Nonmotor symptoms and Parkinson disease in United States farmers and spouses

Objectives: Few studies have evaluated the presence of multiple nonmotor symptoms (NMS) in relation to Parkinson disease (PD). Therefore, we examined cross-sectional associations between individual and multiple NMS and PD in the Agricultural Health Study. Methods: 20,473 male farmers and 16,259 female spouses provided information on six NMS (reduced sense of smell, dream-enacting behavior, daytime sleepiness, infrequent bowel movement, depression, and anxiety) in the cohort’s 2013–2015 follow-up survey. 191 men and 68 women reported physician-diagnosed PD. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models separately by sex. Results: NMS were each associated with PD, with the strongest association for reduced sense of smell in men and dream-enacting behavior in women. The number of NMS showed a strong dose-response relationship with PD, particularly in men. ORs were 5.5 (95% CI 3.4–8.8) for one, 17 (95% CI 10.4–28.0) for two, and 53.4 (95% CI 33.2–86.1) for three or more NMS in men; the corresponding ORs were 4.6 (95% CI 2.3–9.5), 6.7 (95% CI 2.9–15.6), and 23.6 (95% CI 10.7–52.4) in women (PNMS-interaction-with-sex = 0.07). Conclusions: The number of NMS was associated with PD in a dose-response manner and the association appeared stronger in men than in women. These findings should be further investigated in population-based prospective studies.