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

Tamara Shiner; Gitit Kavé; Anat Mirelman; Keren Regev; Yoav Piura; Orly Goldstein; Mali Gana Weisz; Anat Bar-Shira; Tanya Gurevich; Avi Orr-Urtreger; Roy N. Alcalay; Nir Giladi; Noa Bregman

doi:10.1002/mds.30003

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

Tamara Shiner^*, Gitit Kavé, Anat Mirelman, Keren Regev, Yoav Piura, Orly Goldstein, Mali Gana Weisz, Anat Bar-Shira, Tanya Gurevich, Avi Orr-Urtreger, Roy N. Alcalay, Nir Giladi, Noa Bregman

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Movement Disorders
DOIs	https://doi.org/10.1002/mds.30003
State	Accepted/In press - 2024

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Shiner, T., Kavé, G., Mirelman, A., Regev, K., Piura, Y., Goldstein, O., Gana Weisz, M., Bar-Shira, A., Gurevich, T., Orr-Urtreger, A., Alcalay, R. N., Giladi, N., & Bregman, N. (Accepted/In press). Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies. Movement Disorders. https://doi.org/10.1002/mds.30003

@article{bfc79164401a40a385c8371edb2ca2e6,

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

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.",

author = "Tamara Shiner and Gitit Kav{\'e} and Anat Mirelman and Keren Regev and Yoav Piura and Orly Goldstein and {Gana Weisz}, Mali and Anat Bar-Shira and Tanya Gurevich and Avi Orr-Urtreger and Alcalay, {Roy N.} and Nir Giladi and Noa Bregman",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2024",

doi = "10.1002/mds.30003",

language = "אנגלית",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley & Sons Inc.",

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TY - JOUR

T1 - Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies

AU - Shiner, Tamara

AU - Kavé, Gitit

AU - Mirelman, Anat

AU - Regev, Keren

AU - Piura, Yoav

AU - Goldstein, Orly

AU - Gana Weisz, Mali

AU - Bar-Shira, Anat

AU - Gurevich, Tanya

AU - Orr-Urtreger, Avi

AU - Alcalay, Roy N.

AU - Giladi, Nir

AU - Bregman, Noa

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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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SN - 0885-3185

JO - Movement Disorders

JF - Movement Disorders

ER -

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

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