Longitudinal clinical, cognitive and neuroanatomical changes over five years in GBA‐positive Parkinson’s disease patients

Abstract Background Glucocerebrosidase gene (GBA) mutations are the greatest genetic cause of Parkinson’s disease (PD). The aim of this study was to monitor the longitudinal disease course of PD patients with GBA mutation (GBA‐positive) at diagnosis compared to PD noncarriers (GBA‐negative) along a 5‐year follow‐up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and subcortical volumes. Method 10 GBA‐positive and 20 GBA‐negative PD at diagnosis underwent clinical, neuropsychological and brain 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 thickness and subcortical volumes to a group of 22 age‐matched healthy controls (HC). Clinical, cognitive and cortical/subcortical MRI features were compared between groups at baseline and over time. Result 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 left temporal, parietal and occipital gyri. Over time, compared to GBA‐negative, GBA‐positive worsened significantly in motor and cognitive symptoms, and showed a greater pattern of bilateral cortical thinning involving also frontal cortices. After 60 months, compared to HC, GBA‐negative PD patients showed a pattern of cortical thinning similar to that shown by GBA‐positive at baseline. The two groups of patients showed similar patterns of subcortical volume loss over time. Conclusion Compared to GBA‐negative patients, GBA‐positive PD 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. This study highlights the importance of the early detection of GBA mutation in PD patients. Funding: This study was supported by the Ministry of Education and Science of the Republic of Serbia (Grant #175090).