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Abstracts & Commentary
Sources: Ascherio A, et al. Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol. 2001;50:56-63; Chen J, et al. Neuroprotection by caffeine and A2A adenosine receptor inactivation in a model of Parkinson’s disease. J Neurosci. 2001;21:RC143.
Several recent studies have reported an inverse association between caffeine consumption and the risk of Parkinson’s disease (PD). This subject is of considerable interest to neurologists and patients (not to mention shareholders in Starbucks). Does consumption of coffee lower the risk of developing PD? Or do patients who may be at risk of developing the disease simply drink less coffee? By what mechanism could caffeine exert its effect? Two recent papers offer compelling testimony that caffeine consumption may be truly neuroprotective, and, further, offer a credible scientific explanation for caffeine’s possible protective effect on the dopaminergic system.
Ascherio and colleagues examined 2 large cohorts of individuals followed prospectively over many years, the Health Professionals’ Follow-up Study (HPFS) and the Nurses’ Health Study (NHS). The HPFS followed 47,351 male health professionals for 9.2 years, and the NHS followed 88,565 female registered nurses for 15.5 years. Participants answered detailed questionnaires every 2 years on a variety of topics, including diet, lifestyle, and health status. Caffeine intake from coffee, tea, caffeinated beverages, and chocolate was assessed.
One hundred fifty-seven male cases of PD and 131 female cases were documented. Once patients were identified, their medical records from their treating neurologist were reviewed to ensure that the diagnosis was correct. In both groups, coffee consumption was strongly associated with a decreased risk of PD. For both men and women, the relative risk was 0.6 for individuals who smoked in the past, and 0.4 for current smokers. Among men, the quantity of daily coffee consumption was inversely proportional to the risk of development of PD, while in women there was a U-shaped relation between coffee consumption and risk of PD (with the lowest risk at 1-3 cups per day). Among men, the inverse association between caffeine and Parkinson’s held regardless of the source of the caffeine.
One possible explanation for these results is that patients at risk for developing PD are also less likely to drink coffee. Because caffeine exerts its stimulatory effect through the dopaminergic system, this possibility cannot be excluded. An alternative and more intriguing possibility is that caffeine consumption may actually be neuroprotective. In their recent paper (published as a rapid communication online), Chen and colleagues offer a possible mechanism for caffeine’s putative neuroprotective action.
Caffeine is a potent antagonist at the A1 and A2A subtypes of the adenosine receptors. Expression of the A2A receptor is restricted to the striatum, the target of dopaminergic neurons. Using the MPTP model of PD, mice exposed to MPTP reliably develop profound dopaminergic depletion. Pretreating mice with low-dose caffeine (similar to the amount imbibed by a human in a cup of coffee) significantly attenuated dopaminergic depletion by MPTP. By using A1 and A2A adenosine receptor antagonists, Ascherio et al were able to demonstrate that this effect was mediated by A2A receptors and not A1 receptors. Also, knock-out mice lacking the A2A receptor were protected against MPTP, suggesting that either genetic or pharmacologic antagonism of the A2A receptor can effectively attenuate MPTP-induced dopaminergic depletion. These results offer a biologic mechanism whereby caffeine could exert its neuroprotective effect. While the MPTP model has limitations as an experimental model of PD, these results are compelling.
What should neurologists tell their patients about caffeine consumption? At the very least, these results seem to indicate that coffee consumption by the general public may offer protection against the development of PD. For patients diagnosed with PD, consumption of 1-3 cups of coffee per day, for those who like coffee or who are already drinking it, seems a reasonable approach. —Steven Frucht