Gu Xiaochun, Zhao Moyan, Han Xiao, Liu Li
Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Department of Histology Embryology, Medical School, Southeast University, 87#Dingjiaqiao Road, Nanjing 210009, China; Key Laboratory of Developmental Genes and Human Diseases, Department of Histology Embryology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China; State Key Laboratory of Space Medicine Fundamentals and Application, Chinese Astronaut Research and Training Center, During Review Process, China.
Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Department of Histology Embryology, Medical School, Southeast University, 87#Dingjiaqiao Road, Nanjing 210009, China.
Clin Neurol Neurosurg. 2020 Apr;191:105679. doi: 10.1016/j.clineuro.2020.105679. Epub 2020 Jan 24.
Observational studies suggested an association of the Presenilin-1 (PSEN1) genotype with neuroimaging markers within Alzheimer's disease. However, whether the PSEN1 genotype and neuroimaging markers is a harbinger of Alzheimer's disease remains controversial. We aimed to examine the association of the PSEN1 mutation with neuroimaging markers in Alzheimer's disease: hippocampal volume, cerebral metabolism and brain amyloid deposition. We performed a systematic review and meta-analysis of 13 studies identified in Pubmed and Medline from 1997 to 2019 (n = 164). The pooled standard mean difference (SMD) was used to evaluate the association between the PSEN1 mutation and hippocampal volume and cerebral metabolism rate for glucose (CMRgl). A meta-analysis was also performed regarding the amyloid deposition between the PSEN1+ and PSEN1- groups. In order to accurately study whether PSEN1 independently was associated with changes in related image markers, sub-meta analyses was performed. The PSEN1 mutation was associated with a smaller hippocampal volume (pooled SMD: -3.3; 95 % CI: -5.36 to -1.24; p = 0.002) and decreased cerebral metabolism (pooled SMD: -1.73; 95 % CI: -2.7 to -0.76; p < 0.0001). Additionally, PSEN1 was associated with increased cerebral amyloid deposition as detected by a positron emission tomography tracer (pooled SMD: 4.58; 95 % CI: 1.37-7.8; p = 0.0005). PSEN1 was associated with a decreased hippocampal volume in MRI markers, cerebral glucose hypometabolism, and increased cerebral amyloid deposition. These associations may indicate the potential role of neuroimaging markers for the diagnosis of Alzheimer's disease.
观察性研究表明早老素-1（PSEN1）基因型与阿尔茨海默病的神经影像学标志物之间存在关联。然而，PSEN1基因型和神经影像学标志物是否为阿尔茨海默病的先兆仍存在争议。我们旨在研究PSEN1突变与阿尔茨海默病神经影像学标志物之间的关联：海马体积、脑代谢和脑淀粉样蛋白沉积。我们对1997年至2019年在Pubmed和Medline中检索到的13项研究（n = 164）进行了系统评价和荟萃分析。采用合并标准平均差（SMD）来评估PSEN1突变与海马体积及葡萄糖脑代谢率（CMRgl）之间的关联。还对PSEN1+组和PSEN1-组之间的淀粉样蛋白沉积进行了荟萃分析。为了准确研究PSEN1是否独立与相关影像标志物的变化有关，进行了亚组荟萃分析。PSEN1突变与较小的海马体积（合并SMD：-3.3；95%CI：-5.36至-1.24；p = 0.002）和脑代谢降低（合并SMD：-1.73；95%CI：-2.7至-0.76；p < 0.0001）相关。此外，正电子发射断层显像示踪剂检测显示PSEN1与脑淀粉样蛋白沉积增加有关（合并SMD：4.58；95%CI：1.37 - 7.8；p = 0.0005）。PSEN1与MRI标志物显示的海马体积减小、脑葡萄糖代谢减低及脑淀粉样蛋白沉积增加有关。这些关联可能表明神经影像学标志物在阿尔茨海默病诊断中的潜在作用。
