Objective: Explore whether age at onset of Parkinson’s disease influences the rate of early disease progression.

Background: In cross-sectional studies, older age at onset has been associated with greater disease severity and impairment of striatal DaTSCAN binding, but no longitudinal studies have evaluated how age at onset influences disease progression on clinical and imaging parameters.

Method: We analysed data from the Parkinson’s Progression Markers Initiative Database, including 423 patients with a diagnosis of PD confirmed by DaTSCAN imaging. Over a 60-month follow-up period, we investigated whether older age at onset was associated with faster motor progression, development of motor complications, cognitive decline and loss of striatal DaTSCAN binding. We used multivariate linear regression models to predict changes in each of the following outcome variables: severity of motor (MDS-UPDRS part II, part III and total), nonmotor symptoms (MDS-UPDRS part I questionnaire), motor complications (MDS-UPDRS part IV) and nigrostriatal function (DaTSCAN binding in putamen binding to ipsilateral to most affected clinical side). We included in the models the following covariates: age at onset, gender and years of education, H&Y stage, MDS-UPDRS, MoCA, presence of REM Behaviour disorder, DaTSCAN binding in putamen binding to contralateral to most affected clinical side, CSF levels of total alpha-synuclein, tau, p-tau and amyloid-beta_1-42.

Results: Older age at onset was associated with faster motor progression (change in MDS-UPDRS part III: p=0.011; change in MDS-UPDRS total: p=0.021), development of motor complications (change in MDS-UPDRS part IV: p=0.001), cognitive decline (change in MoCA: p<0.0001) and faster decline of nigrostriatal dysfunction (change in DaTSCAN putamen ipsilateral binding: p=0.002). Older age at onset was not associated with progression of motor or non-motor patient-reported activities of daily living (changes in MDS-UPDRS part II = p>0.10 and part I questionnaire = p>0.10; respectively).

Conclusion: Our findings confirm a direct contribution of the aging process to the progressive neurodegeneration of PD, which suggests that age at onset should be included as stratification factor in future clinical trials in patients with early PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/age-at-onset-and-parkinsons-disease-progression/