While the apolipoprotein E 4 allele (ApoE-4) is related to cognitive and brain decline in the general population, its effect on the brain in type 1 diabetes mellitus (T1DM) remains unclear. Therefore, the aim was to determine the interaction between ApoE-4 and T1DM on cognitive performance and hippocampal structure and connectivity as the brain area most vulnerable to ApoE-4 effects in adult patients with T1DM.

Blood sampling was performed in 104 patients with T1DM and 49 control subjects for ApoE genotyping, neuropsychology, and neuroimaging to determine hippocampal volume and resting-state connectivity. The interaction between T1DM status and ApoE-4 presence was investigated and adjusted for age and mean systolic blood pressure.

ApoE genotyping could not be performed for three patients with T1DM. Significant interaction effects, indicating a differential effect of ApoE-4 between both groups, were found for overall cognitive functioning and for the subdomains of information processing speed and attention. Additionally, interaction effects were present for right hippocampal connectivity with the right posterior cingulate and supramarginal gyri. Subsequent group analysis showed that patients with T1DM with ApoE-4 performed worse on these cognitive domains with increased connectivity, relative to their counterparts without ApoE-4. In contrast, no cognitive effects, but decreased connectivity, were observed in control subjects with ApoE-4. In patients with T1DM, higher right hippocampus connectivity with the posterior cingulate gyrus was related to poorer overall cognitive functioning.

The results may suggest that ApoE-4 presence leaves our patients with T1DM more susceptible to cognitive decrements at a younger age, possibly through vascular pathways, warranting further longitudinal studies.

而载脂蛋白E 4 等位基因 (ApoE-4) 与一般人群的认知和大脑衰退有关，其对 1 型糖尿病 (T1DM) 大脑的影响尚不清楚。因此，目的是确定 ApoE-4 和 T1DM 对作为最容易受到 ApoE 影响的大脑区域的认知表现和海马结构和连通性的影响4 对成年 T1DM 患者的影响。

对 104 名 T1DM 患者和 49 名对照受试者进行了血液采样，用于 ApoE 基因分型、神经心理学和神经影像学，以确定海马体积和静息状态连接。T1DM 状态与 ApoE-之间的相互作用4 存在被调查和调整年龄和平均收缩压。

无法对三名 T1DM 患者进行 ApoE 基因分型。在整体认知功能以及信息处理速度和注意力的子域中发现了显着的交互作用，表明两组之间 ApoE-4 的不同作用。此外，右侧海马与右侧后扣带回和缘上回的连接也存在相互作用。随后的组分析显示，T1DM 患者 ApoE-4 在这些具有增强连接性的认知领域表现更差，相对于没有 ApoE 的同行4. 相比之下，在患有 ApoE-的对照受试者中没有观察到认知影响，但连接性降低4. 在 T1DM 患者中，较高的右侧海马与后扣带回的连接与较差的整体认知功能有关。

结果可能表明 ApoE-4 的存在使我们的 T1DM 患者在年轻时更容易出现认知减退，可能是通过血管通路，需要进一步的纵向研究。