Cai, Mengfei, Jacob, Mina A, Marques, José, Norris, David G, Duering, Marco, Esselink, Rianne A J, Zhang, Yuhu, Leeuw, Frank-Erik de, and Tuladhar, Anil M
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 (β = −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. [ABSTRACT FROM AUTHOR]