It is increasingly apparent that even subclinical liver fibrosis is associated with cognitive impairment and frailty. However, it’s impact on motor and cognitive performance in Parkinson’s Disease (PD) is not well understood.

We conducted a retrospective cohort study using the Parkinson’s Progression Marker Initiative (PPMI), a longitudinal study collecting data on PD patients. Our exposure was liver fibrosis at baseline, based on the validated Fibrosis-4 (FIB4) score calculated using age, platelet count, aspartate and alanine aminotransferase values. We dichotomized participants as high (≥1.3) versus low (<1.3) FIB4. Our outcomes were the Montreal Cognitive Assessment (MoCA) and Unified Parkinson’s Disease Rating Scale part III (UPDRSIII) on- and off-treatment scores. We used linear mixed models to assess the relationships between FIB4 at baseline and MoCA and UPDRSIII scores, both at baseline and over time during the eight years of available follow-up data. Models were adjusted for demographics, comorbidities, and alcohol use.

In adjusted models, UPDRSIII on-treatment and off-treatment scores were not significantly different at baseline or over time when comparing participants with high versus low FIB4. High FIB4 score was not associated with low MoCA scores at baseline. However, MoCA scores in the high FIB4 group declined more over time, with an average difference in rate of change of 0.13 (95% CI, 0.06-0.20). This relationship was maintained after adjusting for potential confounders, with a difference in rate of change of 0.12 (95% CI, 0.05-0.20).

In PD, a high liver fibrosis score was not associated with motor progression but was associated with faster cognitive decline. Liver health may therefore be an under-appreciated determinant of cognitive outcomes in PD.