Objective: To assess the impact of GBA mutations and APOE polymorphisms on progression and survival in a cohort of Ashkenazi Jewish (AJ) patients with DLB.

Background: Cross-sectional studies have revealed that GBA mutations and the APOE ɛ4 allele have distinct effects on the clinical phenotype of dementia with Lewy bodies (DLB). The longitudinal clinical impact of these genetic factors has not clearly been elucidated in DLB.

Method: We included 114 DLB patients from an AJ cohort; 38 GBA mutation carriers and 76 non-carriers. The survival rate was analyzed with the Cox proportional hazard regression adjusted for gender and age at onset. The change in cognitive and motor status was assessed with the Mini-Mental State Examination and Unified Parkinson’s Disease Rating Scale, respectively, and analyzed with the mixed-effects linear regressions in a subset of patients.

Results: During the 2013-2021 period, 33 of the 114 subjects died, 15 of whom were GBA mutation carriers. Unadjusted analyses showed that death occurred at similar disease duration and age in GBA carriers compared to noncarriers. However, multivariable analysis performed after adjusting for sex and age at onset showed a significantly increased risk of death in GBA carriers compared to non-carriers (hazard ratio=2.86, p=0.004).  The rate of cognitive and motor deterioration was comparable in both groups.

Conclusion: Patients with DLB who carry GBA mutations have reduced survival but show similar cognitive and motor deterioration compared to non-carriers with no longitudinal effect of the APOE ε4 status.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/survival-and-progression-in-gba-associated-dementia-with-lewy-bodies/