Carmelli D, DeCarli C, Swan G E, Kelly-Hayes M, Wolf P A, Reed T, Guralnik J M
Center for Health Sciences, SRI International, Menlo Park, California 94025, USA.
J Gerontol A Biol Sci Med Sci. 2000 Feb;55(2):M103-9. doi: 10.1093/gerona/55.2.m103.
Cognitive decline and poor physical function are risk factors for disability in old age and may occur more often in subjects with the apolipoprotein E epsilon4 (ApoE-epsilon4) allele. The objective of this study was to investigate the joint effect of ApoE-epsilon4 and structural changes detected on MRI brain scans on cognitive decline and lower-extremity function.
Brain MRI (1.5 T), neuropsychological tests, and lower-extremity physical function tests were administered to World War II male veteran twins ages 69 to 80. Quantification of MRI scans used a previously published algorithm to segment brain images into total cerebral brain (TCB), cerebrospinal fluid (CSF), and white-matter hyperintensity (WMH) volumes. A short battery of physical performance tests was used to assess lower-extremity function. Ten-year changes in performance on the Mini-Mental State Exam (MMSE), the Benton Visual Retention Test (BVRT), and the Digit Symbol Substitution (DSS) test were used to assess cognitive decline.
For the sample as a whole, the comparison of subjects by median split of total cerebral brain volume found that those with brain volumes below the median performed worse on tests of gait and balance (p < .01) and experienced greater cognitive decline on the MMSE and BVRT cognitive test batteries (both p < .01). In addition, subjects with WMH volumes above the median had poor performance on the standing balance tasks and experienced greater decline on the DSS test (p < .01). Stratified analyses revealed that the joint effect of radiological findings and the ApoE-epsilon4 allele on cognitive decline and lower-extremity function was often greater than that expected from the separate effects combined.
We conclude that radiological findings in conjunction with ApoE-epsilon4 may single out a group at higher risk for dementia. We speculate that the observed interaction effect may be due to increased susceptibility to brain injury or impaired repair mechanisms in subjects with ApoE-epsilon4.
认知功能衰退和身体功能不佳是老年残疾的风险因素，在载脂蛋白Eε4（ApoE-ε4）等位基因携带者中可能更常见。本研究的目的是调查ApoE-ε4与脑部MRI扫描检测到的结构变化对认知功能衰退和下肢功能的联合影响。
对69至80岁的二战男性退伍军人双胞胎进行脑部MRI（1.5T）、神经心理学测试和下肢身体功能测试。MRI扫描的定量分析使用先前发表的算法将脑图像分割为全脑总体积（TCB）、脑脊液（CSF）和白质高信号（WMH）体积。使用一组简短的身体性能测试来评估下肢功能。用简易精神状态检查表（MMSE）、本顿视觉保持测验（BVRT）和数字符号替换测验（DSS）的十年表现变化来评估认知功能衰退。
对于整个样本，按全脑总体积中位数分割对受试者进行比较发现，脑体积低于中位数的受试者在步态和平衡测试中表现更差（p <.01），在MMSE和BVRT认知测试组中认知功能衰退更严重（均p <.01）。此外，WMH体积高于中位数的受试者在站立平衡任务中表现不佳，在DSS测试中衰退更严重（p <.01）。分层分析显示，影像学结果和ApoE-ε4等位基因对认知功能衰退和下肢功能的联合影响通常大于单独效应之和的预期。
我们得出结论，影像学结果与ApoE-ε4相结合可能会筛选出患痴呆症风险较高的人群。我们推测，观察到的交互作用可能是由于ApoE-ε4携带者对脑损伤的易感性增加或修复机制受损所致。
