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Research paper
Subcortical white matter hyperintensities within the cholinergic pathways of Parkinson's disease patients according to cognitive status
  1. Jaeseung Shin1,
  2. Sungeun Choi1,
  3. Ji E Lee1,
  4. Hye Sun Lee2,
  5. Young H Sohn1,
  6. Phil Hyu Lee1,3
  1. 1Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
  2. 2Department of Biostatistics, Yonsei University College of Medicine, Seoul, Korea
  3. 3Severance Biomedical Science Institute, Seoul, Korea
  1. Correspondence to Professor P H Lee, Department of Neurology, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, South Korea; phisland{at}


Background White matter hyperintensities (WMH) in the cholinergic pathways show a stronger correlation with cognitive performance than general WMH in Alzheimer's disease. However, the role of WMH within the cholinergic pathways in cognitive dysfunction has not been investigated in Parkinson's disease (PD).

Method The severity of WMH within the cholinergic pathways of PD subgroups with intact cognition (PD-IC, n=44), mild cognitive impairment (PD-MCI, n=87) and dementia (PDD, n=40) were compared using the Cholinergic Pathways Hyperintensities Scale (CHIPS), and the correlation between the CHIPS score and performance on individual tests of cognitive subdomains were analysed.

Results The mean CHIPS score was significantly higher in patients with PDD compared with those with PD-IC (p=0.03) or PD-MCI (p=0.015). The CHIPS score in patients with PD was negatively correlated with general cognition assessed using the Mini-Mental State Examination (r=−0.28, p<0.001) and positively with the Unified Parkinson's Disease Rating Scale motor score (r=0.24, p=0.002). The CHIPS score showed a significant correlation with cognitive performance on individual cognitive subdomains and had the highest independent correlations with contrasting programme (β=−0.33, p<0.001) and forward digit span (β=−0.17, p=0.04).

Conclusions This study demonstrated that the burden of WMH within cholinergic pathways was significantly higher in patients with PDD relative to other groups, and that cholinergic WMH was significantly correlated with a decline in frontal executive function and attention.

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  • JS and SC contributed equally to this work.

  • Funding This study was supported by a grant from the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A091159).

  • Competing interests None.

  • Ethics approval The study was approved by the institutional review board of Yonsei University Severance Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data Sharing statement The corresponding author declares that all authors have agreed to the conditions about data sharing.