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People with Parkinson's disease had lower plasma caffeine levels than people without Parkinson's, and levels were even lower for Parkinson's patients carrying the LRRK2 gene mutation, researchers reported.

Plasma caffeine concentration was lower in Parkinson's patients compared with healthy controls, substantially more so among LRRK2 carriers (by 76%) than noncarriers (by 31%), reported Grace Crotty, MD, of Massachusetts General Hospital in Boston, and co-authors, in .

"These results are promising and encourage future research exploring caffeine and caffeine-related therapies to lessen the chance that people with this gene develop Parkinson's," Crotty said in a statement. "It's also possible that caffeine levels in the blood could be used as a biomarker to help identify which people with this gene will develop the disease, assuming caffeine levels remain relatively stable."

While the leucine-rich repeat kinase 2 (LRRK2) mutation is considered a causative influence on Parkinson's, people who carry the gene do not necessarily develop the disease.

Previous reports have suggested an inverse association between daily caffeine consumption and reduced risk of developing Parkinson's.

"It's odd that non-LRRK2 carriers had no association with caffeine in this study," noted Ron Postuma, MD, MSc, of McGill University in Montreal, who wasn't involved with the research.

"This is quite different than other studies," he told 口袋女优. "Even if those other studies didn't assess LRRK2 status, there are not enough noncarriers in general cohorts to account for the strong links with caffeine seen from so many different populations."

Other studies, including the CafePD trial led by Postuma, have shown caffeine doesn't help Parkinson's motor disorders.

"In our randomized trial of caffeine and Parkinson's disease, we found no benefit of caffeine on motor symptoms of Parkinson's disease," he said. "We did not see any trend towards long-term improvement like you might see with neuroprotective effects, but the study was not designed or powered to test neuroprotection."

In this analysis, Crotty and co-authors set out to identify markers of resistance to developing Parkinson's disease among LRRK2 mutation carriers by profiling metabolites in 188 Parkinson's patients and 180 healthy controls. Both groups had people with and without the LRRK2 gene mutation.

Samples came from the of the Michael J. Fox Foundation for Parkinson's Research. Plasma samples included 118 LRRK2 carriers and 70 noncarriers in the Parkinson's disease group, and 115 carriers and 65 noncarriers in the control group. Cerebrospinal fluid (CSF) samples were available for 68 participants. A total of 212 participants also completed dietary caffeine questionnaires.

Plasma caffeine concentration was lower in Parkinson's patients compared with controls (P<0.001), especially LRRK2 carriers, with a significant interaction between LRRK2 and Parkinson's status (P=0.005). Similar results were seen for caffeine metabolites paraxanthine, theophylline, 1-methylxanthine, and a non-xanthine marker of coffee consumption (trigonelline) in plasma, and in corresponding CSF samples.

Dietary caffeine was also lower in LRRK2 carriers with Parkinson's compared with carriers in the control group, with significant interaction effect with the LRRK2 mutation (P<0.001).

"We don't know yet whether people who are predisposed to Parkinson's may tend to avoid drinking coffee or if some mutation carriers drink a lot of coffee and benefit from its neuroprotective effects," Crotty noted.

The study has several limitations, the researchers said. Potential selection bias may have occurred and unmeasured confounders may have influenced results. The study also looked at people only at one point in time and does not prove caffeine consumption lowers Parkinson's risk, Crotty pointed out.

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