White matter hyperintensities are linked to future cognitive decline in de novo Parkinson's disease patients.

White Matter Hyperintensities (WMHs) are associated with cognitive decline in aging and Alzheimer's disease. However, the pathogenesis of cognitive decline in Parkinson's disease (PD) is not as clearly related to vascular causes, and therefore the role of WMHs as a marker of small-vessel disease (SVD) in PD is less clear. Currently, SVD in PD is assessed and treated independently of the disease. However, if WMH as the major MRI sign of SVD has a higher impact on cognitive decline in PD patients than in healthy controls, vascular pathology needs to be assessed and treated with a higher priority in this population. Here we investigate whether the presence of WMHs leads to increased cognitive decline in de novo PD, and if these effects relate to cortical atrophy. WMHs and cortical thickness were measured in de novo PD patients and age-matched controls (NPD  = 365, NControl  = 174) from Parkinson's Progression Markers Initiative (PPMI) to study the relationship between baseline WMHs, future cognitive decline (follow-up: 4.09 ± 1.14 years) and cortical atrophy (follow-up: 1.05 ± 0.10 years). PD subjects with high baseline WMH loads had significantly greater cognitive decline than i) PD subjects with low WMH load, and ii) control subjects with high WMH load. Furthermore, in PD subjects, high WMH load resulted in more cortical thinning in the right frontal lobe. Theses results show that the presence of WMHs in de novo PD patients predicts greater future cognitive decline and cortical atrophy than in normal aging.