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

Abstract

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.

Cognitive and Motor Correlates of Grey and White Matter Pathology in Parkinson’s Disease

“…Although surprising, this is in agreement with previous studies showing a positive impact of hyperlipidimia on lowering WMH burden in three independent large samples, suggesting a relatively protective role of hyperlipidimia on small-vessel disease 42,43 . Unlike previous studies, we did not find an association between hypertension and WMH burden 16,42 (Table 2). This might be due to the relatively smaller sample size or that the blood presure levels were well-controlled in both controls and PD patients in our sample (Table 1).…”

“…WMH volume increased with age in both controls and PD patients (Figure 2.e). Similar to the majority of previous studies which report no disease-specific differences in WMH loads in PD patients and agematched normal controls, we did not find a significant difference in WMH burden between controls and PD patients 16,18,38,39 . However, increase in WMH burden was associated with greater cognitive decline and motor and gait deficits, as previously reported in the literature 7,8,[16][17][18][19][20][21] (Figures 3.a, 5.a, and 6.a, respectively).…”

“…Given that some of the symptoms associated with WMHs in non-PD individuals overlap with PD features, one might hypothesize that coexistence of WMHs in PD patients would lead to even greater cognitive and motor deficits. However, WMH associations with cognitive and motor symptoms are less well established and consistent in PD, although some recent studies report such relationships in both de novo 16 and later stage PD patients 7,8,[17][18][19][20][21] .…”

BISON: Brain tISue segmentatiON pipeline using T1-weighted magnetic resonance images and a random forests classifier

“…This is particularly important in neurodegenerative disease populations (e.g. Alzheimer's disease and Parkinson's disease), where WMHs are very common findings (van der Flier et al, 2018) and have been shown to interact with neurodegeneration and contribute to cognitive deficits (Dadar et al, 2018c(Dadar et al, , 2019 and therefore their misclassification as GM may systematically bias the findings of such studies.…”

An MRI Atrophy Biomarker Predicts Global Prognosis in Early De Novo Parkinson’s Disease

“…27 Our previous work with this PD network atrophy measure is supportive of a propagating process. 7,28,29,30 Moreover, the discovery that neurotoxic misfolded α-synuclein can propagate trans-neuronally provides a mechanism for the propagation hypothesis first proposed by Braak et al . 31 This suggests that the pattern of disease could be stereotyped in its spatial distribution as determined by the brains' normal wiring diagram (or connectome) 7 .…”