White matter hyperintensities in patients with Parkinson's disease: A systematic review and meta-analysis

Introduction: Mechanisms driving neurodegeneration in Parkinson's disease (PD) are unclear and neurovascular dysfunction may be a contributing factor. White matter hyperintensities (WMH) are commonly found on brain MRI in patients with PD. It is controversial if they are more prevalent or more severe in PD compared with controls. This systematic review aims to answer this question. Methods: A systematic search of electronic databases was conducted for studies of WMH in patients with PD. A qualitative synthesis was done for studies reporting WMH prevalence or WMH scores on a visual rating scale (VRS). In studies reporting total WMH volume, the difference between patients with PD and controls was pooled using random effects meta-analysis. Results: Among 3860 subjects from 24 studies, 2360 were cases and 1500 controls. Fifteen studies reported WMH scores and four studies reported the prevalence of WMH. On VRS, five studies reported no difference in WMH scores, three found higher WMH scores in PD compared to controls, three reported increased WMH scores either in periventricular or deep white matter, and four reported higher scores only in PD with dementia. In studies reporting WMH volume, there was no difference between patients with PD and controls (pooled standardized mean difference = 0.1, 95%CI: - 0.1-0.4, I2 = 81%). Conclusion: WMH are not more prevalent or severe in patients with PD than in age-matched controls. PD dementia may have more severe WMH compared to controls and PD with normal cognition. Prospective studies using standardized methods of WMH assessment are needed.