We performed a systematic review and meta-analysis to explore whether type 2 diabetes mellitus (T2DM) increases the risk of Alzheimer's disease (AD). We also reviewed interactions with smoking, hypertension, and apolipoprotein E ɛ4. Using a series of databases (MEDLINE, EMBASE, PubMed, Current Contents Connect, and Google Scholar), we identified a total of 15 epidemiologic studies. Fourteen studies reported positive associations, of which 9 were statistically significant. Risk estimates ranged from 0.83 to 2.45. The pooled adjusted risk ratio was 1.57 (95% confidence interval: 1.41, 1.75), with a population-attributable risk of 8%. Smoking and hypertension, when comorbid with T2DM, had odds of 14 and 3, respectively. Of the 5 studies that investigated the interaction between T2DM and apolipoprotein E ɛ4, 4 showed positive associations, of which 3 were significant, with odds ranging from 2.4 to 4.99. The pooled adjusted risk ratio was 2.91 (95% confidence interval: 1.51, 5.61). Risk estimates were presented in the context of a key confounder-cerebral infarcts-which are more common in those with T2DM and might contribute to the manifestation of clinical AD. We provide evidence from clinico-neuropathologic studies that demonstrates the following: First, cerebral infarcts are more common than AD-type pathology in those with T2DM and dementia. Second, those with dementia at postmortem are more likely to have both AD-type and cerebrovascular pathologies. Finally, cerebral infarcts reduce the number of AD lesions required for the manifestation of clinical dementia, but they do not appear to interact synergistically with AD-type pathology. Therefore, the increased risk of clinically diagnosed AD seems to be mediated through cerebrovascular pathology.

中文翻译：

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2型糖尿病是阿尔茨海默氏病的危险因素：与此关系相关的混杂因素，相互作用和神经病理学。

我们进行了系统的综述和荟萃分析，以探讨2型糖尿病（T2DM）是否会增加阿尔茨海默氏病（AD）的风险。我们还回顾了与吸烟，高血压和载脂蛋白Eɛ4的相互作用。使用一系列数据库（MEDLINE，EMBASE，PubMed，Current Contents Connect和Google Scholar），我们总共确定了15项流行病学研究。十四项研究报告了正相关性，其中九项具有统计学意义。风险估计范围为0.83至2.45。汇总调整后风险比为1.57（95％置信区间：1.41、1.75），人群归因风险为8％。与T2DM合并时，吸烟和高血压的几率分别为14和3。在研究T2DM与载脂蛋白Eɛ4之间相互作用的5项研究中，有4项显示正相关，其中3个有效，赔率范围从2.4到4.99。合并调整后风险比为2.91（95％置信区间：1.51、5.61）。危险性评估是在关键的混杂因素-脑梗死的背景下提出的，这在患有T2DM的患者中更为常见，可能有助于临床AD的表现。我们从临床神经病理学研究中提供的证据表明：首先，在患有T2DM和痴呆症的患者中，脑梗死比AD型病理更常见。第二，死后患有痴呆症的人更可能同时患有AD型和脑血管疾病。最后，脑梗塞可减少临床痴呆表现所需的AD病变数量，但它们似乎与AD型病理学没有协同作用。所以，