Category: Parkinson's Disease: Genetics
Objective: Survival assessment of PD patients genetically tested at Tel-Aviv Sourasky Medical Center between 2005-2025. We hypothesize that LRRK2-PD would show higher survival rates compared with GBA1-PD and that EOPD will shorter life expectancy compared with published norms.
Background: Patients living with PD face increased mortality and disability compared to the general population. Mutations in the glucocerebrosidase 1 (GBA1) and leucine-rich repeat kinase 2 (LRRK2) genes are associated with Parkinson’s disease (PD) phenotype. The contribution of genetic status to long-term survival, has not been studied thoroughly.
Method: 2039 PD patients recruited between 2005-2025 at Tel-Aviv Medical Center were genotyped for mutations in the GBA1 and LRRK2 genes. National death registries were studied to identify date of death. The primary endpoint was defined as overall survival. Regression analysis was performed to assess the risk for each group. Separate analysis comparing EOPD (age of onset <50) to late-onset PD (LOPD) was also conducted.
Results: Mortality hazard ratios (HR) were significantly increased for GBA1-PD; 1.52 (95% CI: 1.27-1.81) and reduced for LRRK2-PD; 0.75 (95% CI: 0.59-0.94) compared to idiopathic PD (iPD). Mean survival for all groups ranged from 15-20 years from onset, significantly lower than expected survival durations. Females were associated with lower mortality HR=0.69 (95% CI: 0.61-0.79). EOPD patients had increased overall survival compared to LOPD, with significantly lower age at death (67.8±9.2 vs. 80.2±7.3), consistent across genetic subgroups.
Conclusion: PD is associated with reduced longevity compared to population norms. LRRK2-PD has reduced mortality and GBA1-PD has increased mortality compared with iPD. EOPD is associated with longer disease duration and lower overall life expectancy compared to patients with LOPD. These findings can assist physicians in discussing prognosis with patients and caregivers and demonstrate the need for research directed at these unique patient sub-groups to identify factors and interventions to help personalize patient care.
Survival of PD patients by genetic subgroup
Survival of GBA1 patients: Mild, Severe, Variant
Survival of early and late onset PD, age at death
Survival of PD patients by genotype and onset age
Observed and expected mortality rates
To cite this abstract in AMA style:
R. Rubin, RN. Alcalay, N. Omer, O. Goldstein, M. Gana Weisz, A. Mirelman, A. Thaler. The Effect of LRRK2 and GBA1 Mutations on Survival in Early- and Late-onset Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/the-effect-of-lrrk2-and-gba1-mutations-on-survival-in-early-and-late-onset-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-lrrk2-and-gba1-mutations-on-survival-in-early-and-late-onset-parkinsons-disease/