White Matter Hyper Intensities and Cognitive Decline in Parkinson’s Disease

White Matter Hyperintensities (WMHs) have been associated with the Alzheimer’s disease. Cognitive decline is a common non-motormanifestations of Parkinson’s disease (PD) with an unclear pathogenesis. In this study, we systematically reviewed the association of WMH with dementia (PD-D) and mild cognitive impairment (PD-MCI) in PD patients. Materials and Methods: PubMed database was searched for the relevant studies using terms related to WMH, PD and cognitive disorders.Data extraction was performed using a pre-specified spreadsheet and Newcastle-Ottawa Scale was used for the quality assessment. Meta-analysis was performed to calculate the pooled odds ratio of PD-D and PD-MCI in patients with WMH. Additionally, the pooled WMHvolume in PD-D and PD-MCI patients was compared to cognitively normal PD (PD-CN) patients. Results: Twenty-one studies with 2961 patients comprising of 1548 PD-CN, 668 PD-MCI and 397 PD-D patients were included in this systematic review. Nine out of12 studies found a positive association between the total WMH and PD-D. The pooled OR of PD-D in patients with WMH was 2.8 (CI95: 1.93 - 3.99, p < 0.05). However, the pooled WMH volume in PD-D and PD-CN groups was not significantly different (Hedge’s g = 0.66, CI95: -0.13 – 1.46, p = 0.10). Eight out of 11 studies did not show a significant association between total WMH and PD-MCI. Pooled OR of MCI in PD patients with WMH was 2.2 (CI95: 1.62 - 3.04, p < 0.05) and there was a small significant difference in the pooled WMH volume between the PD-MCI and PD-CN groups (Hedge’s g = 0.34, CI95: 0.05-0.64, p < 0.05). Conclusion: Similar to AD, WMH seems to contribute to the development of cognitive impairment in PD patients. Further studies are needed to localize these WMHs in cognitively impaired PD patientsand to understand the pathogenesis of WMH in the cognitive decline.