relatives of elderly probands without dementia.
The HRR surface peaked (HRR, 13.0) for younger sexagenarian relatives related to probands with AD with onset age in their early 60s. The HRRs dropped sharply both as the proband age at onset and the age of the relative increased. For relatives aged in their late 80s, the HRR fell lower than 2.0 regardless of proband onset age and their lower-limit 95% confidence intervals were less than 1.0.
The role of genetic risk factors decreases with increasing onset age of the proband with AD regardless of the age of the relatives themselves. The familiality of onset age is greatly reduced at later ages. The role of environmental risk factors in AD likely increases with onset age.
遗传因素在阿尔茨海默病（AD）中的作用在晚年阶段有所不同，这使得量化AD先证者亲属患AD风险的工作变得复杂。
根据先证者发病年龄和高危亲属的年龄，直观呈现家族风险水平的变化，并确定AD发病年龄的家族聚集性。
一项基于信息提供者的回顾性家族研究。
地点、患者及其他参与者：在老年诊所和养老院确定的AD先证者的兄弟姐妹及父母（亲属 = 4687人；先证者 = 904人），以及无痴呆的老年先证者的亲属（亲属 = 7649人；先证者 = 1525人），这些无痴呆的老年先证者是先证者的配偶、老年中心的参与者或养老院居民。
基于信息提供者对亲属中AD的评估，生成三维曲面，以呈现晚年阶段AD风险模式，该模式取决于AD先证者的特定发病年龄（或无痴呆老年先证者的评估年龄）。然后，构建一个三维、特定年龄的10年风险率比（HRR）曲面，以表示与无痴呆老年先证者的亲属相比，AD先证者亲属中AD的相对风险，其中AD先证者的发病年龄水平呈平滑变化。
与发病年龄在60岁出头的AD先证者相关的年轻六七十岁亲属的HRR曲面达到峰值（HRR为13.0）。随着先证者发病年龄和亲属年龄的增加，HRR均急剧下降。对于80多岁晚期的亲属，无论先证者发病年龄如何，HRR均降至低于2.0，其95%置信区间下限小于1.0。
无论亲属自身年龄如何，AD先证者发病年龄越大，遗传风险因素的作用越小。发病年龄的家族聚集性在晚年大大降低。AD中环境风险因素的作用可能随发病年龄增加而增加。
