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.