ArticleAnnals of neurology2016
Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.
Article in Annals of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 4 of them syntheses that pooled it.
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Who cites it
165 citing papers in PubMed, 4 syntheses or guidelines pooled it, 273 citations in OpenAlex.
- Association between the LRP1B and APOE loci and the development of Parkinson's disease dementia.Brain : a journal of neurology · 2023Pooled it
- Neurodevelopmental Clues to Neurodegeneration.Pediatric neurology · 2021Pooled it
- Trends in Glucocerebrosides Research: A Systematic Review.Frontiers in physiology · 2020Pooled it
- Emerging links between pediatric lysosomal storage diseases and adult parkinsonism.Movement disorders : official journal of the Movement Disorder Society · 2019Pooled it
- A Randomized, Double-Blinded, Placebo-Controlled QTc Study to Evaluate BIA 28-6156 Effect on Cardiac Repolarization in Healthy Volunteers.Clinical pharmacology in drug development · 2026Trial
- Faster disease progression in Parkinson's disease with glucocerebrosidase genotype: But not apparent immediate from diagnosis.Journal of Parkinson's disease · 2025Trial
- Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients with Parkinson's Disease and a GBA Mutation: Results from Part 1 of the Randomized, Double-Blinded, Placebo-Controlled MOVES-PD Trial.Journal of Parkinson's disease · 2022Trial
- Does genetic testing remain relevant in advanced Parkinson's disease?Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Cognition endpoints for Parkinson's disease: A roadmap for developing patient-focused assessment tools to accelerate drug development.Journal of Parkinson's disease · 2026Article
- Clinical Trials in GBA1-Associated Parkinson's Disease: A Need for Molecular Classification.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Genetic and Pathological Testing Attitudes for Parkinson's Disease in At-Risk Relatives.Movement disorders clinical practice · 2026Article
- Multi-locus genetic dosage shapes cognitive disease progression in Parkinson's patients: 15-year meta-analysis of 24 cohorts.NPJ Parkinson's disease · 2026Article
- Motor and Cognitive Outcome After Subthalamic Nucleus Deep Brain Stimulation in Patients with Parkinson's Disease Harboring GBA1 Variant.Movement disorders clinical practice · 2026Article
- The interplay between GBA1 status and age of onset on cognitive, motor and non-motor outcomes in Parkinson's disease: multicenter cross-sectional study.Journal of neurology · 2026Article
- Progression ofFrontiers in aging neuroscience · 2026Article
- Dairy-rich diet triggers hepatic α-synuclein pathology via the liver-brain axis in GBA1-related Parkinson's disease.NPJ Parkinson's disease · 2025Article
- GBA1 Gene-Associated Transcriptomic Signatures Reveal Risk Genes in Parkinson's Disease.Biomedicines · 2025Article
- Modelling cholinergic and dopaminergic function over time in Parkinson's disease with and without GBA1 variants.NPJ Parkinson's disease · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Severe GBA1 variants drive the GBA1-PD clinical phenotype: implications for counselling and clinical trials.NPJ Parkinson's disease · 2025Article
105 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 11 institutions in 5 countries.
Funding
Abstract
objectiveWe hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates.
methodsA total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models.
resultsOverall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60-6.25) and a hastened decline in Mini-Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18-8.73; p = 0.022). By contrast, the common, non-neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92-4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89-2.05) did not reach significance.
interpretationMutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into "high gear." These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674-685.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.