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Significant progress has been made in expanding our understanding of prodromal Parkinson disease (PD), particularly for recognition of early motor and nonmotor signs and symptoms. Although identification of these prodromal features may improve our understanding of the earliest stages of PD, they are individually insufficient for early disease detection and enrollment of participants in prevention trials in most cases because of low sensitivity, specificity, and positive predictive value. Composite cohorts, composed of individuals with multiple co-occurring prodromal features, are an important resource for conducting prodromal PD research and eventual prevention trials because they are more representative of the population at risk for PD, allow investigators to evaluate the efficacy of an intervention across individuals with varying prodromal feature patterns, are able to produce larger sample sizes, and capture individuals at different stages of prodromal PD. A key challenge in identifying individuals with prodromal disease for composite cohorts and prevention trial participation is that we know little about the natural history of prodromal PD. To move toward prevention trials, it is critical that we better understand common prodromal feature patterns and be able to predict the probability of progression and phenoconversion. Ongoing research in cohort studies and administrative databases is beginning to address these questions, but further longitudinal analyses in a large population-based sample are necessary to provide a convincing and definitive strategy for identifying individuals to be enrolled in a prevention trial., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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.)

Objective: To prospectively examine how selected lifestyle factors and family history of Parkinson disease (PD) combine to determine overall PD risk., Methods: We derived risk scores among 69,968 women in the Nurses' Health Study (NHS) (1984-2012) and 45,830 men in the Health Professionals Follow-up Study (HPFS) (1986-2012). Risk scores were computed for each individual based on the following factors previously associated with PD risk: total caffeine intake, smoking, physical activity, and family history of PD for the NHS, and additionally total flavonoid intake and dietary urate index for the HPFS. Hazard ratios were estimated using Cox proportional hazards models. In addition, we performed tests of interactions on both the multiplicative and additive scale between pairs of risk factors., Results: We documented 1,117 incident PD cases during follow-up. The adjusted hazard ratios comparing individuals in the highest category of the reduced risk score to those in the lowest category were 0.33 (95% confidence interval: 0.21, 0.49; p trend < 0.0001) in the NHS and 0.18 (95% confidence interval: 0.10, 0.32; p trend < 0.0001) in the HPFS. Results were similar when applying the risk scores computed by summing the predictors weighted by the log of their individual effect sizes on PD risk in these cohorts. Additive interaction was present between no family history of PD and caffeine in men and between caffeine and physical activity in women., Conclusions: Our results suggest that known protective factors for PD tend to have additive or superadditive effects, so that PD risk is very low in individuals with multiple protective risk factors., (© 2018 American Academy of Neurology.)

Objective: To prospectively examine the association between commonly consumed dairy products and the risk of Parkinson disease (PD) in women and men., Methods: Analyses were based on data from 2 large prospective cohort studies, the Nurses' Health Study (n = 80,736) and the Health Professionals Follow-up Study (n = 48,610), with a total of 26 and 24 years of follow-up, respectively. Both US-based studies were conducted via mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Incident cases of PD (n = 1,036) were identified via questionnaires and subsequently confirmed by reviewing medical records. We also conducted a meta-analysis to combine our study with 3 previously published prospective studies on total milk intake and PD risk and 1 study on total dairy intake and PD risk., Results: While total dairy intake was not significantly associated with PD risk in our cohorts, intake of low-fat dairy foods was associated with PD risk. The pooled, multivariable-adjusted hazard ratio (HR) comparing people who consumed at least 3 servings of low-fat dairy per day to those who consumed none was 1.34 (95% confidence interval [CI] 1.01-1.79, p trend = 0.04). This association appeared to be driven by an increased risk of PD associated with skim and low-fat milk (HR 1.39, 95% CI 1.12-1.73, p trend <0.01). Results were similar in women and men ( p for heterogeneity >0.05). In the meta-analysis, the pooled relative risk comparing extreme categories of total milk intake was 1.56 (95% CI 1.30-1.88), and the association between total dairy and PD became significant (HR 1.27, 95% CI 1.04-1.55)., Conclusions: Frequent consumption of dairy products appears to be associated with a modest increased risk of PD in women and men., (© 2017 American Academy of Neurology.)