Structural Network Efficiency Predicts Conversion to Incident Parkinsonism in Patients With Cerebral Small Vessel Disease

Mengfei Cai, Mina A. Jacob, José Marques, David G. Norris, Marco Duering, Rianne A.J. Esselink, Yuhu Zhang, Frank Erik De Leeuw, Anil M. Tuladhar*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: To investigate whether structural network disconnectivity is associated with parkinsonian signs and their progression, as well as with an increased risk of incident parkinsonism. Methods: In a prospective cohort (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study) consisting of 293 participants with small vessel disease (SVD), we assessed parkinsonian signs and incident parkinsonism over an 8-year follow-up. In addition, we reconstructed the white matter network followed by graph-theoretical analyses to compute the network metrics. Conventional magnetic resonance imaging markers for SVD were assessed. Results: We included 293 patients free of parkinsonism at baseline (2011), with a mean age 68.8 (standard deviation [SD] 8.4) years, and 130 (44.4%) were men. Nineteen participants (6.5%) developed parkinsonism during a median (SD) follow-up time of 8.3 years. Compared with participants without parkinsonism, those with all-cause parkinsonism had higher Unified Parkinson's Disease Rating scale (UPDRS) scores and lower global efficiency at baseline. Baseline global efficiency was associated with UPDRS motor scores in 2011 (β = -0.047, p < .001) and 2015 (ß = -0.84, p < .001), as well as with the changes in UPDRS scores during the 4-year follow-up (β = -0.63, p = .004). In addition, at the regional level, we identified an inter-hemispheric disconnected network associated with an increased UPDRS motor score. Besides, lower global efficiency was associated with an increased risk of all-cause and vascular parkinsonism independent of SVD markers. Conclusions: Our findings suggest that global network efficiency is associated with a gradual decline in motor performance, ultimately leading to incident parkinsonism in the elderly with SVD. Global network efficiency may have the added value to serve as a useful marker to capture changes in motor signs.

Original languageEnglish
Article numberglad182
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number1
Early online date1 Aug 2023
Publication statusPublished - 1 Jan 2024
Externally publishedYes


  • Motor disturbance
  • Network efficiency
  • Parkinsonism
  • Small vessel disease


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