Impact of White Matter Hyperintensities Spatial Location on Cognition in Parkinson’s Disease

This study aims to examine how the spatial distribution of White Matter Hyperintensities (WMHs) in the brain is associated with cognition in individuals with Parkinson’s disease (PD). WMHs, which appear as bright areas on Fluid-Attenuated Inversion Recovery (FLAIR) MRI scans, are considered markers of vascular brain damage related to small vessel disease (Fazekas et al., 1993; Pantoni de Groot et al., 1998). Another approach is to separately examine WMHs across the different lobes of the brain to assess their specific cognitive correlates. Despite these varied methodologies, no clear consensus has emerged regarding the distinct cognitive consequences associated with the regional distribution of WMHs (Bolandzadeh et al., 2012; Brugulat-Serrat et al., 2020; Lu et al., 2024; Sanderson-Cimino et al., 2021; Soriano-Raya et al., 2012). The significance of WMHs spatial distribution has been previously explored in dementia such as Lewy Body dementia (Ghebremedhin et al., 2010), vascular dementia (Brown et al., 2007), Alzheimer’s disease (AD) (Yoshita et al., 2006) and even frontotemporal dementia (Caroppo et al., 2014). A meta-analysis of 36 studies found that spatial patterns of WMHs provided more detailed insights into cognitive impairment than total WMH volume burden alone in participants with these types of dementia (Hu et al., 2021). Specifically, PWMHs have been found to have stronger associations with cognitive deficits and increased rsk of dementia than DWMHs (Hu et al., 2021). DWMHs are more commonly linked to vascular dementia, whereas individuals with AD (Smith et al., 2016) tend to exhibit greater PWMH burden, and greater WMH volume in the parieto-occipital regions (Gootjes et al., 2004; Pålhaugen et al., 2021). Although, findings have been inconsistent (see Garnier et al., 2022, for a comprehensive review). In contrast, in PD much less is known about whether the spatial distribution of WMHs differs from that of the normal aging population, from other neurodegenerative conditions like AD, and whether inter-individual differences in spatial patterns of WMHs contribute to the heterogeneity in the cognitive deficits of PD. For instance, studies have reported that PWMHs are associated with greater impairment in executive function in PD (Kandiah et al., 2014). Conversely, other research suggests that DWMHs, rather than PWMHs, are more strongly correlated with cognitive deterioration in PD (Li, 2017). Using a lobar approach to quantify WMH distribution, one study found that frontal lobe WMH burden differed significantly between PD patients with MCI (PD-MCI) and those with normal cognition (PD-NC) (Jing et al., 2020), while other studies have found no such difference between PD-NC and PD-MCI patients (Wang et al., 2013). A recent meta-analysis by Zhao et al. (2023) highlights the inconsistencies across these findings. Overall, the effect of regional WMH on cognition in PD has yet to be clearly defined. This analysis, by combining both PWMHs vs. DWMHs segmentation and a lobar segmentation approach, aims to provide a more granular understanding of how regional WMHs contribute to cognitive deficits in PD.