The aim of this study was to assess the longitudinal disease course of Parkinson’s disease (PD) patients with glucocerebrosidase (GBA) gene mutation (GBA-positive) compared to GBA-negative patients along a 5-year follow-up, evaluating changes in cortical thickness and clinical outcomes.

GBA mutations are the greatest genetic cause of PD, but a deep understanding on the longitudinal patterns of cortical atrophy in GBA-positive patients and the underlying neurodegenerative process is still lacking.

10 GBA-positive PD and 20 GBA-negative PD matched for age, sex, disease duration and severity underwent clinical, neuropsychological and MRI assessments at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared in terms of cortical thinning to a group of 22 age-matched healthy controls (HC), who underwent one MRI at study entry. Clinical, cognitive and cortical features were compared between patient groups at baseline and over time. 

At baseline, GBA-positive and GBA-negative patients had similar clinical and cognitive profiles. Compared to GBA-negative and HC, GBA-positive patients showed cortical thinning of the left temporal, parietal and occipital gyri. Over time, compared to GBA-negative PD, GBA-positive worsened significantly in motor symptoms and showed a greater pattern of bilateral cortical thinning involving also frontal cortices. After 60 months, compared to HC, GBA-negative PD showed a pattern of cortical thinning similar to that showed by GBA-positive at baseline.

Compared to GBA-negative, GBA-positive PD patients showed a greater and earlier cortical thinning which worsened over time. GBA-negative PD patients reached the pattern of cortical thinning of GBA-positive at the baseline only after 5 years, reflecting a slower disease progression.