Zhang Wen, Lu Jiaming, Qing Zhao, Zhang Xin, Zhao Hui, Bi Yan, Zhang Bing
Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Department of Neurology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Front Aging Neurosci. 2022 Jan 31;14:781938. doi: 10.3389/fnagi.2022.781938. eCollection 2022.
Subcortical atrophy and increased cerebral β-amyloid and tau deposition are linked to cognitive decline in type 2 diabetes. However, whether and how subcortical atrophy is related to Alzheimer's pathology in diabetes remains unclear. This study therefore aimed to investigate subcortical structural alterations induced by diabetes and the relationship between subcortical alteration, Alzheimer's pathology and cognition.
Participants were 150 patients with type 2 diabetes and 598 propensity score-matched controls without diabetes from the Alzheimer's Disease Neuroimaging Initiative. All subjects underwent cognitive assessments, magnetic resonance imaging (MRI), and apolipoprotein E (ApoE) genotyping, with a subset that underwent amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) assays to determine cerebral β-amyloid deposition ( = 337) and CSF p-tau ( = 433). Subcortical structures were clustered into five modules based on Pearson's correlation coefficients of volumes across all subjects: the ventricular system, the corpus callosum, the limbic system, the diencephalon, and the striatum. Using structural equation modeling (SEM), we investigated the relationships among type 2 diabetes, subcortical structural alterations, and AD pathology.
Compared with the controls, the diabetic patients had significant reductions in the diencephalon and limbic system volumes; moreover, patients with longer disease duration (>6 years) had more severe volume deficit in the diencephalon. SEM suggested that type 2 diabetes, age, and the ApoE ε4 allele (ApoE-ε4) can affect cognition reduced subcortical structure volumes (total effect: age > ApoE-ε4 > type 2 diabetes). Among them, age and ApoE-ε4 strongly contributed to AD pathology, while type 2 diabetes neither directly nor indirectly affected AD biomarkers.
Our study suggested the subcortical atrophy mediated the association of type 2 diabetes and cognitive decline. Although both type 2 diabetes and AD are correlated with subcortical neurodegeneration, type 2 diabetes have no direct or indirect effect on the cerebral amyloid deposition and CSF p-tau.
皮质下萎缩以及脑内β-淀粉样蛋白和tau蛋白沉积增加与2型糖尿病患者的认知功能下降有关。然而，在糖尿病中皮质下萎缩与阿尔茨海默病病理改变之间是否存在关联以及如何关联仍不清楚。因此，本研究旨在探讨糖尿病引起的皮质下结构改变以及皮质下改变、阿尔茨海默病病理改变与认知功能之间的关系。
研究对象为来自阿尔茨海默病神经影像倡议项目的150例2型糖尿病患者和598例倾向得分匹配的非糖尿病对照者。所有受试者均接受认知评估、磁共振成像（MRI）和载脂蛋白E（ApoE）基因分型，部分受试者还接受了淀粉样蛋白正电子发射断层扫描（PET）和脑脊液（CSF）检测，以确定脑内β-淀粉样蛋白沉积（n = 337）和脑脊液p-tau水平（n = 433）。基于所有受试者各脑区体积的Pearson相关系数，将皮质下结构分为五个模块：脑室系统、胼胝体、边缘系统、间脑和纹状体。使用结构方程模型（SEM），我们研究了2型糖尿病、皮质下结构改变与阿尔茨海默病病理改变之间的关系。
与对照组相比，糖尿病患者的间脑和边缘系统体积显著减小；此外，病程较长（>6年）的患者间脑体积缩小更明显。结构方程模型表明，2型糖尿病、年龄和ApoE ε4等位基因（ApoE-ε4）可影响认知功能，通过减小皮质下结构体积起作用（总效应：年龄>ApoE-ε4>2型糖尿病）。其中，年龄和ApoE-ε4对阿尔茨海默病病理改变有强烈影响，而2型糖尿病对阿尔茨海默病生物标志物既无直接影响也无间接影响。
我们的研究表明皮质下萎缩介导了2型糖尿病与认知功能下降之间的关联。虽然2型糖尿病和阿尔茨海默病都与皮质下神经退行性变相关，但2型糖尿病对脑内淀粉样蛋白沉积和脑脊液p-tau水平无直接或间接影响。
