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CHAPTER 7

Caffeine and Parkinson's Disease: From Molecular Targets to Epidemiology and Clinical Trials

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 1% of the world population age 65 and older. In the absence of an effective disease-modifying treatment for PD, epidemiological and experimental investigations into potential risk factors (such as dietary factor caffeine) that may allow individuals to decrease their risk become compelling. Caffeine, the most widely consumed psychoactive substance, exerts neurobiological effects mainly by blocking adenosine receptors. Four decades after the earliest attempt to treat PD using caffeine, now there is convergence of epidemiological evidence and animal evidence that raises the exciting possibility that adenosine receptor antagonists, including caffeine, may offer motor and non-motor as well as potential neuroprotective benefits. In particular, since 2000, at least six large prospective studies have firmly established a relationship between increased caffeine consumption and decreased risk of developing Parkinson's disease. Furthermore, since 2003, eight double-blind, placebo-controlled, clinical phase IIb and III trials of adenosine A2A receptor antagonists were conducted and reported to offer a modest but significant motor benefit. In addition, genetic and pharmacological studies in human and animal models have revealed novel potential of caffeine to improve non-motor symptoms, including sleep disturbance and cognitive impairments in PD. To realize therapeutic potential of caffeine in PD, we argue that caffeine consumption information should be incorporated into clinical trials for adenosine receptor-based therapy in PD and other CNS disorders. Importantly, genetic study of caffeine in the human population may identify useful pharmacogenetic markers for predicting individual responses to caffeine and A2AR antagonists in PD clinical trials and thus offer a unique opportunity for “personalized medicine” in PD.

Publication details


Print publication date
31 Jan 2019
Copyright year
2019
Print ISBN
978-1-78801-497-7
PDF eISBN
978-1-78801-502-8