Known protective factors for Parkinson disease (PD) tend to have additive or superadditive effects, such that the combination of known lifestyle factors and family history can explain 80% of cases of the disease in men and 63% of cases in women, according to the results of an analysis of risk scores from the Health Professionals Follow-up Study and Nurses’ Health Study that were published in Neurology.

Risk factors for all study participants were calculated on the basis of the following factors known to be previously linked to PD risk: total caffeine intake, smoking, physical activity, and family history of PD for those from the Nurses’ Health Study, along with flavonoid intake and dietary urate index for those from the Health Professionals Follow-up Study. Hazard ratios (HRs) were estimated via use of Cox proportional hazards models.

During follow-up, a total of 1117 incident cases of PD were documented. Adjusted HRs that compared persons in the highest category of the reduced risk score with those in the lowest category were 0.33 (95% CI, 0.21-0.49; Ptrend <.0001) in the Nurses’ Health Study and 0.18 (95% CI, 0.10-0.32; Ptrend <.0001) in the Health Professionals Follow-up Study, both of which were statistically significant.

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Results were similar when applying the risk scores calculated by adding the predictors weighted by the log of their individual effect sizes on PD risk in these patient cohorts. In men, additive interaction was present between no family history of PD and caffeine; in women, additive interaction was demonstrated between caffeine and physical activity.

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The investigators concluded that the results of this study show that PD risk is very low among individuals with multiple protective risk factors, thus supporting the protective synergism between caffeine intake and physical activity in women, and between caffeine intake and family history of PD in men.


Kim IY, O’Reilly ÉJ, Hughes KC, et al. Integration of risk factors for Parkinson disease in 2 large longitudinal cohorts [published online April 11, 2018]. Neurology. doi: 10.1212/WNL.0000000000005473