TY - JOUR
T1 - Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes
AU - Pavelka, L.
AU - Rauschenberger, A.
AU - Landoulsi, Z.
AU - Pachchek, S.
AU - May, P.
AU - Glaab, E.
AU - Krüger, R.
AU - Acharya, Geeta
AU - Aguayo, Gloria
AU - Alexandre, Myriam
AU - Ali, Muhammad
AU - Allen, Dominic
AU - Ammerlann, Wim
AU - Balling, Rudi
AU - Bassis, Michele
AU - Beaumont, Katy
AU - Becker, Regina
AU - Bellora, Camille
AU - Berchem, Guy
AU - Berg, Daniela
AU - Bisdorff, Alexandre
AU - Brockmann, Kathrin
AU - Calmes, Jessica
AU - Castillo, Lorieza
AU - Contesotto, Gessica
AU - Diederich, Nico
AU - Dondelinger, Rene
AU - Esteves, Daniela
AU - Fagherazzi, Guy
AU - Ferrand, Jean Yves
AU - Gantenbein, Manon
AU - Gasser, Thomas
AU - Gawron, Piotr
AU - Ghosh, Soumyabrata
AU - Glaab, Enrico
AU - Gomes, Clarissa
AU - De Lope, Elisa Gómez
AU - Hanff, Anne Marie
AU - Hansen, Maxime
AU - Krüger, Rejko
AU - Lambert, Pauline
AU - Lorentz, Victoria
AU - Lupu, Paula Cristina
AU - Mittelbronn, Michel
AU - Mommaerts, Kathleen
AU - Nehrbass, Ulf
AU - Nickels, Sarah
AU - Pauly, Laure
AU - Perquin, Magali
AU - Sandt, Estelle
AU - Schmitt, Margaux
AU - Sokolowska, Kate
AU - Thien, Hermann
AU - Vaillant, Michel
AU - on behalf of the NCER-PD Consortium
N1 - Funding Information:
We would like to give special thanks to all participants in the Luxembourg Parkinson’s Study. Furthermore, we acknowledge the joint effort of the NCER-PD consortium members generally contributing to the Luxembourg Parkinson’s Study as listed below. The work presented here was supported within the framework of the National Centre of Excellence in Research on Parkinson’s Disease (NCER-PD) funded by the Luxembourg National Research Fund (FNR/NCER13/BM/11264123), the PEARL program (FNR/P13/6682797 to R.K.), MotaSYN (12719684 to R.K.), MAMaSyn (to R.K.), MiRisk‐PD (C17/BM/11676395 to R.K., E.G., P.M.), the FNR/DFG Core INTER (ProtectMove, FNR11250962 to P.M.), and the PARK-QC DTU (PRIDE17/12244779/PARK-QC to R.K. and S.P.), FNR PD-Strat (INTER/11651464 to EG), DIGIPD (ERAPERMED 2020-314 to EG).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/8/9
Y1 - 2022/8/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85135858183&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/35945230
U2 - 10.1038/s41531-022-00342-7
DO - 10.1038/s41531-022-00342-7
M3 - Article
C2 - 35945230
SN - 2373-8057
VL - 8
JO - npj Parkinson's Disease
JF - npj Parkinson's Disease
IS - 1
M1 - 102
ER -