Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive Parkinson’s disease patients

• DOI: 10.1007/s00415-021-10713-4
• Publication Date: 2021-07-23T06:02:48Z
• Authors: Michela Leocadi; Elisa Canu; Giulia Donzuso; Tanja Stojkovic; Silvia Basaia; Nikola Kresojević; Iva Stankovic; Elisabetta Sarasso; Noemi Piramide; Aleksandra Tomic; Vladana Markovic; Igor Petrovic; Elka Stefanova; Vladimir S. Kostic; Massimo Filippi; Federica Agosta
• Keywords: Parkinson Disease; Cortical thickness; 3. Good health; 03 medical and health sciences; Magnetic resonance imaging; Cognition; 0302 clinical medicine; Glucocerebrosidase gene; Mutation; Parkinson’s disease; Glucosylceramidase; Humans; GBA; Cognitive Dysfunction; Gray Matter

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.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.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.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.