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<p>Parkinson’s disease (PD) is a progressive neurodegenerative disorder featured impaired bioenergetics and mitochondrial dysfunction. Creatine (Cr) supplementation has been suggested as a pathophysiology-targeted treatment strategy; however, clinical outcomes remain inconsistent despite encouraging preclinical findings. The lack of methods to measure Cr distribution in the human brain may hinder the investigation. This study utilized a novel neuroimaging technique, guanidino chemical exchange saturation transfer (GuanCEST) MRI, to assess regional Cr levels in patients with PD (PwPD) and healthy controls (HCs). Twenty-five patients with PD and 24 age- and sex-matched HCs were enrolled. GuanCEST values in the caudate nucleus were significantly lower in PwPD (1.67 ± 0.26%) than HCs (1.82 ± 0.16%), <i>p</i> = 0.023. Moreover, GuanCEST signal reductions correlated with increasing PD severity, particularly in thalamic subregions. Kendall’s correlation revealed a significant negative correlation between GuanCEST values in the internal medullary lamina and MDS-UPDRS-III scores (<i>r</i> = −0.44, <i>p</i> = 0.03). Regional ANCOVA further indicated that GuanCEST values in this region decreased by approximately 0.01% per unit increase in MDS-UPDRS-III (<i>p</i> = 0.007), adjusted for age and sex. These findings highlight GuanCEST MRI’s potential as a noninvasive biomarker of Cr metabolism in PD, offering insights into disease mechanisms, therapeutic optimization, and clinical trial designs.</p>

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Creatine-weighted imaging in patients with Parkinson’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月13日

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  • Kexin Wang,
  • Nirbhay Narayan Yadav,
  • Zijiang Yang,
  • Ted M. Dawson,
  • Peter van Zijl,
  • Kelly A. Mills,
  • Jiadi Xu,
  • Jannik Prasuhn

摘要

Parkinson’s disease (PD) is a progressive neurodegenerative disorder featured impaired bioenergetics and mitochondrial dysfunction. Creatine (Cr) supplementation has been suggested as a pathophysiology-targeted treatment strategy; however, clinical outcomes remain inconsistent despite encouraging preclinical findings. The lack of methods to measure Cr distribution in the human brain may hinder the investigation. This study utilized a novel neuroimaging technique, guanidino chemical exchange saturation transfer (GuanCEST) MRI, to assess regional Cr levels in patients with PD (PwPD) and healthy controls (HCs). Twenty-five patients with PD and 24 age- and sex-matched HCs were enrolled. GuanCEST values in the caudate nucleus were significantly lower in PwPD (1.67 ± 0.26%) than HCs (1.82 ± 0.16%), p = 0.023. Moreover, GuanCEST signal reductions correlated with increasing PD severity, particularly in thalamic subregions. Kendall’s correlation revealed a significant negative correlation between GuanCEST values in the internal medullary lamina and MDS-UPDRS-III scores (r = −0.44, p = 0.03). Regional ANCOVA further indicated that GuanCEST values in this region decreased by approximately 0.01% per unit increase in MDS-UPDRS-III (p = 0.007), adjusted for age and sex. These findings highlight GuanCEST MRI’s potential as a noninvasive biomarker of Cr metabolism in PD, offering insights into disease mechanisms, therapeutic optimization, and clinical trial designs.