Gray and white matter damage are associated with motor symptoms in Parkinson’s disease

Abstract

AbstractBackgroundPrevious studies have found associations between atrophy in Substantia Nigra (SN) and White Matter Hyperintensities (WMH) of vascular origin and motor deficits in Parkinson’s disease (PD) patients (Zeighami et al. 2015, Pozorski et al. 2019). Here we assess the relationship between WMHs and SN atrophy and motor symptoms in PD.MethodData included 50 PD patients and 45 age‐matched controls with T1‐weighted and FLAIR scans at baseline, month18, and month36. WMHs were segmented using T1‐weighted and FLAIR images and a random forests classifier (Dadar et al. 2017, Figure 1.a). Deformation‐based morphometry was used to measure atrophy in Substantia Nigra (SN) (Figure 1.b, Ashburner et al 1998). The relationship between MRI features and clinical scores was assessed using mixed‐effects models: where Cohort denotes a categorical variable contrasting PD versus controls, and ID denotes the categorical random effects. The variables of interest were MRI‐Feature (implying an overall association between the MRI feature and clinical score of interest) and the interaction term Cohort:MRI‐Score (implying an additional PD‐specific impact of the MRI‐Feature on the Clinical‐Score). Log‐transformed WMH volumes and mean DBM score in left and right SN were used as MRI features. The motor subscore of Unified Parkinson's Disease Rating Scale (UPDRSIII) was used as the dependent variable of interest, reflecting motor deficits.ResultWMH load significantly increased with age in both groups (t=9.95, p<0.0001). We did not find a significant group difference in WMH volumes. However, WMH load was significantly associated with UPDRSIII in PDs (t=2.63, p=0.008), but not in controls (t=0.02, p=0.86), with a marginal interaction (t=1.67, p=0.05, Figure 2). DBM in both left and right SN significantly decreased with age (tLeftSN=‐5.79, tRightSN=‐6.33, p<0.0001), and were significantly different between the cohorts (Figure 3, tLeftSN=‐4.19, tRightSN=‐3.95, p<0.00001). UPDRSIII significantly increased with age (t=4.75, p<0.00001) and decrease in SN DBM (tLeftSN=‐2.02, tRightSN=‐1.88, p<0.05), with a significantly greater impact in PDs (Figure 4, tLeftSN=‐2.10, tRightSN=‐1.73, p<0.04).ConclusionIn our sample, both SN atrophy and WMH burden were significantly associated with additional motor deficits in PD, implying an additive contribution of both gray and white matter damage to the motor deficits in PD.