Department of Psychiatry, University of Cambridge, Cambridge, UK.
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
BMJ Open. 2017 Jan 7;7(1):e013187. doi: 10.1136/bmjopen-2016-013187.
Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such inflammation relates to other aspects of neuropathology, structural and functional changes in the brain and symptoms (as assessed via clinical and neuropsychological assessment and MRI). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows in vivo imaging of inflammation, amyloid and τ deposition, together with neuropsychological profiling, MRI and peripheral biomarker analysis.
Using PET imaging of the ligand [C]PK11195, we will test for increased neuroinflammation in vivo in patients with Alzheimer's disease, Lewy body dementia, frontotemporal dementia, progressive supranuclear palsy, late-onset depression and mild cognitive impairment, when compared to healthy controls. We will assess whether areas of inflammatory change are associated with amyloid and τ deposition (assessed using C-labelled Pittsburgh Compound B ([C]PiB) and F-labelled AV-1451, respectively), as well as structural and connectivity markers found on MRI. Inflammatory biomarker analysis and immune-phenotyping of peripheral blood monocytes will determine the correlation between central inflammation and peripheral inflammation. Finally, we will examine whether central inflammatory markers seen on PET imaging are associated with global and domain specific cognitive impairments or predict cognitive decline over 12 months.
The study protocol was approved by the local ethics committee, East of England-Cambridge Central Research Ethics Committee (reference: 13/EE/0104). The study is also Administration of Radioactive Substances Advisory Committee (ARSAC) approved as part of this process. Data will be disseminated by presentation at national and international conferences and by publication, predominantly in journals of clinical neuroscience, neurology and psychiatry.
中枢神经系统炎症越来越被认为与痴呆和抑郁症等认知障碍有关，但尚不清楚这种炎症与大脑的其他病理学、结构和功能变化以及症状（通过临床和神经心理学评估以及 MRI 评估）有何关联。本研究将使用正电子发射断层扫描（PET）来探索这些病理生理机制，该技术允许对炎症、淀粉样蛋白和 τ 沉积进行体内成像，同时进行神经心理学分析、MRI 和外周生物标志物分析。
我们将使用配体 [C]PK11195 的 PET 成像，来检测阿尔茨海默病、路易体痴呆、额颞叶痴呆、进行性核上性麻痹、迟发性抑郁症和轻度认知障碍患者的体内神经炎症是否增加，并与健康对照组进行比较。我们将评估炎症变化区域是否与淀粉样蛋白和 τ 沉积（分别使用 C 标记的匹兹堡化合物 B [C]PiB 和 F 标记的 AV-1451 评估）以及 MRI 上发现的结构和连接标记物相关。炎症生物标志物分析和外周血单核细胞免疫表型将确定中枢炎症与外周炎症之间的相关性。最后，我们将检查 PET 成像上观察到的中枢炎症标志物是否与整体和特定领域的认知障碍相关，或者是否可以预测 12 个月内的认知下降。
该研究方案已获得当地伦理委员会——东英格兰剑桥中央研究伦理委员会（参考编号：13/EE/0104）的批准。该研究还作为这一过程的一部分获得了放射性物质管理咨询委员会（ARSAC）的批准。数据将通过在国家和国际会议上的演讲以及发表在临床神经科学、神经病学和精神病学杂志等期刊上进行传播。
