Survival and dementia in GBA ‐associated Parkinson's disease: The mutation matters

The objective of this work was to investigate survival, dementia, and genotype‐phenotype correlations in patients with Parkinson's disease (PD) with and without mutations on the glucocerebrosidase gene (GBA).
MethodsWe included 2,764 unrelated consecutive PD patients: 123 GBA carriers (67 mild‐p.N370S and 56 severe mainly p.L444P) and 2,641 noncarriers. Brain perfusion and dopamine transporter imaging was analyzed, including dementia with Lewy Bodies (DLB) as an additional control group.
ResultsMultivariable analysis adjusted by sex, age at onset, and disease duration attributed to GBA carriers a greater risk for dementia (hazard ratio [HR] = 3.16; p < 0.001) and death (HR = 1.85; p = 0.002) than noncarriers. When dementia was introduced in the model as a time‐dependent covariate, the mortality risk remained greater in carriers (HR = 1.65; p = 0.016), suggesting that other clinical features are likely to contribute to reduced survival. At last examination, GBA carriers had worse motor symptoms, particularly nondopaminergic features. Carriers of severe mutations had greater risk for dementia compared to mild mutations (p < 0.001), but similar mortality risk. Consistent with clinical data, GBA carriers showed reduced posterior parietal and occipital cortical synaptic activity and nigrostriatal function than PD noncarriers. Neuroimaging features of carriers of mild mutations overlapped with PD noncarriers, whereas carriers of severe mutati...

Source: Annals of Neurology - October 2, 2016 Category: Neurology Authors: Roberto Cilia, Sara Tunesi, Giorgio Marotta, Emanuele Cereda, Chiara Siri, Silvana Tesei, Anna L. Zecchinelli, Margherita Canesi, Claudio B. Mariani, Nicoletta Meucci, Giorgio Sacilotto, Michela Zini, Michela Barichella, Corrado Magnani, Stefano Duga, Ros Tags: Research Article Source Type: research