Magnetic susceptibility source separation for assessing motor and cognitive functions in Parkinson disease

Background: Iron and myelin alterations contribute to the progression of Parkinson disease (PD). This study aimed to evaluate the associations of iron-related positive susceptibility and myelin-related negative susceptibility with motor and cognitive functions, and assess their utility in classifying PD with normal cognition (PD-CN) and with mild cognitive impairment (PD-MCI). Methods: We retrospectively reviewed 59 patients with PD-MCI and 58 with PD-CN. Magnetic susceptibility values were extracted using magnetic susceptibility source separation. Correlations of motor and cognitive functions with susceptibility values were evaluated, and classification models were developed to distinguish PD-MCI from PD-CN. Results: Positive susceptibility correlated with Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III off-state scores in the right internal globus pallidus and substantia nigra (r = 0.750 [95 % CI: 0.659 to 0.830], 0.758 [95 % CI: 0.681 to 0.822]) and Montreal Cognitive Assessment scores in the right caudate nucleus (r = −0.644 [95 % CI: −0.742 to −0.521]). Negative susceptibility correlated with MDS-UPDRS part III off-state scores in the bilateral external globus pallidus (right: r = 0.299 [95 % CI: 0.091 to 0.453], left: r = 0.285 [95 % CI: 0.112 to 0.444]). The positive susceptibility model achieved a sensitivity of 0.780 (95 % CI: 0.776 to 0.782), specificity of 0.793 (95 % CI: 0.790 to 0.796), and an ROC AUC of 0.856 (95 % CI: 0.855 to 0.859). Conclusions: Positive and negative susceptibility values were associated with motor and cognitive function in PD and proved effective in differentiating PD-MCI from PD-CN.