Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses
Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses
复制标题
DOI：
10.1136/bmjopen-2016-013187
复制
发表时间：
2017-01-01
期刊：
影响因子：
2.9
通讯作者：
O'Brien, John T.
中科院分区：
文献类型：
--
作者：
Bevan-Jones, W. Richard;Surendranathan, Ajenthan;O'Brien, John T.
前言：中枢神经系统炎症越来越多地被认为在痴呆和抑郁症等认知障碍中起作用，但尚不清楚这种炎症与神经病理学的其他方面、大脑结构和功能变化以及症状(通过临床和神经心理评估和核磁共振评估)之间的关系。这项研究将使用正电子发射断层扫描(PET)来探索这些病理生理学机制，它可以在体内成像炎症、淀粉样蛋白和沉积，结合神经心理特征、MRI和外周生物标记物分析。方法和分析使用配体[C-11]PK11195的PET成像，我们将测试与健康对照组相比，阿尔茨海默病、路易体痴呆、额颞叶痴呆、进行性核上性瘫痪、迟发性抑郁症和轻度认知障碍患者体内神经炎症的增加。我们将评估炎症改变区域是否与淀粉样蛋白和沉积有关(分别使用C-11标记的匹兹堡化合物B([C-11]PIB)和F-18标记的AV-1451进行评估)，以及MRI上发现的结构和连接标记。炎性生物标志物分析和外周血单核细胞免疫表型分析将确定中心性炎症和外周性炎症之间的相关性。最后，我们将检查在PET成像上看到的中枢炎性标志物是否与全球和特定领域的认知障碍有关，或者是否可以预测12个月后的认知下降。伦理和传播研究该研究方案获得了英格兰东部的当地伦理委员会和剑桥中央研究伦理委员会的批准(参考文献：13/EE/0104)。这项研究也得到了放射性物质管理咨询委员会(ARSAC)的批准，作为这一过程的一部分。数据将通过在国内和国际会议上的陈述以及主要在临床神经科学、神经学和精神病学期刊上发表的出版物来传播。
Introduction 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 deposition, together with neuropsychological profiling, MRI and peripheral biomarker analysis.Methods and analysis Using PET imaging of the ligand [C-11]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 deposition (assessed using C-11-labelled Pittsburgh Compound B ([C-11]PiB) and F-18-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 12months.Ethics and dissemination The study protocol was approved by the local ethics committee, East of EnglandCambridge 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.