Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, Cranmer Terrace, Tooting, London, SW17 ORE, UK.
Institute of Infection and Immunity, St George's University of London, Cranmer Terrace, Tooting, London, SW17 ORE, UK.
BMC Pulm Med. 2017 Jun 19;17(1):92. doi: 10.1186/s12890-017-0435-1.
Brain pathology is relatively unexplored in chronic obstructive pulmonary disease (COPD). This study is a comprehensive investigation of grey matter (GM) and white matter (WM) changes and how these relate to disease severity and cognitive function.
T1-weighted and fluid-attenuated inversion recovery images were acquired for 31 stable COPD patients (FEV 52.1% pred., PaO 10.1 kPa) and 24 age, gender-matched controls. T1-weighted images were segmented into GM, WM and cerebrospinal fluid (CSF) tissue classes using a semi-automated procedure optimised for use with this cohort. This procedure allows, cohort-specific anatomical features to be captured, white matter lesions (WMLs) to be identified and includes a tissue repair step to correct for misclassification caused by WMLs. Tissue volumes and cortical thickness were calculated from the resulting segmentations. Additionally, a fully-automated pipeline was used to calculate localised cortical surface and gyrification. WM and GM tissue volumes, the tissue volume ratio (indicator of atrophy), average cortical thickness, and the number, size, and volume of white matter lesions (WMLs) were analysed across the whole-brain and regionally - for each anatomical lobe and the deep-GM. The hippocampus was investigated as a region-of-interest. Localised (voxel-wise and vertex-wise) variations in cortical gyrification, GM density and cortical thickness, were also investigated. Statistical models controlling for age and gender were used to test for between-group differences and within-group correlations. Robust statistical approaches ensured the family-wise error rate was controlled in regional and local analyses.
There were no significant differences in global, regional, or local measures of GM between patients and controls, however, patients had an increased volume (p = 0.02) and size (p = 0.04) of WMLs. In patients, greater normalised hippocampal volume positively correlated with exacerbation frequency (p = 0.04), and greater WML volume was associated with worse episodic memory (p = 0.05). A negative relationship between WML and FEV % pred. approached significance (p = 0.06).
There was no evidence of cerebral atrophy within this cohort of stable COPD patients, with moderate airflow obstruction. However, there were indications of WM damage consistent with an ischaemic pathology. It cannot be concluded whether this represents a specific COPD, or smoking-related, effect.
慢性阻塞性肺疾病（COPD）患者的大脑病理学研究相对较少。本研究全面调查了灰质（GM）和白质（WM）的变化，以及这些变化与疾病严重程度和认知功能的关系。
对 31 名稳定期 COPD 患者（FEV 52.1%pred.，PaO 10.1 kPa）和 24 名年龄、性别匹配的对照者进行 T1 加权和液体衰减反转恢复图像采集。使用针对本队列优化的半自动程序对 T1 加权图像进行 GM、WM 和脑脊液（CSF）组织分类。该程序允许捕获特定于队列的解剖特征、识别白质病变（WML），并包括组织修复步骤，以纠正由 WML 引起的分类错误。从所得分割中计算组织体积和皮质厚度。此外，还使用全自动流水线计算局部皮质表面和脑回。分析全脑和局部（每个解剖叶和深部 GM）的 WM 和 GM 组织体积、组织体积比（萎缩指标）、平均皮质厚度以及白质病变（WML）的数量、大小和体积。作为感兴趣区域研究了海马体。还研究了皮质脑回、GM 密度和皮质厚度的局部（体素和顶点）变化。使用控制年龄和性别的统计模型来测试组间差异和组内相关性。稳健的统计方法确保在区域和局部分析中控制了错误发现率。
患者与对照组之间的 GM 全球、区域或局部指标均无显著差异，但患者的 WML 体积（p = 0.02）和大小（p = 0.04）增加。在患者中，正常化海马体体积与加重频率呈正相关（p = 0.04），WML 体积与情景记忆呈负相关（p = 0.05）。WML 与 FEV % pred. 之间的负相关关系接近显著（p = 0.06）。
在这个稳定期 COPD 患者队列中，尽管存在中度气流阻塞，但没有脑萎缩的证据。然而，有 WM 损伤的迹象，与缺血性病变一致。尚不能确定这是否代表特定的 COPD 或与吸烟有关的影响。
