From Inserm (L.C., P.-Y.S.), CESP Centre for Research in Epidemiology and Population Health, UMR-S1018, Hormones and Cardiovascular Disease, University Paris Sud, Villejuif; Hôpital Bicêtre (S.B.-T., A.G.-M.), APHP, Service de Génétique moléculaire, Pharmacogénétique et Hormonologie Kremlin-Bicêtre; Inserm UMR-S693 (S.B.-T., A.G.-M.), Université Paris Sud 11, Kremlin-Bicêtre; Inserm U1061 (M.-L.A.), Université Montpellier 1, Montpellier; CMMR CHU Dijon (O.R.), Dijon; Université Victor Segalen Bordeaux 2 (J.-F.-D.), Bordeaux; and Inserm U897 (J.-F.D.), Epidemiology and Neuropsychology of Brain Aging, Bordeaux, France.
Neurology. 2014 Feb 11;82(6):504-11. doi: 10.1212/WNL.0000000000000107. Epub 2014 Jan 29.
We aimed to investigate the impact of endogenous estradiol (E2) on dementia and to evaluate the contribution of vascular risk factors and inflammatory and blood coagulation markers to this association.
Using data from a French population-based prospective study (the Three-City Study) including 5,644 postmenopausal women aged 65 years or older, we investigated the association of endogenous total-E2 and bioavailable-E2 and total-testosterone with the 4-year incidence of all-cause dementia. We further focused on the role of dementia and cardiovascular risk factors as well as inflammation (C-reactive protein, fibrinogen) and hypercoagulability (fibrin d-dimers, thrombin generation) in these associations. We used a case-cohort design consisting of a random subcohort of 562 women not using hormone therapy and 132 incident dementia cases.
Adjusted Cox proportional hazards models showed a J-shaped relationship between total-E2 and risk of dementia (p = 0.001). Total-E2 values in the lower and upper quartiles were associated with an increased dementia risk (adjusted hazard ratio [HR] [95% confidence interval] = 2.2 [1.1-4.5] and HR = 2.4 [1.2-5.2], respectively). Importantly, the risk associated with higher E2 levels was dramatically increased in women with diabetes compared with nondiabetic women (adjusted HR associated with the upper E2 quartile = 14.2 [1.60-123] and HR = 3.4 [0.1-147], respectively, p interaction <0.05). Similar results were found for bioavailable-E2. Adjustment for inflammatory and blood coagulation markers did not modify our results. No significant association was found for total-testosterone.
High E2 level is an independent predictor of incident dementia, particularly in postmenopausal women with diabetes.
本研究旨在探讨内源性雌二醇（E2）对痴呆的影响，并评估血管危险因素以及炎症和血液凝固标志物对这种关联的贡献。
我们利用一项基于法国人群的前瞻性研究（Three-City 研究）的数据，该研究纳入了 5644 名年龄在 65 岁及以上的绝经后妇女，调查了内源性总-E2 和生物可利用-E2 与总睾酮与所有原因痴呆的 4 年发生率之间的关联。我们进一步关注痴呆和心血管危险因素以及炎症（C 反应蛋白、纤维蛋白原）和高凝状态（纤维蛋白二聚体、凝血酶生成）在这些关联中的作用。我们使用了病例-队列设计，包括一个未使用激素治疗的 562 名随机亚队列和 132 例新发痴呆病例。
调整后的 Cox 比例风险模型显示，总-E2 与痴呆风险之间呈 J 形关系（p = 0.001）。总-E2 值处于较低和较高四分位数的女性痴呆风险增加（调整后的危险比[HR] [95%置信区间] = 2.2 [1.1-4.5]和 HR = 2.4 [1.2-5.2]）。重要的是，与较高 E2 水平相关的风险在患有糖尿病的女性中明显高于非糖尿病女性（与上四分位数 E2 相关的调整 HR = 14.2 [1.60-123]和 HR = 3.4 [0.1-147]，分别，p 交互<0.05）。对于生物可利用-E2 也得到了类似的结果。调整炎症和血液凝固标志物并未改变我们的结果。总睾酮与痴呆无显著相关性。
高 E2 水平是痴呆发生的独立预测因子，特别是在患有糖尿病的绝经后妇女中。
