Apolipoprotein E ε4 allele genotype and the effect of depressive symptoms on the risk of dementia in men
Apolipoprotein E ε4 allele genotype and the effect of depressive symptoms on the risk of dementia in men
复制标题
DOI：
10.1001/archpsyc.65.8.906
复制
发表时间：
2008-08-01
影响因子：
--
通讯作者：
White, Lon R.
中科院分区：
文献类型：
--
作者：
Irie, Fumiko;Masaki, Kamal H.;White, Lon R.
背景：载脂蛋白 E e4 (APOE e4) 等位基因是阿尔茨海默病的遗传风险因素。最近，抑郁症也被认为是痴呆症的危险因素。然而，APOE 基因型对抑郁症和痴呆症之间关联的可能影响尚未得到检验。目的：检查抑郁症和 APOE e4 对痴呆症及其亚型风险的独立和综合影响。设计：檀香山-亚洲老龄化研究，一项针对日裔美国男性的基于人群的前瞻性队列研究。背景和参与者：抑郁症状和 APOEe4 等位基因的存在在 1991 年 3 月至 1993 年 10 月期间进行了评估1932 名 71 至 90 岁认知健康的男性。在大约 6 年的随访期间，根据 2 次重复检查的神经学评估（1994 年 4 月至 1996 年 4 月和 1997 年 10 月至 1999 年 2 月）诊断出痴呆症病例。 主要结果指标：总体痴呆、阿尔茨海默病和血管性痴呆。 结果：在分析模型中，抑郁症和 APOE e4 的相互作用具有统计学显着性。与既没有 APOE e4 也没有抑郁症的男性相比，患有 APOE e4 的非抑郁男性患痴呆症的风险并不显着（风险比，1.1；95% 置信区间 [CI]，0.6-1.8）；然而，没有 APOE e4 的抑郁男性患痴呆症的风险高出 1.6 倍（95% CI，0.8-3.0），而患有 APOE e4 的抑郁男性患痴呆症的风险高出 7.1 倍（95% CI，3.0-16.7）。对于亚型，我们发现阿尔茨海默病的风险也有类似的增加。结论：APOE e4 状态改变了老年男性抑郁症状与痴呆之间的关联。由于具有抑郁症状和 APOE e4 等位基因的个体患痴呆症的风险显着增加，因此人们可能要特别注意 APOE e4 等位基因也呈阳性的患有抑郁症的老年人的痴呆早期迹象。由于该队列仅包括男性，因此需要对女性进行进一步调查。
Context: The apolipoprotein E e4 ( APOE e4) allele is a genetic risk factor for Alzheimer disease. Recently, depression has also become recognized as a risk factor for dementia. However, the possible effect of the APOE genotype on the association between depression and dementia is unexamined.Objective: To examine the independent and combined effects of depression and APOE e4 on the risk of dementia and its subtypes.Design: The Honolulu- Asia Aging Study, a populationbased prospective cohort study of Japanese American men.Settings and Participants: Depressive symptoms and presence of theAPOEe4 allele were assessed between March 1991 and October 1993 in 1932 cognitively healthy men aged 71 to 90 years. Incident cases of dementia were diagnosed during approximately 6 years of follow- up based on neurologic assessment at 2 repeated examinations ( April 1994- April 1996 and October 1997- February 1999).Main Outcome Measures: Overall dementia, Alzheimer disease, and vascular dementia.Results: The interaction of depression and APOE e4 was statistically significant in the analytical models. Compared with men with neither APOE e4 nor depression, the risk of dementia in nondepressed men with APOE e4 was not significant ( hazard ratio, 1.1; 95% confidence interval [ CI], 0.6- 1.8); however, depressed men without APOE e4 had a 1.6- fold greater risk ( 95% CI, 0.8- 3.0), whereas depressed men with APOE e4 had a 7.1- fold greater risk ( 95% CI, 3.0- 16.7) of dementia. For subtypes, we found similar increased risks of Alzheimer disease.Conclusions: The APOE e4 status modifies the association between depressive symptoms and dementia in elderly men. Because individuals with depressive symptoms and the APOE e4 allele had a markedly increased risk of dementia, one might be especially watchful for early signs of dementia in the older person with depression who is also positive for the APOE e4 allele. Because this cohort includes only men, further investigation in women is required.