Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Neuromuscular Research Center, Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Neuromuscular Research Center, Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Neurology Department, University Hospitals of Leicester NHS Trust, Leicester, UK.
Brain Res Bull. 2024 Dec;219:111125. doi: 10.1016/j.brainresbull.2024.111125. Epub 2024 Nov 13.
To characterize the longitudinal metabolite profile of the left dorsolateral prefrontal cortex (DLPFC) in amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS) and to examine its correlation with cognitive assessments.
Thirteen patients at baseline and ten at follow-up, along with 14 age-, sex-, and handedness-matched healthy controls (HCs), were recruited. Three Tesla with a 64-channel coil, Point-RESolved Spectroscopy (PRESS) sequence (TR=1500 ms and TE=140 ms) was used. Metabolites in the left DLPFC were quantified using LCModel. Cognitive performance and functional impairment were assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and Revised ALS Functional Rating Scale (ALSFRS-R), respectively. Group comparisons were adjusted for multiple comparisons (p < 0.05, Bonferroni correction). The links between the brain metabolites and cognitive function were investigated using relevant correlation tests (Pearson's or Spearman's).
Our analysis revealed a significant difference in the choline-to-creatine ratio (tCho/tCr) among the three groups. Baseline ALS patients showed a higher tCho/tCr ratio than HCs (p = 0.033, Bonferroni-corrected). Interestingly, the total N-acetyl aspartate (tNAA)/tCr ratio, a marker of neuronal health, was strongly positively correlated with visuospatial cognitive scores at baseline and follow-up. Furthermore, at follow-up, tNAA/tCr was positively correlated with the total scores and specific sub-scores on the ECAS, encompassing both ALS-specific and non-specific cognitive domains. At follow-up, positive correlations emerged between tNAA/tCr and the total language and executive function scores.
Metabolite alterations and correlations with cognition were observed in the left DLPFC of ALS patients, supporting extra-motor involvement and its association with cognitive decline.
使用磁共振波谱（MRS）描绘肌萎缩侧索硬化症（ALS）患者左侧背外侧前额叶皮质（DLPFC）的纵向代谢谱，并研究其与认知评估的相关性。
本研究共招募了 13 名基线期和 10 名随访期患者以及 14 名年龄、性别和惯用手匹配的健康对照者（HCs）。使用 3T 扫描仪和 64 通道线圈，采用点分辨波谱（PRESS）序列（TR=1500ms，TE=140ms）。使用 LCModel 定量分析左侧 DLPFC 的代谢物。使用爱丁堡认知和行为 ALS 筛查（ECAS）和修订版 ALS 功能评定量表（ALSFRS-R）分别评估认知表现和功能障碍。使用相关的相关性检验（Pearson 或 Spearman），对脑代谢物与认知功能之间的关系进行了研究。
我们的分析表明，三组之间胆碱/肌酸比（tCho/tCr）存在显著差异。基线期 ALS 患者的 tCho/tCr 比值高于 HCs（p=0.033，Bonferroni 校正）。有趣的是，总 N-乙酰天冬氨酸（tNAA）/tCr 比值，神经元健康的标志物，与基线和随访时的视觉空间认知评分呈强烈正相关。此外，在随访时，tNAA/tCr 与 ECAS 的总评分和特定子评分呈正相关，涵盖了 ALS 特异性和非特异性认知领域。在随访时，tNAA/tCr 与语言和执行功能总分呈正相关。
在 ALS 患者的左侧 DLPFC 中观察到代谢物改变和与认知的相关性，支持运动外的参与及其与认知下降的关联。
