4.5 Article

Predicting severity and prognosis in Parkinson's disease from brain microstructure and connectivity

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NEUROIMAGE-CLINICAL
卷 25, 期 -, 页码 -

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ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2019.102111

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资金

  1. Canadian Institutes for Health Research [FDN-143242]
  2. Natural Sciences and Engineering Research Council of Canada
  3. Michael J. Fox Foundation
  4. Weston Brain Institute
  5. Alzheimer Association
  6. Montreal Neurological Institute
  7. AbbVie
  8. Avid
  9. Biogen
  10. Bristol-Myers Squibb
  11. Covance
  12. GE Healthcare
  13. Genentech
  14. GlaxoSmithKline
  15. Lilly
  16. Lundbeck
  17. Merck
  18. Meso Scale Discovery
  19. Pfizer
  20. Piramal
  21. Roche
  22. Sanofi Genzyme
  23. Servier
  24. Teva
  25. UCB

向作者/读者索取更多资源

Objectives: Investigating biomarkers to demonstrate progression of Parkinson's disease (PD) is of high priority. We investigated the association of brain structural properties with progression of clinical outcomes and their ability to differentiate clinical subtypes of PD. Methods: A comprehensive set of clinical features was evaluated at baseline and 4.5-year follow-up for 144 de-novo PD patients from the Parkinson's Progression Markers Initiative. We created a global composite outcome (GCO) by combining z-scores of non-motor and motor symptoms, motor signs, overall activities of daily living and global cognition, as a single numeric indicator of prognosis. We classified patients into three subtypes based on multi-domain clinical criteria: 'mild motor-predominant', 'intermediate' and 'diffuse-malignant'. We analyzed diffusion-weighted scans at the early drug-naive stage and extracted fractional anisotropy and mean diffusivity (MD) of basal ganglia and cortical sub-regions. Then, we employed graph theory to calculate network properties and used network-based statistic to investigate our primary hypothesis. Results: Baseline MD of globus pallidus was associated with worsening of motor severity, cognition, and GCO after 4.5 years of follow-up. Connectivity disruption at baseline was correlated with decline in cognition, and increase in GCO. Baseline MD of nucleus accumbens, globus pallidus and basal-ganglia were linked to clinical subtypes at 4.5-year of follow-up. Disruption in sub-cortical networks associated with being subtyped as 'diffuse-malignant' versus 'mild motor-predominant' after 4.5 years. Conclusions: Diffusion imaging analysis at the early de-novo stage of PD was able to differentiate clinical sub-types of PD after 4.5 years and was highly associated with future clinical outcomes of PD.

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