Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alzheimers Dement. 2010 Sep;6(5):404-11. doi: 10.1016/j.jalz.2010.02.003.
Patients with amnestic mild cognitive impairment (MCI) demonstrate decline in everyday function. In this study, we investigated whether whole brain atrophy and apolipoprotein E (APOE) genotype are associated with the rate of functional decline in MCI.
Participants were 164 healthy controls, 258 MCI patients, and 103 patients with mild Alzheimer's disease (AD), enrolled in the Alzheimer's Disease Neuroimaging Initiative. They underwent brain MRI scans, APOE genotyping, and completed up to six biannual Functional Activities Questionnaire (FAQ) assessments. Random effects regressions were used to examine trajectories of decline in FAQ across diagnostic groups, and to test the effects of ventricle-to-brain ratio (VBR) and APOE genotype on FAQ decline among MCI patients.
Rate of decline in FAQ among MCI patients was intermediate between that of controls and mild AD patients. Patients with MCI who converted to mild AD declined faster than those who remained stable. Among MCI patients, increased VBR and possession of any APOE varepsilon4 allele were associated with faster rate of decline in FAQ. In addition, there was a significant VBR by APOE varepsilon4 interaction such that patients who were APOE varepsilon4 positive and had increased atrophy experienced the fastest decline in FAQ.
Functional decline occurs in MCI, particularly among patients who progress to mild AD. Brain atrophy and APOE varepsilon4 positivity are associated with such declines, and patients who have elevated brain atrophy and are APOE varepsilon4 positive are at greatest risk of functional degradation. These findings highlight the value of genetic and volumetric MRI information as predictors of functional decline, and thus disease progression, in MCI.
遗忘型轻度认知障碍（MCI）患者的日常功能下降。在这项研究中，我们调查了全脑萎缩和载脂蛋白 E（APOE）基因型是否与 MCI 患者的功能下降速度有关。
参与者包括 164 名健康对照者、258 名 MCI 患者和 103 名轻度阿尔茨海默病（AD）患者，他们均来自阿尔茨海默病神经影像学倡议。他们接受了脑部 MRI 扫描、APOE 基因分型，并完成了多达六次的半年度功能活动问卷（FAQ）评估。使用随机效应回归来检查诊断组之间 FAQ 下降的轨迹，并测试脑室-脑比率（VBR）和 APOE 基因型对 MCI 患者 FAQ 下降的影响。
MCI 患者 FAQ 的下降速度在对照组和轻度 AD 患者之间处于中间水平。从 MCI 转为轻度 AD 的患者比保持稳定的患者下降速度更快。在 MCI 患者中，VBR 增加和携带任何 APOE ε4 等位基因与 FAQ 下降速度加快有关。此外，VBR 和 APOE ε4 之间存在显著的相互作用，即 APOE ε4 阳性且萎缩增加的患者在 FAQ 上的下降速度最快。
MCI 患者会出现功能下降，尤其是那些进展为轻度 AD 的患者。脑萎缩和 APOE ε4 阳性与这种下降有关，而那些脑萎缩程度较高且 APOE ε4 阳性的患者则处于功能退化的最大风险之中。这些发现突出了遗传和容积 MRI 信息作为 MCI 患者功能下降和疾病进展预测因子的价值。
