Aims

Glucocerebrosidase gene (GBA) mutations are the greatest genetic cause of Parkinson’s disease (PD). We studied the longitudinal disease course of GBA-positive compared to GBA-negative patients along a 5-year follow-up, evaluating changes in cortical thickness and clinical outcomes.

Methods

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 the study entry. Clinical, cognitive and cortical features were compared between patient groups at baseline and over time.

Results

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.

Conclusions

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.

Supported by: Ministry of Education and Science Republic of Serbia (Grant #175090).