Distinctive cognitive phenotypes in Parkinson’s disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective study

Background: Cognitive impairment is a major non-motor complication of Parkinson’s disease (PD). GBA mutations are associated with an increased risk, with PD-GBA+ patients typically showing earlier disease onset and faster cognitive decline. However, the specific cognitive phenotype of these patients...

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Main Authors: Chiara Longo, Marco Liccari, Ruggero Bacchin, Costanza Papagno, Donatella Ottaviani, Raffaella Di Giacopo, Mauro Catalan, Alina Menichelli, Massimo Marano, Alessio Di Fonzo, Giovanni Duro, Carmela Zizzo, Paolo Manganotti, Bruno Giometto, Maria Chiara Malaguti
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Clinical Parkinsonism & Related Disorders
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590112525000696
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author Chiara Longo
Marco Liccari
Ruggero Bacchin
Costanza Papagno
Donatella Ottaviani
Raffaella Di Giacopo
Mauro Catalan
Alina Menichelli
Massimo Marano
Alessio Di Fonzo
Giovanni Duro
Carmela Zizzo
Paolo Manganotti
Bruno Giometto
Maria Chiara Malaguti
author_facet Chiara Longo
Marco Liccari
Ruggero Bacchin
Costanza Papagno
Donatella Ottaviani
Raffaella Di Giacopo
Mauro Catalan
Alina Menichelli
Massimo Marano
Alessio Di Fonzo
Giovanni Duro
Carmela Zizzo
Paolo Manganotti
Bruno Giometto
Maria Chiara Malaguti
author_sort Chiara Longo
collection DOAJ
description Background: Cognitive impairment is a major non-motor complication of Parkinson’s disease (PD). GBA mutations are associated with an increased risk, with PD-GBA+ patients typically showing earlier disease onset and faster cognitive decline. However, the specific cognitive phenotype of these patients remains unclear. Aim: To provide a detailed neuropsychological profile of PD-GBA+ patients compared to PD-GBA− patients. Methods: Data from 18 PD-GBA+ and 68 PD-GBA− patients were retrospectively analyzed. All participants underwent comprehensive neurological evaluations of motor and non-motor symptoms, along with a Level II neuropsychological assessment based on the MDS criteria for mild cognitive impairment (MCI). Patients with dementia were excluded. Results: PD-GBA+ patients showed significantly lower cognitive performance, particularly on the RAVLT immediate recall (RAVLT-IR, p < 0.001) and delayed recall (RAVLT-DR, p = 0.002). All PD-GBA+ patients exhibited an amnestic multi-domain MCI phenotype. In contrast, the PD-GBA− group predominantly showed a non-amnestic single-domain MCI, characterized by a dysexecutive profile. Additionally, PD-GBA+ patients had a higher prevalence of freezing of gait (p < 0.001), right-sided motor symptom lateralization (p = 0.011), and REM sleep behavior disorder (p = 0.006). Conclusions: PD-GBA+ patients exhibit a distinctive cognitive phenotype, already evident in the early stages of the disease. These results highlight the added value of Level II neuropsychological assessment in accurately characterizing the clinical phenotype and identifying patients at higher risk of developing dementia. Early cognitive profiling may thus contribute to more targeted monitoring and personalized therapeutic strategies.
