Coffee, smoking and aspirin are associated with age at onset and clinical severity in idiopathic Parkinson's disease

Parkinsons disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene-environment interactions have been found to modify PD risk and disease progression. The objective of this study was to evaluate the association of smoking, caffeine and anti-inflammatory drugs with age at onset (AAO) and clinical severity in a large PD cohort. A total of 35,963 American patients with idiopathic PD (iPD) from the Fox Insight Study responded to health and lifestyle questionnaires. We compared the median AAO between different groups using the non-parametric Mann-Whitney U test. Non-parametric Spearman correlation was used for correlation assessments and regression analysis was used to assess interaction between variables. Reported p-values remain descriptive because they are not corrected for multiple testing and results are exploratory. We found that smoking (r=0.08, p<0.0001), coffee drinking (r=0.69, p<0.0001) and aspirin intake (r=0.23, p<0.0001) show an exploratory association with AAO in iPD. However, the effect of aspirin diminished as an independent predictor after including comorbidities (heart diseases and arthritis). Smoking was associated with higher (more severe) motor scores, while coffee drinking was linked to lower (less severe) motor scores (p<0.05). In addition, smokers reported anxiety, depression and other non-motor symptoms such as unexplained pains and problems remembering (p<0.05). The association of aspirin with PD AAO was replicated in another cohort (EPIPARK) (n=237 patients with PD), although again the effect diminished after including age in the regression model. Future longitudinal studies are warranted to investigate the clinical severity over time.