血浆β淀粉样蛋白水平与认知功能衰退的关系

The plasma level of amyloid-β is associated with cognitive decline: a two years follow-up study in Xi′an rural areas

目的在西安市农村人群队列中观察基线时血浆β淀粉样蛋白(Aβ)水平与随访2年后认知功能变化的关系。方法2014年10月—2015年3月对西安市鄠邑区曲抱村40岁以上常住人群进行面对面问卷调查,应用简易精神状态量表(MMSE)评估整体认知功能,采用双抗体夹心酶联免疫法(ELISA)测定血浆Aβ浓度。2年后再次进行面对面问卷调查,观察基线时血浆Aβ水平与MMSE得分变化的关系。结果2年后共随访到1 020例,其中MMSE得分下降(下降≥2分)者为223例(21.9%)。与MMSE得分无变化(下降<2分)组相比,MMSE得分下降组的年龄更大(P<0.001),文化程度更低(P<0.001),而两组间性别、高血压病史、高脂血症史、糖尿病史、携带APOE ε4等位基因等的差异均无统计学意义。单因素方差分析显示,基线Aβ1-40水平较低组MMSE得分下降小于Aβ1-40中等水平组(P=0.012),但Aβ1-42不同水平组、Aβ1-42/Aβ1-40比值不同水平组间的MMSE得分变化的差异无统计学意义(P=0.758,P=0.671)。多因素logistic回归分析显示,基线血浆Aβ1-40低水平组的MMSE得分下降较慢(OR=0.565,95%CI 0.379~0.845,P=0.005);不同血浆Aβ1-42水平及不同Aβ1-42/Aβ1-40比值组间,MMSE得分下降的差异均无统计学意义。结论在40岁以上认知功能正常人群中,基线血浆Aβ1-40水平较低时,认知功能衰退较慢,但尚需长期随访、动态观察血浆Aβ变化进一步证实。

Objective To explore the relationship between plasma amyloid-β(Aβ) and cognitive decline during 2 year follow-up in a population-based cohort in Xi′an rural areas. Methods The study was conducted in Qubao village in Xi′an suburbs cognitively normal residents over 40 years old were recruited from October 2014 to March 2015 and given a face-to-face standardized interview. Mini-mental state examination (MMSE) was employed to evaluate the global cognitive function, and quantification of plasma Aβ was measured by sandwich enzyme-linked immunosorbent assay (ELISA) at baseline. Two years later, MMSE was tested at the end of study. Then logistic regression was performed to analyze the relationship between baseline Aβ and cognitive change during 2 year follow-up. Results A total of 1 020 participants completed the study, among whom 223 subjects (21.9%) presented MMSE scores decline (defined as MMSE scores decreased ≥2 points). Compared with those without decline, participants in the MMSE decline group were older (P<0.001) and had lower education level (P<0.001), while gender, hypertension, hyperlipemia, diabetes mellitus and APOE genotype were not significantly different between two groups. One-way analysis of variance (ANOVA) showed that the MMSE score decline was slighter in the lower tertile of baseline Aβ1-40 compared with middle tertile (P=0.012), while MMSE decline were similar between different Aβ1-42 level groups and Aβ1-42/Aβ1-40 ratio groups (P=0.758, P=0.671, respectively). Multivariable logistic regression analysis showed that MMSE scores in the lower baseline plasma Aβ1-40 level declined more slowly (OR=0.565, 95%CI 0.379-0.845, P=0.005). However, the MMSE decline were also similar among different baseline plasma Aβ1-42 levels groups and Aβ1-42/Aβ1-40 ratio groups. Conclusion Population with lower level of baseline plasma Aβ1-40 manifests lower cognitive decline during 2 years, however further investigation on dynamics of plasma Aβ and long term follow up are needed.