Truncal vagotomy may be associated with a reduced risk of incident Parkinson’s disease, according to data published online ahead of print April 26 in Neurology. Selective vagotomy, however, is not associated with risk of Parkinson’s disease. These findings provide support for the theory that Parkinson’s disease begins in the gut and spreads to the brain via the vagus nerve, according to the authors.
Braak et al have hypothesized that Lewy pathology in Parkinson’s disease may start in peripheral nerves, such as the enteric nervous system, and spread to the CNS in a way similar to the propagation of prions. Researchers have found Lewy-type deposition in the gut of people with prodromal Parkinson’s disease. In addition, resection of the vagus nerve before administration of rotenone, which prompts alpha-synuclein accumulation, stopped the spread of parkinsonian pathology in mice.
Bojing Liu
To examine whether vagotomy decreases the risk of Parkinson’s disease, Bojing Liu, a doctoral student at the Karolinska Institutet in Stockholm, and colleagues conducted a matched-cohort study using data from nationwide Swedish registers. The investigators identified 9,430 patients who underwent vagotomy (3,445 truncal, 5,978 selective, and seven unknown) between 1970 and 2010. Eligible participants were born before 1970 and lived in Sweden without a diagnosis of Parkinson’s disease before vagotomy. To each of these patients, the researchers individually matched 377,200 reference individuals from the general population by sex and year of birth in a 40:1 ratio. Participants were followed up from the date of vagotomy until Parkinson’s disease diagnosis, death, emigration out of Sweden, or December 31, 2010, whichever occurred first.
Participants’ mean age at index date was 54. The investigators identified 4,930 cases of Parkinson’s disease during follow-up, and mean age at diagnosis was 76. Although the study groups were otherwise well balanced, proportionally more patients who underwent vagotomy were born outside Sweden, compared with controls. Participants who underwent truncal vagotomy were older than those who underwent selective vagotomy and older than controls.
Ms. Liu and colleagues did not find an association between vagotomy and Parkinson’s disease overall. They did, however, observe a lower risk of Parkinson’s disease more than five years after truncal vagotomy (hazard ratio [HR], 0.59) and more than 10 years after truncal vagotomy (HR, 0.62). Selective vagotomy was not associated with Parkinson’s disease risk in any of the analyses.
“Our observation of the temporal relationship is consistent with the possibility that Parkinson’s disease pathology may start at multiple sites of the peripheral nervous system. Therefore, even truncal vagotomy may delay rather than eliminate the risk for Parkinson’s disease,” said Ms. Liu and colleagues. She acknowledged that she and her colleagues were unable to control for potential individual confounders such as smoking, coffee consumption, or genetic factors.
“If the observed association is confirmed and proven to be biologic, we expect the results could be generalized to populations in other parts of the world,” Ms. Liu continued. “These data provide preliminary and indirect support for the Braak and prion-like hypotheses for Parkinson’s disease prodromal development.”
—Erik Greb
Suggested Reading
Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology. 2017 Apr 26 [Epub ahead of print].