Carmelli D, Swan G E, Reed T, Miller B, Wolf P A, Jarvik G P, Schellenberg G D
Center for Health Sciences, SRI International, Menlo Park, CA 94025, USA.
Neurology. 1998 Jun;50(6):1580-5. doi: 10.1212/wnl.50.6.1580.
To investigate the combined effect of the apolipoprotein E epsilon4 (ApoE*4) allele and midlife cardiovascular risk factors on cognitive decline.
Data are from the National Heart, Lung, and Blood Institute Twin Study-a longitudinal cardiovascular epidemiologic study of World War II male veteran twins currently in its 27th year of follow-up. Subjects were assessed for cardiovascular risk factors, including BP and glucose levels, at mean ages 48, 58, and 63 years. Participants in the current study are 410 individual twin subjects for whom cognitive function was measured twice, at ages 63 and 73 years. Ten-year change scores in performance on neuropsychological test examinations were adjusted for age, education, baseline score, and incident cardiovascular disease.
For the sample as a whole, we observed a significant decline (p < 0.01) in cognitive performance over the 10 years of follow-up. ApoE4 carriers with midlife hyperglycemia experienced the greatest decline in performance, which was also greater than expected from the separate effects combined. Midlife hypertension and ApoE4, were each associated with excess decline in performance on tests of psychomotor speed. Their joint effect, however, was not greater than expected from the separate effects combined.
ApoE4 and midlife cardiovascular risk factors may have a synergistic effect on decline in cognitive function. This effect may be due to greater vascular or degenerative damage among subjects with ApoE4.
研究载脂蛋白Eε4（ApoE*4）等位基因与中年心血管危险因素对认知功能衰退的联合影响。
数据来自美国国立心肺血液研究所双胞胎研究——一项针对二战男性退伍军人双胞胎的纵向心血管流行病学研究，目前已进行到第27年随访。在平均年龄48岁、58岁和63岁时对受试者进行心血管危险因素评估，包括血压和血糖水平。本研究的参与者为410名个体双胞胎受试者，在63岁和73岁时对其认知功能进行了两次测量。对神经心理测试成绩的10年变化分数进行了年龄、教育程度、基线分数和心血管疾病发病情况的校正。
对于整个样本，我们观察到在10年的随访中认知表现有显著下降（p<0.01）。中年高血糖的ApoE4携带者表现下降最大，且大于单独效应合并后的预期值。中年高血压和ApoE4均与心理运动速度测试成绩的过度下降有关。然而，它们的联合效应并不大于单独效应合并后的预期值。
ApoE4和中年心血管危险因素可能对认知功能衰退有协同作用。这种效应可能是由于ApoE4携带者中更大的血管或退行性损伤所致。
