Teng Zhenjie, Feng Jing, Liu Ronghui, Ji Yifan, Xu Jing, Jiang Xin, Chen Huifang, Dong Yanhong, Meng Nan, Xiao Yining, Xie Xiaohua, Lv Peiyuan
Department of Neurology, Hebei Medical University, Shijiazhuang, China.
Department of Neurology, Hebei General Hospital, Shijiazhuang, China.
Front Aging Neurosci. 2022 Jul 15;14:868777. doi: 10.3389/fnagi.2022.868777. eCollection 2022.
To investigate the relations of serum total homocysteine (tHcy) with cerebral small vessel disease (CSVD) and cognitive function and evaluate whether CSVD mediates the effect of serum tHcy on cognitive function.
A total of 1,033 consecutive eligible participants who received serum tHcy, brain magnetic resonance imaging (MRI), and neuropsychological assessment were included in this retrospective study. White matter hyperintensity, lacune, cerebral microbleed, and enlarged perivascular space were evaluated based on brain MRI. We used multivariate binary logistic regression analysis, multivariate ordinal logistic regression analysis, and mediation analyses to assess the relations of serum tHcy with CSVD and cognitive function.
Serum tHcy levels were higher in patients with cognitive impairment than those with no cognitive impairment. Logistic regression analyses showed elevated serum tHcy was associated with cognitive impairment [odds ratio (OR): 10.475; 95% confidence interval (CI): 4.522 to 24.264; < 0.001] and a higher CSVD burden score (OR: 17.151; 95% CI: 8.785 to 33.921; < 0.001) after adjusting potential confounders. Compared with the lowest tHcy quartile, the multivariable-adjusted OR of the highest quartile was 4.851 (95% CI: 3.152 to 7.466; for the trend < 0.001) for cognitive impairment, 3.862 (95% CI: 2.467 to 6.047; for the trend < 0.001) for a severe CSVD burden score. Mediation analyses showed significant moderating effects (9.3-23.6%) by different imaging markers of CSVD on the association between higher serum tHcy levels and cognitive impairment.
Elevated serum tHcy is associated with cognitive impairment and the development of CSVD. A proportion of the association between elevated serum tHcy and cognitive impairment may be attributed to the presence of different imaging markers of CSVD, especially the severe CSVD burden score.
探讨血清总同型半胱氨酸（tHcy）与脑小血管病（CSVD）及认知功能的关系，并评估CSVD是否介导血清tHcy对认知功能的影响。
本回顾性研究纳入了1033名连续入选的符合条件的参与者，他们接受了血清tHcy检测、脑磁共振成像（MRI）和神经心理学评估。基于脑MRI评估白质高信号、腔隙、脑微出血和血管周围间隙增宽情况。我们使用多变量二元逻辑回归分析、多变量有序逻辑回归分析和中介分析来评估血清tHcy与CSVD及认知功能的关系。
认知障碍患者的血清tHcy水平高于无认知障碍者。逻辑回归分析显示，在调整潜在混杂因素后，血清tHcy升高与认知障碍相关[比值比（OR）：10.475；95%置信区间（CI）：4.522至24.264；P<0.001]，且与更高的CSVD负担评分相关（OR：17.151；95%CI：8.785至33.921；P<0.001）。与最低tHcy四分位数相比，最高四分位数的多变量调整后OR在认知障碍方面为4.851（95%CI：3.152至7.466；趋势P<0.001），在严重CSVD负担评分方面为3.862（95%CI：2.467至6.047；趋势P<0.001）。中介分析显示，CSVD的不同影像学标志物对血清tHcy水平升高与认知障碍之间的关联具有显著的调节作用（9.3 - 23.6%）。
血清tHcy升高与认知障碍及CSVD的发生发展相关。血清tHcy升高与认知障碍之间的部分关联可能归因于CSVD不同影像学标志物的存在，尤其是严重CSVD负担评分。
