Objective: In this study, we investigate the relationship between white matter hyperintensities (WMH) and Parkinson’s disease (PD) cognitive impairment using a comprehensive neuropsychological battery with Level-II criteria for domain-specific subtyping.

Background: PD patients are at an elevated risk of developing cognitive impairment. The cognitive domains affected include executive function, attention, memory, visuospatial abilities, and language. Lewy-body pathology, Alzheimer’s disease-type pathology, vascular pathology, and mixed pathology have all been implicated on postmortem tissue analysis. However, etiology matters and the relative contribution of WMH due to vascular disease is still unclear [1].

Methods: A total of 79 PD participants (67.2 ± 8.8 years) were included in the present study, 65 with no or punctuate WMH and 14 with early-confluent or confluent WMH (Fazekas’ Scale). Level-II assessment of cognitive function [2] included tests of executive (SDMT, FAS), attention/working memory (TMT-A/-B, WMS III-DS, Stroop), episodic memory (CVLT-II, BVMT-R), visuospatial (HVOT, JLO-V) and language function (BNT, DKEF, Semantic Fluency Test). Cognitive impairment was defined as >1.5 SD below age and education-matched normative values on at least two tests; cognitively impaired participants were then subtyped according to which domains included the impaired tests.

Results: The two WMH groups did not differ in education, duration of PD diagnosis and MDS-UPDRS motor score (part-III). Binary logistic regression analysis showed WMH severity significantly predicted impairment in executive function (Exp(B)=6.35, 95% CI=1.73-23.34, p=0.005), attention/working memory (Exp(B)=4.67, 95% CI=1.34-16.26, p=0.016) and episodic memory (Exp(B)=4.69, 95% CI=1.18-18.67, p=0.028), and trended towards prediction of visuospatial function. WMH severity did not predict impairment in language function.

Conclusions: This study demonstrates an interaction effect of WMH and domain-specific cognitive dysfunction in PD. Using comprehensive neuropsychological testing and level-II subtyping criteria, we found higher WMH burden in PD is associated with worse executive function, attention/working memory and episodic memory. Early treatment of vascular risk factors could modulate cognitive impairments in a subgroup of PD patients, but further investigations are needed.

Presented: NINDS Udall Centers Directors’ Meeting (11/2016)

References: [1] Litvan, I., et al. Diagnostic Criteria for Mild Cognitive Impairment in Parkinson’s Disease: Movement Disorder Society Task Force Guidelines. Movement Disorders: 27(3), 2012.

[2] Veselý, B. & Rektor, I. The contribution of white matter lesions (WML) to Parkinson’s disease cognitive impairment symptoms: A critical review of the literature. Parkinsonism and Related Disorders: 22, 2016.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/domain-specific-impact-of-cerebral-white-matter-hyperintensities-on-parkinsons-disease-cognitive-functioning/