壹生资讯-无症状成人血压相关白质微结构的不完整性与相关认知功能障碍

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无症状成人血压相关白质微结构的不完整性与相关认知功能障碍

2023-04-01作者：论坛报沐雨资讯

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Stroke & Vascular Neurology（SVN）最新上线文章“Blood pressure-related white matter microstructural disintegrity and associated cognitive function impairment in asymptomatic adults”，来自耶鲁大学医学院放射学和生物医学影像学系Seyedmehdi Payabvash等。

本研究旨在探讨与较高收缩压（systolic blood pressure, SBP）相关的白质（white matter, WM）微结构/细胞结构的不完整性模式，以及该模式是否介导了收缩压对中年人认知功能的影响。

研究团队基于英国生物样本库（UK Biobank）对40～69岁的社区志愿者开展研究，纳入了既往无卒中、痴呆、脱髓鞘疾病或创伤性脑损伤病史的参与者，分析了收缩压与磁共振扩散各参数的关联，包括部分各向异性指数（fractional anisotropy, FA）、平均弥散率（mean diffusivity, MD）、细胞内体积分数（intracellular volume fraction, ICVF；神经突密度量度）、各向同性（游离）水体积分数（isotropic（free）water volume fraction, ISOVF）和白质纤维束的方向弥散。基于以上研究结果，进一步探究WM扩散参数是否介导了收缩压对认知功能的影响。

研究团队分析了31363名平均年龄为63.8岁（标准差7.7）的参与者，其中包括女性16523名（53%）。研究发现，较高水平的收缩压与多个区域的白质不完整性指标和DTI参数相关 —— 即较低水平的FA和ICVF，较高水平的MD和ISOVF、定向弥散（orientation dispersion, OD）水平的高低取决于区域的不同。值得注意的是，相对于OD，与收缩压相关的FA、MD、ICVF和ISOVF变化的区域范围更为弥散。收缩压增加10 mmHg，与FA减少0.5%～1.5%以及MD增加0.5～2.2%相关。在不同的WM束中，内囊前肢、外囊、上方和后方放射冠始终显示出与较高水平收缩压相关的大多数DTI参数的显著变化，即其扩散参数受较高水平的收缩压影响最大（Figure 1-3）。

Figure 1. Statistical significance from association analyses results between systolic blood pressure and diffusion metrics across white matter (WM) tracts. (A) Fractional anisotropy, (B) Mean diffusivity, (C) Orientation Dispersion Index, (D) Isotropic (free) water volume fraction, and (E) Intracellular volume fraction - a measure of neurite density. The colour bars represent −log 10 p values from multivariable regression models. Only WM tracts reaching significance after Bonferroni correction are coloured.

Figure 2.Statistical significance from association analyses results between systolic blood pressure (SBP) and diffusion metrics across white matter tracts. The colour bars represent p values from multivariable regression models. Only p values reaching significance after Bonferroni correction are coloured. (B) Average percentage change in DTI metrics for each 10 mm Hg increase in SBP across white matter tracts. The colour bars represent the percentage change. Only values reaching significance after Bonferroni correction are coloured.

Figure 3. Statistical significance from association analyses results between systolic blood pressure (SBP) and diffusion metrics across white matter tracts. The colour bars represent p values from multivariable regression models. Only p values reaching significance after Bonferroni correction are coloured. (B) Average percentage change in DTI metrics for each 10 mm Hg increase in SBP across white matter tracts. The colour bars represent the percentage change. Only values reaching significance after Bonferroni correction are coloured.

研究结果表明，WM弥散参数介导了收缩压与认知功能的关系。经过邦弗朗尼校正（Bonferroni correction）后，在7组不同的认知功能参数中，仅“流体智力”与收缩压具有显著相关性。为进一步探究收缩压对流体智力的影响是否由WM完整性的变化介导，研究团队进行了中介分析。结果显示，收缩压对流体智力的影响确实是由多个WM束上的几个DTI参数的变化介导的。具体而言，即外囊和内囊前肢的微结构不完整性，以及小脑上脚和终纹，介导了收缩压对流体智力的影响。值得注意的是，外囊、内囊前肢和小脑上脚的平均FA分别介导了收缩压对流体智力影响的13%、9%和13%，外囊、内囊前、后肢和上放射冠的平均MD分别介导了收缩压对流体智力影响的5%、7%、7%和6%。校正教育水平后结果保持不变（Figure 4-5）。

Figure 4. Statistical significance from mediation analyses results depicting DTI metrics which significantly mediated the effects of systolic blood pressure on fluid intelligence across white matter (WM) tracts. (A) Fractional anisotropy, (B) mean diffusivity, (C) Orientation Dispersion Index, (D) Isotropic (free) water volume fraction and (E) Intracellular volume fraction - a measure of neurite density. The colour bars represent -log 10 p values from mediation analyses. Only WM tracts reaching significance after Bonferroni correction are coloured.

Figure 5. (A) Mediation analyses results with diffusion metrics highlighted which significantly mediated the effects of systolic blood pressure (SBP) on fluid intelligence across white matter (WM) tracts. Colour bars represent p values from mediation analyses. Only p values reaching significance after Bonferroni correction are highlighted. (B) Average mediated effects proportion of SBP thorough WM tract diffusion metrics on fluid intelligence. Colour bars represent the average mediated effects proportion. Only average mediated effects associated with p values reaching significance after Bonferroni correction are highlighted.

研究团队认为，在无症状成人中，较高水平的收缩压与广泛的脑白质微结构不完整性相关，部分原因是神经元数量减少，这或许介导了收缩压对流体智力的不良影响。部分白质纤维束弥散参数最能反映收缩压相关的脑实质损伤和认知障碍，或可作为评估降压试验治疗反应的影像学生物标志物。

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