Caffeine and Parkinson disease
A possible diagnostic and pathogenic breakthrough
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Most cases of Parkinson disease (PD) over age 50 are sporadic, and twin studies strongly suggest a predominance of environmental over genetic etiologies.1 However, few factors have been found consistently in epidemiologic studies to have major effects, protective in all cases: smoking, urate,2 and caffeine consumption.3 The protective effect of caffeine (found not only in coffee, but also in tea, and some sodas) has been demonstrated in large prospectively followed populations of men, with a dramatic reduction in risk (up to fivefold for persons who drank more than 4 cups of coffee a day). Decaffeinated coffee afforded no protection, pointing to caffeine rather than other substances in coffee or tea as the underlying pharmacologic agent. No such linear relationship is found in women, in whom the protective effects are either nonexistent or U-shaped.4 Caffeine’s protective effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced parkinsonism in experimental models is generally considered supportive evidence.5 A randomized controlled trial of caffeine for treatment of PD found improved motor manifestations at 6 weeks in secondary analyses, but not the hypothesized improvement in excessive daytime sleepiness. Caffeine is an antagonist at adenosine 2A receptors (A2A-R) located exclusively in the striatum, and specifically in medium spiny neurons coexpressing D2 dopamine receptors, a critical link in the indirect motor pathway. A plausible model can be proposed by which blockade of adenosine receptors would protect dopaminergic neurons in the substantia nigra from excitotoxic injury.6 Several randomized controlled trials have confirmed the efficacy of istradefylline, a selective A2A-R antagonist, to reduce “off” time and to improve motor manifestations of PD.7 Thus, exploring the mechanisms by which caffeine may protect against PD is a worthwhile endeavor.
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Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial.
Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease 218
- © 2018 American Academy of Neurology
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