Caffeine: A Breakthrough for Diagnosing Parkinson Disease?

©Zadorozhna/Shutterstock

According to a study published online in Neurology, people with Parkinson disease (PD) have lower levels of caffeine and caffeine metabolites in their blood than healthy people.¹ Findings from the study suggest that caffeine may be a biomarker for PD, which could represent a breakthrough for diagnosing PD using a simple blood test.

“Previous studies have shown a link between caffeine and a lower risk of developing Parkinson disease, but we haven’t known much about how caffeine metabolizes within the people with the disease,” author Shinji Saiki, MD, PhD, of Juntendo University School of Medicine in Tokyo, Japan said in a press release.

Past studies have suggested that caffeine may have a neuroprotective effect in PD. Yet much remains unknown. For example, caffeine has been associated with improved motor symptoms in men but not in women with PD. And much about how genes and environment interact with caffeine in PD remains to be explored.²

Researchers used liquid chromatography-mass spectrometry to measure the levels of caffeine and 11 of its metabolites in the blood of 108 people with mild to moderate PD without dementia, along with 31 age-matched healthy people without PD. Researchers also did genetic analysis on 67 people with PD and 51 people without PD, to look for mutations in genes that influence caffeine metabolism. People with PD and healthy individuals had similar intake of caffeine, about two cups of coffee per day on average.

The results showed that people with PD had significantly decreased blood levels of caffeine (P < .0001) and 9 caffeine metabolites in PD (P < .0001-.0005). These levels were decreased even in people with early PD. The results were unrelated to sex, total caffeine intake, or disease severity. Furthermore, caffeine concentrations were significantly decreased in people with PD and motor complications compared with those who had PD without motor complications (P = .0132).

No significant differences were seen in caffeine-related genes in PD compared with healthy controls. Further analyses using all major caffeine metabolites showed that the area under the curve (AUC) was 0.98. Because a score of 1 indicates that a test identifies all cases of the disease, testing for all major caffeine metabolites has the potential to be highly accurate, according to the authors.

The authors also mention that having more severe PD was not linked to lower levels of caffeine, which suggests that decreased caffeine metabolism may occur even in early PD. “If these results can be confirmed, they would point to an easy test for early diagnosis of Parkinson, possibly even before symptoms are appearing,” David Munoz, MD, FRCPC, of the University of Toronto, and Shinsuke Fujioka, MD, of Fukuoka University, Japan, wrote in a related editorial.³

However, they brought up an “elephant in the room”: 98% of participants with PD were on anti-Parkinsonian medication. Further analysis showed no link between caffeine metabolite levels and levodopa equivalent doses, but that still does not answer whether caffeine metabolism was affected by anti-parkinsonian medication in this study. Further studies are needed, especially in persons with untreated PD or those with early prodromal PD. Confirmation of the results in such studies, would be of “enormous importance,” according to Drs Muniz and Fujioka, because it could provide a test for early or even preclinical PD.

Take Home Points
1. Single center Japanese study found that blood levels of caffeine and 9 caffeine metabolites were significantly decreased in individuals with PD compared with healthy controls.
2. Caffeine levels were decreased even in early PD and in people with motor complications.
3. There were no significant differences in caffeine-related genes in PD compared with healthy controls.
4. Caffeine and its metabolites may be biomarkers for PD, even early or preclinical PD, which may represent a potential diagnostic breakthrough.
5. Further studies are needed

Disclosures:

1. Fujimaki M, Saiki S, Li Y, et al. Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease. Neurology. January 2018; Epub ahead of print.
2. Hackethal V. Gene, caffeine, creatine: link to Parkinson disease. Neurology Times. May 2017. http://www.neurologytimes.com/parkinson-disease/gene-caffeine-creatine-link-parkinson-disease. Accessed January 18, 2018.
3. Munoz DG, Fujioka S. Caffeine and Parkinson disease: a possible diagnostic and pathogenic breakthrough. Neurology. January 2018; Epub ahead of print.