White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers.
White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers.
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DOI：
10.3389/fnagi.2017.00179
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发表时间：
2017
影响因子：
4.8
通讯作者：
Gonzalez-Pinto A
中科院分区：
文献类型：
--
作者：
Besga A;Chyzhyk D;Gonzalez-Ortega I;Echeveste J;Graña-Lecuona M;Graña M;Gonzalez-Pinto A
背景：晚发性双相情感障碍(LOBD)是双相情感障碍(BD)在50岁以上的发展。它通常很难与阿尔茨海默病(AD)等其他老年性痴呆区分开来，因为它们都有认知和行为障碍的症状。目的：在AD和LOBD的比较中，我们寻找有显著差异的WM束体素簇，以及它与全身血浆生物标记物(炎症、神经营养因子和氧化应激)的相关性。材料：来自阿拉瓦大学医院的健康对照组(HC)(n=19)、AD患者(n=35)和LOBD患者(n=24)。在招募时采集血浆样本，并进行分析以提取炎症、氧化应激和神经营养因子。方法：从弥散加权成像(DWI)获得分数各向异性(FA)系数。基于区域的空间统计(TBSS)发现WM区域体素的FA骨架簇显示了HC、AD和LOBD之间所有可能的对比的显著差异。对所有对比度进行方差F检验。F检验的结果被用来掩蔽用于AD&>LOBD和LOBD&>AD对比的TBSS检测的簇，以选择用于相关性分析的图像簇。最后，计算了聚集区FA值与系统血浆生物标志物之间的皮尔逊相关系数。结果：与单因素方差F检验相比，TBSS在钳小束、下纵束、额枕下束和扣带回有明显的聚集性。相关分析发现AD与神经生长因子(NGF)和脑源性神经营养因子(BDNF)血液标志物呈显著负相关。AD与炎症标志物IL6呈负相关，LOBD与IL6呈正相关。结论：体素簇束图谱定位与LOBD患者比AD患者更严重的行为障碍和情绪障碍相一致。相关分析证实神经营养因子(NGF、BDNF)在AD发病中起重要作用，而LOBD病理生理学中缺乏神经营养因子。此外，IL1和IL6的相关性结果表明LOBD的炎症效应比AD更强。
Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectives: We look for WM tract voxel clusters showing significant differences when comparing of AD vs. LOBD, and its correlations with systemic blood plasma biomarkers (inflammatory, neurotrophic factors, and oxidative stress). Materials: A sample of healthy controls (HC) (n = 19), AD patients (n = 35), and LOBD patients (n = 24) was recruited at the Alava University Hospital. Blood plasma samples were obtained at recruitment time and analyzed to extract the inflammatory, oxidative stress, and neurotrophic factors. Several modalities of MRI were acquired for each subject, Methods: Fractional anisotropy (FA) coefficients are obtained from diffusion weighted imaging (DWI). Tract based spatial statistics (TBSS) finds FA skeleton clusters of WM tract voxels showing significant differences for all possible contrasts between HC, AD, and LOBD. An ANOVA F-test over all contrasts is carried out. Results of F-test are used to mask TBSS detected clusters for the AD > LOBD and LOBD > AD contrast to select the image clusters used for correlation analysis. Finally, Pearson's correlation coefficients between FA values at cluster sites and systemic blood plasma biomarker values are computed. Results: The TBSS contrasts with by ANOVA F-test has identified strongly significant clusters in the forceps minor, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum gyrus. The correlation analysis of these tract clusters found strong negative correlation of AD with the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) blood biomarkers. Negative correlation of AD and positive correlation of LOBD with inflammation biomarker IL6 was also found. Conclusion: TBSS voxel clusters tract atlas localizations are consistent with greater behavioral impairment and mood disorders in LOBD than in AD. Correlation analysis confirms that neurotrophic factors (i.e., NGF, BDNF) play a great role in AD while are absent in LOBD pathophysiology. Also, correlation results of IL1 and IL6 suggest stronger inflammatory effects in LOBD than in AD.