Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0948, USA.
Neuropsychology. 2013 Jul;27(4):391-401. doi: 10.1037/a0032707.
This study examined the impact of age and apolipoprotein E (APOE) genotype on the rate of cognitive decline in nondemented elderly participants in a simulated Alzheimer's disease (AD) primary prevention treatment trial carried out by the Alzheimer's Disease Cooperative Study.
Cognitive tests were administered at baseline and at four subsequent annual evaluations to 417 nondemented participants (172 men, 245 women) between the ages of 74 and 93 (M = 79.13 ± 3.34). APOE genotyping was available for 286 of the participants.
Four-year decline was evident on measures of orientation, memory, executive function, and language. Faster decline was evident in APOE ε4+ (a genetic risk factor for AD; n = 73) than in ε4- participants (n = 213), even after controlling for education, gender, ethnicity, and baseline functional and cognitive abilities. This discrepancy increased with age, indicating an Age × Genotype interaction.
These results are consistent with population-based studies, and extend the findings to a carefully screened sample that meets inclusion and exclusion criteria for an AD primary prevention trial. The interaction between age and APOE genotype on rate of decline suggests that preclinical disease may be overrepresented in older ε4+ individuals. Thus, APOE genotype and age should be considered in the design of AD primary prevention treatment trials.
本研究通过阿尔茨海默病合作研究（Alzheimer's Disease Cooperative Study）开展的模拟阿尔茨海默病（AD）一级预防治疗试验，考察了年龄和载脂蛋白 E（APOE）基因型对无痴呆老年参与者认知衰退速度的影响。
对 417 名年龄在 74 至 93 岁之间（M=79.13±3.34）的非痴呆参与者（172 名男性，245 名女性）进行了基线和随后的四次年度评估，测试了认知能力。286 名参与者可进行 APOE 基因分型。
在定向、记忆、执行功能和语言方面，四年内出现了明显的衰退。即使在控制了教育、性别、种族以及基线功能和认知能力后，APOE ε4+（AD 的遗传风险因素；n=73）参与者的衰退速度明显快于 ε4-参与者（n=213）。这种差异随着年龄的增长而增大，表明存在年龄与基因型的交互作用。
这些结果与基于人群的研究一致，并将研究结果扩展到一个经过精心筛选的样本，该样本符合 AD 一级预防试验的纳入和排除标准。衰退速度上的年龄与 APOE 基因型之间的相互作用表明，在年龄较大的 ε4+个体中，可能存在更多的临床前疾病。因此，在 AD 一级预防治疗试验的设计中，应考虑 APOE 基因型和年龄。
