Affiliations: [a] Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
| [b] Harvard Medical School, Boston, MA, USA
| [c] Biostatistics Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| [c] Departments of Epidemiology and Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| [d] APDA Center for Advanced Parkinson Research, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| [e] Precision Neurology Program, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Correspondence to: Rachit Bakshi, PhD, Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street, Boston, MA 02129, USA. Tel.: +1 617 724 2575; Fax: +1 617 724 1480; E-mail: [email protected].
Note:  These authors contributed equally to this work.
Abstract: Two purines, caffeine and urate, have been associated with a reduced risk of idiopathic Parkinson’s disease (PD) in multiple cohorts and populations. The Harvard Biomarkers Study (HBS) is a longitudinal study designed to accelerate the discovery and validation of molecular diagnostic and progression markers of early-stage PD. To investigate whether these ‘reduced risk’ factors are associated with PD within this cohort, we conducted a cross-sectional, case-control study in 566 subjects consisting of idiopathic PD patients and healthy controls. Caffeine intake as assessed by a validated questionnaire was significantly lower in idiopathic PD patients compared to healthy controls in males (mean difference –125 mg/day, p < 0.001) but not in females (mean difference –30 mg/day, p = 0.29). A strong inverse association was also observed with plasma urate levels both in males (mean difference –0.46 mg/dL, p = 0.017) and females (mean difference –0.45 mg/dL, p = 0.001). Both analyses stratified for sex and adjusted for age, body mass index, and either urate level or caffeine consumption, respectively. These results highlight the robustness of caffeine intake and urate as factors inversely associated with idiopathic PD.