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spelling doaj-art-93ca6b43239f4a7c9920d19fd0350bd72025-08-20T03:33:38ZengElsevierClinical Parkinsonism & Related Disorders2590-11252025-01-011310036510.1016/j.prdoa.2025.100365Distinctive cognitive phenotypes in Parkinson’s disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective studyChiara Longo0Marco Liccari1Ruggero Bacchin2Costanza Papagno3Donatella Ottaviani4Raffaella Di Giacopo5Mauro Catalan6Alina Menichelli7Massimo Marano8Alessio Di Fonzo9Giovanni Duro10Carmela Zizzo11Paolo Manganotti12Bruno Giometto13Maria Chiara Malaguti14Department of Neurology, Azienda Provinciale per i Servizi Sanitari (APSS), 38122 Trento, Italy; Department of Psychology, Azienda Provinciale per i Servizi Sanitari (APSS), 38122 Trento, Italy; Corresponding author at: Largo Medaglie d’Oro, 9, 38122 Trento, Italy.Clinical Unit of Neurology, Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), Trieste, Italy; Pineta del Carso, Viale Stazione, 26, 34011 Aurisina, ItalyDepartment of Neurology, Azienda Provinciale per i Servizi Sanitari (APSS), 38122 Trento, ItalyCenter for Mind/Brain Sciences (CIMeC), University of Trento, 38068 Rovereto, ItalyDepartment of Neurology, Azienda Provinciale per i Servizi Sanitari (APSS), 38122 Trento, ItalyDepartment of Neurology, Azienda Provinciale per i Servizi Sanitari (APSS), 38122 Trento, ItalyClinical Unit of Neurology, Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), Trieste, ItalyClinical Unit of Neurology, Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), Trieste, ItalyUnit of Neurology, Neurophysiology, Neurobiology and Psychiatry, Department of Medicine, University Campus Bio-Medico of Rome, Rome, Italy; Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyDino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, ItalyInstitute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyInstitute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, ItalyClinical Unit of Neurology, Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), Trieste, Italy; Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, ItalyDepartment of Neurology, Azienda Provinciale per i Servizi Sanitari (APSS), 38122 Trento, Italy; Center for Mind/Brain Sciences (CIMeC), University of Trento, 38068 Rovereto, ItalyDepartment of Neurology, Azienda Provinciale per i Servizi Sanitari (APSS), 38122 Trento, ItalyBackground: Cognitive impairment is a major non-motor complication of Parkinson’s disease (PD). GBA mutations are associated with an increased risk, with PD-GBA+ patients typically showing earlier disease onset and faster cognitive decline. However, the specific cognitive phenotype of these patients remains unclear. Aim: To provide a detailed neuropsychological profile of PD-GBA+ patients compared to PD-GBA− patients. Methods: Data from 18 PD-GBA+ and 68 PD-GBA− patients were retrospectively analyzed. All participants underwent comprehensive neurological evaluations of motor and non-motor symptoms, along with a Level II neuropsychological assessment based on the MDS criteria for mild cognitive impairment (MCI). Patients with dementia were excluded. Results: PD-GBA+ patients showed significantly lower cognitive performance, particularly on the RAVLT immediate recall (RAVLT-IR, p < 0.001) and delayed recall (RAVLT-DR, p = 0.002). All PD-GBA+ patients exhibited an amnestic multi-domain MCI phenotype. In contrast, the PD-GBA− group predominantly showed a non-amnestic single-domain MCI, characterized by a dysexecutive profile. Additionally, PD-GBA+ patients had a higher prevalence of freezing of gait (p < 0.001), right-sided motor symptom lateralization (p = 0.011), and REM sleep behavior disorder (p = 0.006). Conclusions: PD-GBA+ patients exhibit a distinctive cognitive phenotype, already evident in the early stages of the disease. These results highlight the added value of Level II neuropsychological assessment in accurately characterizing the clinical phenotype and identifying patients at higher risk of developing dementia. Early cognitive profiling may thus contribute to more targeted monitoring and personalized therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S2590112525000696Parkinson’s DiseaseGBA mutationCognitionMild Cognitive ImpairmentMemory
spellingShingle Chiara Longo
Marco Liccari
Ruggero Bacchin
Costanza Papagno
Donatella Ottaviani
Raffaella Di Giacopo
Mauro Catalan
Alina Menichelli
Massimo Marano
Alessio Di Fonzo
Giovanni Duro
Carmela Zizzo
Paolo Manganotti
Bruno Giometto
Maria Chiara Malaguti
Distinctive cognitive phenotypes in Parkinson’s disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective study
Clinical Parkinsonism & Related Disorders
Parkinson’s Disease
GBA mutation
Cognition
Mild Cognitive Impairment
Memory
title Distinctive cognitive phenotypes in Parkinson’s disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective study
title_full Distinctive cognitive phenotypes in Parkinson’s disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective study
title_fullStr Distinctive cognitive phenotypes in Parkinson’s disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective study
title_full_unstemmed Distinctive cognitive phenotypes in Parkinson’s disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective study
title_short Distinctive cognitive phenotypes in Parkinson’s disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective study
title_sort distinctive cognitive phenotypes in parkinson s disease patients with gba mutations and without dementia a multicentre cross sectional retrospective study
topic Parkinson’s Disease
GBA mutation
Cognition
Mild Cognitive Impairment
Memory
url http://www.sciencedirect.com/science/article/pii/S2590112525000696
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