Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Pavelka, L. and Rauschenberger, A. and Landoulsi, Z. and Pachchek, S. and May, P. and Glaab, E. and Krüger, R. and and on behalf of the NCER-PD Consortium*, : and Acharya, Geeta and Aguayo, Gloria and Alexandre, Myriam and Ali, Muhammad and Allen, Dominic and Ammerlann, Wim and Balling, Rudi and Bassis, Michele and Beaumont, Katy and Becker, Regina and Bellora, Camille and Berchem, Guy and Berg, Daniela and Bisdorff, Alexandre and Brockmann, Kathrin and Calmes, Jessica and Castillo, Lorieza and Contesotto, Gessica and Diederich, Nico and Dondelinger, Rene and Esteves, Daniela and Fagherazzi, Guy and Ferrand, Jean-Yves and Gantenbein, Manon and Gasser, Thomas and Gawron, Piotr and Ghosh, Soumyabrata and Glaab, Enrico and Gomes, Clarissa and Gómez De Lope, Elisa and Goncharenko, Nikolai and Graas, Jérôme and Graziano, Mariella and Groues, Valentin and Grünewald, Anne and Gu, Wei and Hammot, Gaël and Hanff, Anne-Marie and Hansen, Linda and Hansen, Maxime and Heneka, Michael and Henry, Estelle and Herbrink, Sylvia and Herbrink, Sylvia and Herenne, Eve and Herzinger, Sascha and Heymann, Michael and Hu, Michele and Hundt, Alexander and Jacoby, Nadine and Lebioda, Jacek Jaroslaw and Jaroz, Yohan and Klopfenstein, Quentin and Krüger, Rejko and Lambert, Pauline and Landoulsi, Zied and Lentz, Roseline and Liepelt, Inga and Liszka, Robert and Longhino, Laura and Lorentz, Victoria and Lupu, Paula Cristina and Mackay, Clare and Maetzler, Walter and Marcus, Katrin and Marques, Guilherme and Marques, Tainá and May, Patrick and Mcintyre, Deborah and Mediouni, Chouaib and Meisch, Francoise and Menster, Myriam and Minelli, Maura and Mittelbronn, Michel and Mollenhauer, Brit and Mommaerts, Kathleen and Moreno, Carlos and Moudio, Serge and Mühlschlegel, Friedrich and Nati, Romain and Nehrbass, Ulf and Nickels, Sarah and Nicolai, Beatrice and Nicolay, Jean-Paul and Oertel, Wolfgang and Ostaszewski, Marek and Pachchek, Sinthuja and Pauly, Claire and Pauly, Laure and Pavelka, Lukas and Perquin, Magali and Lima, Roslina Ramos and Rauschenberger, Armin and Rawal, Rajesh and Rosales, Eduardo and Rosety, Isabel and Rump, Kirsten and Sandt, Estelle and Satagopam, Venkata and Schlesser, Marc and Schmitt, Margaux and Schmitz, Sabine and Schneider, Reinhard and Schwamborn, Jens and Sharify, Amir and Soboleva, Ekaterina and Sokolowska, Kate and Terwindt, Olivier and Thien, Hermann and Thiry, Elodie and Ting Jiin Loo, Rebecca and Trefois, Christophe and Trouet, Johanna and Tsurkalenko, Olena and Vaillant, Michel and Valenti, Mesele and Vilas Boas, Liliana and Vyas, Maharshi and Wade-Martins, Richard and Wilmes, Paul (2022) Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes. npj Parkinson's Disease, 8 (102). pp. 1-10. ISSN 2373-8057 (online)

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Abstract

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients.

Item Type: Article
Additional Information: https://www.nature.com/articles/s41531-022-00342-7#citeas
Subjects: Neurological disease
Divisions: Faculty of Postgraduate Education > Department of Neurology and Neurosurgery FPE
Depositing User: Елена Шрамко
Date Deposited: 31 Aug 2022 12:13
Last Modified: 08 Sep 2022 11:50
URI: http://repo.dma.dp.ua/id/eprint/7808

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