Effects of caffeine in Parkinson's disease: from neuroprotection to the management of motor and non-motor symptoms.

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population older than 60 years. Classically, PD is considered to be a motor system disease and its diagnosis is based on the presence of a set of cardinal motor signs (rigidity, bradykinesia, rest tremor) that are consequence of a pronounced death of dopaminergic neurons in the substantia nigra pars compacta. Nowadays there is considerable evidence showing that non-dopaminergic degeneration also occurs in other brain areas which seems to be responsible for the deficits in olfactory, emotional and memory functions that precede the classical motor symptoms in PD. The present review attempts to examine results reported in epidemiological, clinical and animal studies to provide a comprehensive picture of the antiparkinsonian potential of caffeine. Convergent epidemiological and pre-clinical data suggest that caffeine may confer neuroprotection against the underlying dopaminergic neuron degeneration, and influence the onset and progression of PD. The available data also suggest that caffeine can improve the motor deficits of PD and that adenosine A2A receptor antagonists such as istradefylline reduces OFF time and dyskinesia associated with standard 'dopamine replacement' treatments. Finally, recent experimental findings have indicated the potential of caffeine in the management of non-motor symptoms of PD, which do not improve with the current dopaminergic drugs. Altogether, the studies reviewed provide strong evidence that caffeine may represent a promising therapeutic tool in PD, thus being the first compound to restore both motor and non-motor early symptoms of PD together with its neuroprotective potential.