Concurrent Non-Motor Functions Strongly Associated With Parkinson Disease

Early detection of patients in the prodromal phase of Parkinson disease improves time to initiation of neuroprotective therapies.

Non-motor functions including constipation, hyposmia, and rapid eye movement sleep behavior disorder have shown strong associations with Parkinson disease, according to a study published in the Journal of Neurology, Neurosurgery, and Psychiatry.

This study included a large cohort of men recruited in 1986 who were aged between 40 and 75 at baseline. There were 120 confirmed cases of Parkinson disease, all participants were aged less than 85 as of January 2012. Among those with Parkinson disease, 29.3% experienced concurrent rapid eye movement sleep behavior disorder, constipation, and hyposmia, while only 1.1% of controls experienced this combination. For all three of these features vs none, the age-adjusted odds ratio was 160 (95% CI, 72.8-353.0). There was an exponential increase in the odds of Parkinson disease when more non-motor features were added, with an odds ratio of 1325 for 6 to 7 features compared with none (95% CI, 333-5279).

Men who did not have Parkinson disease showed increased odds of diagnosis with additional non-motor features, with an odds ratio of 89 for 6 to 7 features compared with none (95% CI, 21.2-375). A population with a 2% rate of Parkinson disease was estimated to show a positive predictive value of 35% and a maximum sensitivity of 29% with concurrent rapid eye movement sleep behavior disorder, constipation, and hyposmia. Additional features could increase the positive predictive value to 70%, although this would result in a dramatic decrease in sensitivity.

This case-control study was performed within the Health Professionals Follow-up Study. Confirmed cases completed a questionnaire in 2012 concerning constipation and rapid eye movement sleep behavior disorder. In addition, in 2014 they completed the Brief Smell Identification Test and a questionnaire related to Parkinson disease, including symptoms of depression, impaired color vision, extreme sleepiness during daytime, and pain. The same criteria were met by controls, except for a diagnosis of Parkinson disease.

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The study researchers conclude that “[concurrent] constipation, probable [rapid eye movement sleep behavior disorder] and hyposmia are strongly associated with [Parkinson disease]. Because these features often precede motor symptoms and their co-occurrence could provide an efficient method for early [Parkinson disease] identification.”


Hughes KC, Gao X, Baker JM, et al. Non-motor features of Parkinson’s disease in a nested case-control study of US men [published online August 3, 2018]. J Neurol Neurosurg Psychiatry. doi: 10.1136/jnnp-2018-318275.