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APOE ε4在调节老年人认知功能衰退其他风险因素的作用方面。

The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.

作者信息

Haan M N, Shemanski L, Jagust W J, Manolio T A, Kuller L

机构信息

Department of Epidemiology and Preventive Medicine, University of California, School of Medicine, Davis 95616, USA.

出版信息

JAMA. 1999 Jul 7;282(1):40-6. doi: 10.1001/jama.282.1.40.

Abstract

CONTEXT

Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD.

OBJECTIVES

To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline.

DESIGN

The Cardiovascular Health Study, a population-based, prospective cohort study.

SETTING AND POPULATION

A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively.

MAIN OUTCOME MEASURES

Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus.

RESULTS

Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele.

CONCLUSIONS

Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.

摘要

背景

老年人认知能力下降往往是痴呆症的早期预测指标。亚临床心血管疾病(CVD)和糖尿病可能导致老年人认知功能大幅下降。这些风险可能会因载脂蛋白E(APOE)基因型与CVD危险因素或亚临床CVD之间的基因-环境相互作用而改变。

目的

研究亚临床CVD与老年人认知功能下降之间的关联,并研究APOE基因型对亚临床疾病与认知下降之间关联的效应修正作用。

设计

心血管健康研究,一项基于人群的前瞻性队列研究。

设置与人群

共5888名从加利福尼亚州萨克拉门托县、北卡罗来纳州福赛斯县、马里兰州华盛顿县和宾夕法尼亚州匹兹堡随机选取的符合医疗保险条件的参与者,年龄在65岁及以上,于1989 - 1990年(n = 5201)和1992 - 1993年(n = 687)招募,分别随访7年和5年。

主要观察指标

改良简易精神状态检查表和数字符号替换测试的分数随时间的变化,作为APOE基因型、亚临床CVD和糖尿病的函数。

结果

70%的参与者在改良简易精神状态检查表上没有明显下降。收缩压、踝臂指数、颈内动脉粥样硬化、糖尿病以及几种常见CVD诊断与改良简易精神状态检查表和数字符号替换测试的分数下降显著相关。任何APOE ε4等位基因的存在会增加与外周血管疾病、颈总动脉和颈内动脉粥样硬化或糖尿病相关的认知下降率。

结论

大多数健康老年人未经历认知下降。亚临床CVD指标是认知下降的适度预测指标。携带任何APOE ε4等位基因且合并动脉粥样硬化、外周血管疾病或糖尿病的人群比不携带APOE ε4等位基因或无亚临床CVD的人群认知下降风险显著更高。高水平的动脉粥样硬化独立于APOE基因型增加认知下降。

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