Age at onset as stratifier in idiopathic Parkinson's disease – effect of ageing and polygenic risk score on clinical phenotypes
Lukas Pavelka, Armin Rauschenberger, Zied Landoulsi, Sinthuja PACHCHEK, Patrick May, Enrico Glaab, , Rejko Krueger on behalf of the NCER-PD Consortium
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 son 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.
The datasets for this manuscript are not publicly available as they are linked to the Luxembourg Parkinson’s Study and its internal regulations. Requests to access the datasets should be directed to the Executive Committee of NCER-PD, mean of contact via email: firstname.lastname@example.org.
The source code is available here.