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. 2024 Dec;39(12):2280-2285.
doi: 10.1002/mds.30003. Epub 2024 Aug 30.

Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies

Tamara Shiner  1   2   3   4 , Gitit Kavé  5 , Anat Mirelman  2   3   6 , Keren Regev  7 , Yoav Piura  1 , Orly Goldstein  8 , Mali Gana Weisz  8 , Anat Bar-Shira  9 , Tanya Gurevich  2   3   4 , Avi Orr-Urtreger  2   3   8 , Roy N Alcalay  2   3   4   8   10 , Nir Giladi  2   3   4 , Noa Bregman  1   2   3
Affiliations

Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies

Tamara Shiner et al. Mov Disord. 2024 Dec.

Abstract

Background: Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear.

Objective: To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status.

Methods: One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed.

Results: GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly.

Conclusion: Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials.

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Figures

FIG. 1
FIG. 1
Cox proportional hazard regression for survival in months from diagnosis in GBA1 mutation carriers and non‐carriers adjusted for sex and age at onset. [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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