Objective: To evaluate the prevalence of and associations between potential markers of premotor Parkinson’s disease (PD) and to estimate the relative risk of these markers according to PD family history.

Background: At the time of PD diagnosis, patients have typically already experienced substantial neuronal loss. Therapeutics therefore might be more effective if initiated earlier in the disease process before clinical signs emerge. Evidence suggests that PD is preceded by a prodromal period characterized by non-motor symptoms. Based on the results of a pilot study, the co-occurrence of constipation, probable REM sleep behavior disorder (pRBD) and hyposmia is associated with an approximately 200 fold increase in PD risk, suggesting they could be used to screen for premotor PD.

Methods: We are conducting a large longitudinal investigation to identify individuals in the premotor phase of PD using data from the Health Professionals Follow-up Study, a cohort of 51,529 men with health-related data updated biannually via mailed questionnaires. We selected all individuals (N=5782) without a PD diagnosis who had responded yes to screening questions for either constipation or pRBD, as well as a random sample of 3,000 individuals who had screened negative for constipation and pRBD and 149 confirmed PD cases. These participants were mailed questionnaires regarding PD symptoms, other possible signs of premotor PD (excessive daytime sleepiness, impaired color discrimination), and Brief Smell Identification Tests to assess hyposmia. We are now following all participants for new onset of PD.

Results: We received 6,595 complete responses for a response rate of 74%. Based on preliminary results from initial responders, we identified 163 people with hyposmia, pRBD and constipation, 699 with two of these markers, 2,147 with one marker, and 1,785 with no markers. After controlling for age, we found significant associations between hyposmia and each of the other premotor signs under study. Constipation and pRBD were not significantly associated. PD family history was associated with an OR of 1.46 (95% CI 1.07, 1.99) for hyposmia, but not with other potential premotor signs.

Conclusions: Hyposmia is associated with higher odds of having other potential signs of premotor PD, as well as with PD family history. Future analyses in this cohort will evaluate whether combining hyposmia with other efficient, low-cost screening tools is useful for identifying people with premotor PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-premotor-parkinsons-disease/