Funding agencies: This work was supported by a research grant from CIBERNED and by the Fondo de Investigaciones Sanitarias (PI09/00098 and PI07/1150). Also, this work has been developed in the framework of the Spanish MICINN (CGL2009-12703-C03-02, SAF2010-17589, and SAF2011-25431), and the Catalan AGAUR (2009SGR-188 and 2009SGR-971).
Version of Record online: 15 DEC 2011
Copyright © 2011 Movement Disorder Society
Volume 27, Issue 3, pages 393–399, March 2012
How to Cite
Setó-Salvia, N., Pagonabarraga, J., Houlden, H., Pascual-Sedano, B., Dols-Icardo, O., Tucci, A., Paisán-Ruiz, C., Campolongo, A., Antón-Aguirre, S., Martín, I., Muñoz, L., Bufill, E., Vilageliu, L., Grinberg, D., Cozar, M., Blesa, R., Lleó, A., Hardy, J., Kulisevsky, J. and Clarimón, J. (2012), Glucocerebrosidase mutations confer a greater risk of dementia during Parkinson's disease course. Mov. Disord., 27: 393–399. doi: 10.1002/mds.24045
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue online: 12 MAR 2012
- Version of Record online: 15 DEC 2011
- Manuscript Accepted: 24 OCT 2011
- Manuscript Revised: 18 OCT 2011
- Manuscript Received: 21 JUL 2011
- Parkinson's disease;
- Lewy body disease;
Mutations in the glucocerebrosidase gene are associated with Parkinson's disease and Lewy body dementia. However, whether these alterations have any effect on the clinical course of Parkinson's disease is not clear. The glucocerebrosidase coding region was fully sequenced in 225 Parkinson's disease patients, 17 pathologically confirmed Lewy body dementia patients, and 186 controls from Spain. Twenty-two Parkinson's disease patients (9.8%) and 2 Lewy body dementia patients (11.8%) carried mutations in the glucocerebrosidase gene, compared with only 1 control (0.5%); P = .016 and P = .021 for Parkinson's disease and Lewy body dementia, respectively. The N370S and the L444P mutations represented 50% of the alterations. Two novel variants, L144V and S488T, and 7 previously described alterations were also found. Alterations in glucocerebrosidase were associated with a significant risk of dementia during the clinical course of Parkinson's disease (age at onset, years of evolution, and sex-adjusted odds ratio, 5.8; P = .001). Mutation carriers did not show worse motor symptoms, had good response to L-dopa, and tended to present the intermediate parkinsonian phenotype. Our findings suggest that mutations in the glucocerebrosidase gene not only increase the risk of both Parkinson's disease and Lewy body dementia but also strongly influence the course of Parkinson's disease with respect to the appearance of dementia. © 2011 Movement Disorder Society