Gilad Yahalom1, Lior Greenbaum2, Simon Israeli-Korn3, Tsvia Fay-Karmon3, Vered Livneh3, Jennifer A Ruskey4, Léanne Roncière5, Armaghan Alam6, Ziv Gan-Or7, Sharon Hassin-Baer8. 1. The Movement Disorders Institute, Department of Neurology and Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel. Electronic address: gyahalom@gmail.com. 2. Sackler Faculty of Medicine, Tel-Aviv University, Israel; The Danek Gertner Institute of Human Genetics and Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel. 3. The Movement Disorders Institute, Department of Neurology and Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel. 4. Montreal Neurological Institute, McGill University, Montréal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. 5. Faculty of Medicine, McGill University, Montréal, Quebec, Canada. 6. Montreal Neurological Institute, McGill University, Montréal, QC, Canada. 7. Montreal Neurological Institute, McGill University, Montréal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada. 8. The Movement Disorders Institute, Department of Neurology and Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Abstract
INTRODUCTION: The clinical characteristics of Parkinson's disease (PD) associated with both the LRRK2 p.G2019S mutation and a GBA variant (LRRK2-GBA-PD) have not yet been determined. METHODS: In this retrospective observational study of Ashkenazi-Jewish (AJ) PD patients, we describe the clinical course and characteristics of LRRK2-GBA-PD and estimate the risk to develop PD for the double mutation carriers. Odds ratios (OR) were estimated using published data on frequencies of GBA and LRRK2 mutations. Demographic and clinical data was retrieved from medical records and from rating at last visit. RESULTS: Our analysis included 236 PD patients, divided into four groups: LRRK2-PD (n = 66), GBA-PD (n = 78), GBA-LRRK2-PD (n = 12) and mutation-negative PD (MNPD, n = 80 randomly selected). The estimated ORs in different models for GBA-LRRK2 PD were 15-28 (95% CI 6.7-72.0, p < 0.0001), compared to AJ controls. Using logistic regression (while controlling for sex, age at onset and PD duration), we found that probable REM-sleep behavior disorder (RBD) was significantly more common for GBA-PD than for LRRK2-PD, while none of the GBA-LRRK2-PD patients reported RBD. Dementia was significantly more common for GBA-PD than for the LRRK2-PD and MNPD. Psychosis was the most common for GBA-PD and least common for LRRK2-GBA-PD. CONCLUSIONS: While GBA-PD is characterized by higher rates of dementia, probable RBD and psychosis, it seems that compared to the other groups, these features are less common for LRRK2-GBA-PD. This may imply to a possible protective effect of LRRK2 p.G2019S mutation among GBA variant carriers.
INTRODUCTION: The clinical characteristics of Parkinson's disease (PD) associated with both the LRRK2p.G2019S mutation and a GBA variant (LRRK2-GBA-PD) have not yet been determined. METHODS: In this retrospective observational study of Ashkenazi-Jewish (AJ) PD patients, we describe the clinical course and characteristics of LRRK2-GBA-PD and estimate the risk to develop PD for the double mutation carriers. Odds ratios (OR) were estimated using published data on frequencies of GBA and LRRK2 mutations. Demographic and clinical data was retrieved from medical records and from rating at last visit. RESULTS: Our analysis included 236 PD patients, divided into four groups: LRRK2-PD (n = 66), GBA-PD (n = 78), GBA-LRRK2-PD (n = 12) and mutation-negative PD (MNPD, n = 80 randomly selected). The estimated ORs in different models for GBA-LRRK2 PD were 15-28 (95% CI 6.7-72.0, p < 0.0001), compared to AJ controls. Using logistic regression (while controlling for sex, age at onset and PD duration), we found that probable REM-sleep behavior disorder (RBD) was significantly more common for GBA-PD than for LRRK2-PD, while none of the GBA-LRRK2-PD patients reported RBD. Dementia was significantly more common for GBA-PD than for the LRRK2-PD and MNPD. Psychosis was the most common for GBA-PD and least common for LRRK2-GBA-PD. CONCLUSIONS: While GBA-PD is characterized by higher rates of dementia, probable RBD and psychosis, it seems that compared to the other groups, these features are less common for LRRK2-GBA-PD. This may imply to a possible protective effect of LRRK2p.G2019S mutation among GBA variant carriers.
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