Abstract
The COMT Val158Met polymorphism has recently been identified as a predictor for cognitive decline in Parkinson’s disease (PD). However, it remains unknown whether an early brain structural compromise could be involved in this clinical association. Here, in a cohort of 120 cognitively preserved de novo PD patients from the Parkinson’s Progression Markers Initiative (PPMI) database, we found a widespread reduction in cerebral gray matter volume (GMV) in patients harboring the Val/Val genotype. The atrophic pattern included fronto-subcortical and parieto-temporal territories. Importantly, the GMV at some of the identified regions was associated with cognitive decline in a 4-year follow-up period. These findings suggest that GMV compromise in the early stages of PD may be a predisposing factor for cognitive decline of COMT Val/Val homozygotes.
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Acknowledgements
Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org.
PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbvie, Avid Radiopharmaceuticals, Biogen Idec, BioLegend, Bristol-Myers Squibb, Eli Lilly & Co., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale Discovery, Pfizer, Piramal, Roche, Sanofi Genzyme, Servier, Takeda, Teva, and UCB.
Funding
This work was partially supported by CERCA and CIBERNED funding, and grants from la Marató de TV3 (2014/U/477 and 20142910) and Fondo de Investigaciones Sanitarias del Ministerio de Sanidad y Consumo (PI15/00962 and PI14/02058).
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Frederic Sampedro declares that he has no conflict of interest. Juan Marín-Lahoz declares that he has no conflict of interest. Saul Martínez-Horta declares that he has no conflict of interest. Javier Pagonabarraga declares that he has no conflict of interest. Jaime Kulisevsky declares that he has no conflict of interest.
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Figure S1
Reduced gray matter volume of COMT Val/Val HC subjects with respect to HC Met carriers (p < 0.005 uncorrected, minimum cluster size of 100 voxels). No significant regions of increased gray matter volume were obtained. No clusters survived p < 0.05 FWE cluster-level correction. (PNG 1072 kb)
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Sampedro, F., Marín-Lahoz, J., Martínez-Horta, S. et al. Reduced gray matter volume in cognitively preserved COMT 158Val/Val Parkinson’s disease patients and its association with cognitive decline. Brain Imaging and Behavior 14, 321–328 (2020). https://doi.org/10.1007/s11682-018-0022-y
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DOI: https://doi.org/10.1007/s11682-018-0022-y