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Objective: To assess the relationship between diet pattern and prodromal Parkinson disease (PD) features., Methods: These analyses include 47,679 participants from the Nurses' Health Study and the Health Professionals Follow-up Study. Since 1986, both cohorts have collected dietary information every 4 years and calculated scores for adherence to different diet patterns, including the alternate Mediterranean diet (aMED) and the Alternative Healthy Eating Index (AHEI). In 2012, participants responded to questions regarding constipation and probable REM sleep behavior disorder. For a subset of 17,400 respondents to the 2012 questionnaire, 5 additional prodromal features of PD were assessed in 2014 to 2015. We used multinomial logistic regression to estimate the association between baseline (1986) diet pattern score quintiles and number of prodromal features (0, 1, 2, or ≥3) in 2012 to 2015. Additional analyses investigated the association between long-term adherence to these dietary patterns over 20 years and prodromal features suggestive of PD., Results: In a comparison of extreme aMED diet quintiles, the odds ratio for ≥3 vs 0 features was 0.82 (95% confidence interval [CI] 0.68-1.00, false discovery rate [FDR]-adjusted p trend = 0.03) at baseline and 0.67 (95% CI 0.54-0.83, FDR- p trend < 0.001) for long-term diet; results were equally strong for the association with AHEI scores. Higher adherence to these diets was inversely associated with individual features, including constipation, excessive daytime sleepiness, and depression., Conclusions: The inverse association between these diet patterns and prodromal PD features is consistent with previous findings and suggests that adherence to a healthy diet may reduce the occurrence of nonmotor symptoms that often precede PD diagnosis., (© 2020 American Academy of Neurology.)

Objective: To investigate the relationship between physical activity and prodromal features of Parkinson disease that often precede the clinical diagnosis., Methods: Included are participants in 2 well-established cohorts: the Nurses' Health Study and the Health Professionals Follow-up Study. Physical activity was assessed using validated questionnaires at baseline (1986) and every 2 years until 2008. Prodromal features (e.g., constipation, hyposmia, and probable REM sleep behavior disorder [pRBD]) were assessed in 2012-2014., Results: The multivariable-adjusted odds ratio (OR) for having ≥3 prodromal features vs none comparing the highest to the lowest quintile were 0.65 (95% confidence interval [CI] 0.53-0.79; p trend = 0.0006) for baseline physical activity and 0.52 (95% CI 0.35-0.76; p trend = 0.009) for cumulative average physical activity. Considering each feature independently, baseline physical activity was associated with lower odds of constipation (OR 0.78, 95% CI 0.73-0.83; p trend < 0.0001), excessive daytime sleepiness (OR 0.72, 95% CI 0.60-0.86; p trend = 0.002), depressive symptoms (OR 0.82, 95% CI 0.69-0.97; p trend = 0.13), and bodily pain (OR 0.81, 95% CI 0.68-0.96; p trend = 0.03). Similar or stronger associations were observed for cumulative average physical activity, which, in addition, was associated with pRBD (OR 0.85, 95% CI 0.77-0.95; p trend = 0.02). In contrast, neither hyposmia nor impaired color vision was associated with physical activity. Early life physical activity was associated with constipation and, in men only, with the co-occurrence of ≥3 features., Conclusions: The reduced prevalence of prodromal features associated with Parkinson disease in older individuals who were more physically active in midlife and beyond is consistent with the hypothesis that high levels of physical activity may reduce risk of Parkinson disease., (© 2019 American Academy of Neurology.)

Background: Several non-motor features may individually contribute to identify prodromal Parkinson's disease (PD), but little is known on how they interact., Methods: We conducted a case-control study nested within the Health Professionals Follow-up Study in a large cohort of men age 40-75 at recruitment in 1986. Cases (n=120) had confirmed PD, were<85 in January 2012, returned a 2012 questionnaire with questions on probable rapid eye movement sleep behaviour disorder (RBD) and constipation sent to all cohort participants and completed in 2014 the Brief Smell Identification Test and a questionnaire assessing parkinsonism and other non-motor PD features (including depressive symptoms, excessive daytime sleepiness, impaired colour vision and body pain). Controls (n=6479) met the same criteria as cases, except for the PD diagnosis., Results: Concurrent constipation, probable RBD and hyposmia were present in 29.3% of cases and 1.1% of controls, yielding an age-adjusted OR of 160(95%CI 72.8to353) for three features versus none. The odds of PD increased exponentially with additional non-motor features (OR for 6-7 features versus none: 1325; 95%CI333to5279). Among men without PD, the number of non-motor features was associated with odds of parkinsonism (OR for 6-7 features versus none: 89; 95%CI21.2to375). We estimated that in a population with a prodromal PD prevalence of 2%, concurrent constipation, probable RBD and hyposmia would have a maximum sensitivity of 29% and a positive predictive value (PPV) of 35%. The PPV could increase up to 70% by including additional features, but with sharply decreased sensitivity., Conclusions: Concurrent constipation, probable RBD and hyposmia are strongly associated with PD. Because these features often precede motor symptoms and their co-occurrence could provide an efficient method for early PD identification., Competing Interests: Competing interest: XG has served on committees of the Sleep Research Society, American Academy of Sleep Medicine, and Parkinson Study Group and received funding from the NIH/NINDS. MAS served on the scientific advisory board for CBD Solutions (foundation), has served as a consultant for New Beta Innovation (company) and Harvard University and is funded by NIH grants NS090259, NS098746, U13NS103523, Department of Defense W81XWH-11-1-0150, the Michael J. Fox Foundation, the Parkinson’s Alliance, the Parkinson’s Foundation and Target ALS Foundation. AA received a research grant from the Department of Defense related to this work. He has also received research grants from the National Institutes of Health, the Michael J. Fox Foundation and the National Multiple Sclerosis Society, outside of this work., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)