Objective: To derive a risk score for Parkinson’s disease (PD) based on lifestyle factors and family history and assess potential multiplicative and additive interaction between predictors of PD.

Background: Numerous lifestyle factors have been related to risk of PD, but little is known on how these factors interact with each other. We sought to determine the overall combined effect of several known predictors of PD using risk scores in two large, prospective cohorts.

Methods: We developed and applied risk scores among 90,638 women in the Nurses’ Health Study (NHS) (1984-2012) and 44,815 men in the Health Professionals Follow-up Study (HPFS) (1986-2012). We computed the risk score 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. We assigned one point per increase in quintile for each factor, with the exception of family history, for which we assigned a score of 5 for absence and 0 for presence of family history. The scores were summed to compute the overall score (NHS: 3-20; HPFS: 5-30). We estimated hazard ratios (HRs) using Cox proportional hazards models. Effect modification on the multiplicative scale was assessed by testing significance of the statistical interaction terms in the Cox model and additive interaction was assessed by computing the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (SI).

Results: We observed 456 PD cases in NHS and 591 PD cases in HPFS during follow up. The adjusted HRs comparing the highest of the five categories of the risk score to the lowest category of the risk score was 0.28 (95% CI: 0.18, 0.43; p_trend <0.0001) in the NHS and 0.18 (95% CI: 0.10, 0.34; 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, possibly suggesting a synergic protective effect, was present between no family history of PD and caffeine intake in both the NHS and HPFS and caffeine and physical activity in NHS.

Conclusions: Our results suggest that known protective factors for PD have additive or super-additive effects, so that PD risk is very low in individuals with multiple protective risk factors.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/integration-of-risk-factors-for-pd-in-two-large-longitudinal-cohorts/