Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea; Department of Neurology, Inje University Sanggye Paik Hospital, Seoul, South Korea.
Department of Biostatistics, Yonsei University College of Medicine, Seoul, South Korea.
Parkinsonism Relat Disord. 2022 Apr;97:1-7. doi: 10.1016/j.parkreldis.2022.02.020. Epub 2022 Mar 3.
This study investigated the relationship between white matter hyperintensities (WMHs), nigrostriatal dopamine deficits, and cognitive decline in patients with drug-naïve early-stage Parkinson's disease (PD).
This cross-sectional study enrolled 309 non-demented patients with de novo PD who underwent [F] N-(3-fluoropropyl)-2β-carbonethoxy-3β-(4-iodophenyl) nortropane positron emission tomography, brain magnetic resonance imaging, and a detailed neuropsychological test at baseline. We quantified dopamine transporter (DAT) availability in each striatal sub-region and applied the Scheltens scale to assess the severity of periventricular and deep WMHs. The relationships between WMHs, DAT availability, and cognition in PD were assessed using multivariate linear regression and mediation analyses while adjusting for age at parkinsonian symptom onset, sex, disease duration, and vascular risk factors.
The severities of periventricular and frontal WMHs were associated with striatal DAT availability. Periventricular WMHs affected the level of cognitive performance in all cognitive domains, while frontal WMHs affected the attention/working memory and frontal/executive function domains. The effects of WMHs on attention/working memory and frontal/executive dysfunction were mostly direct with minimal mediating effects through striatal DAT availability. Meanwhile, striatal DAT availability fully mediated the association between WMHs and cognitive impairment in the visuospatial and memory function domains.
This study demonstrated the different effects of WMHs on cognitive impairment depending on the cognitive domains in PD. These findings suggest a close link between comorbid WMHs, striatal dopamine depletion, and cognition in patients with PD.
本研究旨在探讨未经药物治疗的早期帕金森病（PD）患者的脑白质高信号（WMHs）、黑质纹状体多巴胺缺失与认知下降之间的关系。
本横断面研究纳入了 309 例新发 PD 且无痴呆的患者，他们在基线时接受了[F] N-（3-氟丙基）-2β-碳乙氧基-3β-（4-碘苯基）-nortropane 正电子发射断层扫描、脑磁共振成像和详细的神经心理学测试。我们量化了每个纹状体亚区的多巴胺转运体（DAT）的可用性，并应用 Scheltens 量表评估了脑室周围和深部 WMH 的严重程度。在调整了帕金森病症状出现年龄、性别、疾病持续时间和血管危险因素后，我们使用多元线性回归和中介分析评估了 PD 患者中 WMHs、DAT 可用性和认知之间的关系。
脑室周围和额部 WMHs 的严重程度与纹状体 DAT 可用性相关。脑室周围 WMHs 影响了所有认知领域的认知表现水平，而额部 WMHs 影响了注意力/工作记忆和额/执行功能领域。WMHs 对注意力/工作记忆和额/执行功能障碍的影响主要是直接的，通过纹状体 DAT 可用性的中介作用很小。同时，纹状体 DAT 可用性完全介导了 WMHs 与 PD 患者视空间和记忆功能领域认知障碍之间的关联。
本研究表明，WMHs 对 PD 患者认知障碍的影响因认知领域而异。这些发现表明，PD 患者的合并 WMHs、纹状体多巴胺耗竭与认知之间存在密切联系。
