Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive Parkinson's disease patients.
OBJECTIVE
To study the longitudinal disease course of Parkinson's disease (PD) patients with glucocerebrosidase (GBA) mutation (GBA-positive) compared to PD non-carriers (GBA-negative) along a 5-year follow-up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and gray-matter (GM) volumes.


METHODS
Ten GBA-positive and 20 GBA-negative PD patients underwent clinical, neuropsychological, and MRI assessments (cortical thickness and subcortical, hippocampal, and amygdala volumes) at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared with 22 age-matched healthy controls. Clinical, cognitive, and MRI features were compared between groups at baseline and over time.


RESULTS
At baseline, GBA-positive and GBA-negative PD patients had similar clinical and cognitive profiles. Compared to GBA-negative and controls, GBA-positive patients showed cortical thinning of left temporal, parietal, and occipital gyri. Over time, compared to GBA-negative, GBA-positive PD patients progressed significantly in motor and cognitive symptoms, and showed a greater pattern of cortical thinning of posterior regions, and frontal and orbito-frontal cortices. After 5 years, compared to controls, GBA-negative PD patients showed a pattern of cortical thinning similar to that showed by GBA-positive cases at baseline. The two groups of patients showed similar patterns of subcortical, hippocampal, and amygdala volume loss over time.


CONCLUSIONS
Compared to GBA-negative PD, GBA-positive patients experienced a more rapid motor and cognitive decline together with a greater, earlier and faster cortical thinning. Cortical thickness measures may be a useful tool for monitoring and predicting PD progression in accordance with the genetic background.
['Leocadi|Michela|M|', 'Canu|Elisa|E|', 'Donzuso|Giulia|G|', 'Stojkovic|Tanja|T|', 'Basaia|Silvia|S|', 'Kresojević|Nikola|N|', 'Stankovic|Iva|I|', 'Sarasso|Elisabetta|E|', 'Piramide|Noemi|N|', 'Tomic|Aleksandra|A|', 'Markovic|Vladana|V|', 'Petrovic|Igor|I|', 'Stefanova|Elka|E|', 'Kostic|Vladimir S|VS|', 'Filippi|Massimo|M|', 'Agosta|Federica|F|http://orcid.org/0000-0003-3121-4979']
GBA Cortical thickness Glucocerebrosidase gene Magnetic resonance imaging Parkinson’s disease