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

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.