Hofman A, Ott A, Breteler M M, Bots M L, Slooter A J, van Harskamp F, van Duijn C N, Van Broeckhoven C, Grobbee D E
Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, Netherlands.
Lancet. 1997 Jan 18;349(9046):151-4. doi: 10.1016/S0140-6736(96)09328-2.
Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimer's disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimer's disease. We investigated the frequency of dementia and its subtypes in relation to atherosclerosis and apolipoprotein E.
We did a population-based study of 284 patients with dementia, 207 of whom had Alzheimer's disease, and 1698 individuals who were not demented. Indicators of atherosclerosis included vessel wall thickness and plaques of the carotid arteries, assessed by ultrasonography, and the ratio of ankle-to-brachial systolic blood pressure as a measure of generalised atherosclerosis. Based on these indicators participants were scored from 0 (no atherosclerosis) to 3 (severe atherosclerosis) for degree of atherosclerosis. Apolipoprotein-E polymorphisms were assessed in 246 patients and in 928 controls.
All indicators of atherosclerosis were associated with dementia (odds ratios ranging from 1.3 to 1.9) and its major subtypes Alzheimer's disease (odds ratios 1.3-1.8) and vascular dementia (odds ratios 1.9-3.2). The frequencies of all dementia. Alzheimer's disease, and vascular dementia increased with the degree of atherosclerosis. The odds ratio for Alzheimer's disease in those with severe atherosclerosis compared with those without atherosclerosis was 3.0 (95% CI 1.5-6.0; p = 0.001). In participants with the apolipoprotein-E epsilon 4 genotype and an atherosclerosis score of 2 or 3 the odds ratio for all dementia was 4.5 (2.0-10.1; p < 0.001), for Alzheimer's disease was 3.9 (1.6-9.6; p = 0.002), and for vascular dementia was 19.8 (4.1-95.0; p < 0.001).
These findings suggest that dementia and its two major subtypes Alzheimer's disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein E and atherosclerosis in the aetiology of Alzheimer's disease.
血管疾病与痴呆症有关，但动脉粥样硬化是否与最常见的痴呆类型——阿尔茨海默病相关尚不清楚。载脂蛋白E基因型与阿尔茨海默病有关，我们推测它与动脉粥样硬化共同在阿尔茨海默病的病因中起作用。我们研究了痴呆症及其亚型与动脉粥样硬化和载脂蛋白E的关系。
我们对284例痴呆患者（其中207例患有阿尔茨海默病）和1698例非痴呆个体进行了一项基于人群的研究。动脉粥样硬化的指标包括通过超声检查评估的颈动脉血管壁厚度和斑块，以及踝臂收缩压比值作为全身性动脉粥样硬化的指标。根据这些指标，参与者的动脉粥样硬化程度评分为0（无动脉粥样硬化）至3（严重动脉粥样硬化）。对246例患者和928例对照进行了载脂蛋白E多态性评估。
动脉粥样硬化的所有指标均与痴呆症（比值比为1.3至1.9）及其主要亚型阿尔茨海默病（比值比为1.3 - 1.8）和血管性痴呆（比值比为1.9 - 3.2）相关。所有痴呆症、阿尔茨海默病和血管性痴呆的发生率均随动脉粥样硬化程度的增加而升高。与无动脉粥样硬化者相比，严重动脉粥样硬化者患阿尔茨海默病的比值比为3.0（95%可信区间为1.5 - 6.0；p = 0.001）。在载脂蛋白Eε4基因型且动脉粥样硬化评分为2或3的参与者中，所有痴呆症的比值比为4.5（(2.0 - 10.1；p < 0.001），阿尔茨海默病为3.9（1.6 - 9.6；p = 0.002），血管性痴呆为19.8（4.1 - 95.0；p < 0.001）。
这些发现表明，痴呆症及其两种主要亚型阿尔茨海默病和血管性痴呆与动脉粥样硬化有关，并且在阿尔茨海默病的病因中载脂蛋白E与动脉粥样硬化之间存在相互作用。
