Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
J Neurol Neurosurg Psychiatry. 2018 Feb;89(2):185-196. doi: 10.1136/jnnp-2017-316633. Epub 2017 Sep 9.
Over the past years, positron emission tomography (PET) imaging studies have investigated striatal molecular changes in premanifest and manifest Huntington's disease (HD) gene expansion carriers (HDGECs), but they have yielded inconsistent results.
To systematically examine the evidence of striatal molecular alterations in manifest and premanifest HDGECs as measured by PET imaging studies.
MEDLINE, ISI Web of Science, Cochrane Library and Scopus databases were searched for articles published until 7 June 2017 that included PET studies in manifest and premanifest HDGECs. Meta-analyses were conducted with random effect models, and heterogeneity was addressed with I index, controlling for publication bias and quality of study. The primary outcome was the standardised mean difference (SMD) of PET uptakes in the whole striatum, caudate and putamen in manifest and premanifest HDGECs compared with healthy controls (HCs).
Twenty-four out of 63 PET studies in premanifest (n=158) and manifest (n=191) HDGECs and HCs (n=333) were included in the meta-analysis. Premanifest and manifest HDGECs showed significant decreases in dopamine D receptors in caudate (SMD=-1.233, 95% CI -1.753 to -0.713, p<0.0001; SMD=-5.792, 95% CI -7.695 to -3.890, p<0.0001) and putamen (SMD=-1.479, 95% CI -1.965 to -0.992, p<0.0001; SMD=-5.053, 95% CI -6.558 to -3.549, p<0.0001), in glucose metabolism in caudate (SMD=-0.758, 95% CI -1.139 to -0.376, p<0.0001; SMD=-3.738, 95% CI -4.880 to -2.597, p<0.0001) and putamen (SMD=-2.462, 95% CI -4.208 to -0.717, p=0.006; SMD=-1.650, 95% CI -2.842 to -0.458, p<0.001) and in striatal PDE10A binding (SMD=-1.663, 95% CI -2.603 to -0.723, p=0.001; SMD=-2.445, 95% CI -3.371 to -1.519, p<0.001).
PET imaging has the potential to detect striatal molecular changes even at the early premanifest stage of HD, which are relevant to the neuropathological mechanisms underlying the development of the disease.
在过去的几年中，正电子发射断层扫描（PET）成像研究已经研究了前显型和显型亨廷顿病（HD）基因扩展携带者（HDGEC）中的纹状体分子变化，但结果不一致。
系统检查通过 PET 成像研究在显型和前显型 HDGEC 中测量的纹状体分子改变的证据。
在 2017 年 6 月 7 日之前，在 MEDLINE、ISI Web of Science、Cochrane Library 和 Scopus 数据库中搜索了包括在显型和前显型 HDGEC 中进行的 PET 研究的文章。使用随机效应模型进行荟萃分析，并使用 I 指数解决异质性，控制发表偏倚和研究质量。主要结果是在显型和前显型 HDGEC 与健康对照组（HC）相比，整个纹状体、尾状核和壳核中的 PET 摄取的标准化均数差（SMD）。
在包括 158 名前显型和 191 名显型 HDGEC 以及 333 名 HC 的 63 项 PET 研究中，有 24 项研究被纳入荟萃分析。前显型和显型 HDGEC 的尾状核和壳核中的多巴胺 D 受体明显减少（SMD=-1.233，95%CI-1.753 至-0.713，p<0.0001；SMD=-5.792，95%CI-7.695 至-3.890，p<0.0001）和壳核（SMD=-1.479，95%CI-1.965 至-0.992，p<0.0001；SMD=-5.053，95%CI-6.558 至-3.549，p<0.0001），尾状核和壳核的葡萄糖代谢明显减少（SMD=-0.758，95%CI-1.139 至-0.376，p<0.0001；SMD=-3.738，95%CI-4.880 至-2.597，p<0.0001）和壳核（SMD=-2.462，95%CI-4.208 至-0.717，p=0.006；SMD=-1.650，95%CI-2.842 至-0.458，p<0.001）和纹状体 PDE10A 结合（SMD=-1.663，95%CI-2.603 至-0.723，p=0.001；SMD=-2.445，95%CI-3.371 至-1.519，p<0.001）。
即使在 HD 的早期前显型阶段，PET 成像也具有检测纹状体分子变化的潜力，这与疾病发展的神经病理学机制有关。
