GBA Mutations in Parkinson's May Increase Risk of Dementia

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GBA Mutations in Parkinson's May Increase Risk of Dementia
GBA Mutations in Parkinson's May Increase Risk of Dementia

HealthDay News -- Parkinson's disease (PD) patients with glucocerebrosidase gene (GBA) mutations have increased risk for dementia and death, according to a study published in the Annals of Neurology.

Roberto Cilia, MD, from the Parkinson Institute in Milan, and colleagues examined survival, dementia, and genotype-phenotype correlations in 2764 unrelated PD patients, including 123 GBA carriers and 2641 non-carriers. They analyzed brain perfusion and dopamine transporter imaging, including dementia with Lewy bodies (DLB) as an additional control group.

The researchers found that GBA carriers were at greater risk for dementia and death (hazard ratios, 3.16 and 1.85, respectively) than non-carriers in multivariable analysis adjusted by gender, age at onset, and disease duration. The mortality risk remained greater in carriers when dementia was introduced as a time-dependent covariate in the model (hazard ratio, 1.65). GBA carriers had worse motor symptoms, especially non-dopaminergic features, at last examination. The risk for dementia was increased for carriers of severe vs mild mutations; mortality risk was similar. Compared with PD non-carriers, GBA carriers exhibited reduced posterior parietal and occipital cortical synaptic activity and nigrostriatal function. Mild mutation carriers had neuroimaging features that overlapped with PD non-carriers, while carriers of severe mutations were more similar to DLB.

"Survival is reduced in GBA carriers compared to non-carriers; this seems to be partially independent from the increased risk for early dementia," the authors write.

Reference

Cilia R, Tunesi S, Marotta G, et al. Survival and dementia in GBA-associated Parkinson Disease: The mutation matters. Ann Neurol. 2016; doi:10.1002/ana.24777.

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