Objective: To assess whether diabetes alone or in association with Apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer’s Disease (AD) diagnosis. Methods: A retrospective cohort study of 33,456 participants from the National Alzheimer’s Coordinating Center database. Results: Participants with one or two APOE ε4 alleles had 2.71 (CI:2.55–2.88) and 9.37 (CI:8.14–10.78) times higher odds of AD diagnosis, respectively, relative to those with zero ε4 alleles. In contrast, diabetic participants showed 1.07 (CI:0.96–1.18) times higher odds of AD relative to nondiabetics. Diabetes did not exacerbate the odds of AD in APOE ε4 carriers. APOE ε4 carriage was correlated with declines in long-term memory and verbal fluency, which were strongly correlated with conversion to AD. However, diabetes was correlated with working memory decline, which had a relatively weak correlation with AD. Conclusions: Unlike APOE ε4, there was little evidence that diabetes was a risk factor for AD.

目的：评估单独的糖尿病或与载脂蛋白 E (APOE) ε4 基因型相关的糖尿病是否会增加阿尔茨海默病 (AD) 诊断的风险。方法：对来自国家阿尔茨海默病协调中心数据库的 33,456 名参与者进行回顾性队列研究。结果：与具有零个 ε4 等位基因的参与者相比，具有一个或两个 APOE ε4 等位基因的参与者的 AD 诊断几率分别高 2.71 (CI:2.55–2.88) 和 9.37 (CI:8.14–10.78) 倍。相比之下，糖尿病参与者患 AD 的几率比非糖尿病参与者高 1.07 倍（CI：0.96-1.18）。糖尿病并不会加剧 APOE ε4 携带者患 AD 的几率。 APOE ε4 携带与长期记忆力和语言流畅性下降相关，而长期记忆力和语言流畅性又与 AD 的转化密切相关。然而，糖尿病与工作记忆下降相关，而工作记忆下降与 AD 的相关性相对较弱。结论：与 APOE ε4 不同，几乎没有证据表明糖尿病是 AD 的危险因素。