Objective: We examined the association between BMI and PD incidence in women from the E3N cohort with repeated BMI measures over 29 years of follow-up, and used lagged analyses to address reverse causation.

Background: The relationship between body mass index (BMI) and Parkinson’s disease (PD) is complex and may be affected by reverse causation due to weight loss in the years preceding PD onset [1]. A meta-analysis of 10 cohort studies showed no association, but there was large heterogeneity [2]. In addition, a recent Mendelian randomization (MR) study showed that higher BMI was associated with lower PD risk, thus in favor of a causal association [3].

Method: We followed 95,612 women between 1990-2018 through biennial self-administered questionnaires on lifestyle and medical history (including PD). Incident PD cases were ascertained through a multistep process, and their medical records were examined by an expert panel in order to validate diagnoses; in case of insufficient data, we used a validated PD algorithm based on drug claims databases (available since 2004) [4]. We computed BMI as weight divided by height squared (kg/m²). Time dependent Cox proportional hazards models with age as the time scale were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Exposures were lagged by 5 years to account for reverse causation, and by 10 years in sensitivity analyses. Analyses were adjusted for physical activity, smoking, parity, rural living and menopause.

Results: Over the follow-up, 1,216 women developed PD (mean follow-up= 26.7 years). PD incidence decreased with increasing BMI (p-trend=0.0273). Compared to women with normal BMI (18.5-24.9 kg/m²), PD incidence was lower in overweight (25.0-29.9 kg/m²; HR=0.88, 95%CI=0.76-1.00) and obese women (≥30.0 kg/m²; HR=0.81, 95%CI= 0.64-1.03). Analyses lagged by 10 years yielded consistent findings.

Conclusion: Our findings support recent MR results and suggest that women who are overweight or obese have a lower PD incidence than those in the normal BMI group, and that this inverse association is not explained by reverse causation. The mechanisms underlying this apparent protective effect warrants further study.

References: 1. Ma K, Xiong N, Shen Y, Han C, Liu L, Zhang G, et al. Weight Loss and Malnutrition in Patients with Parkinson’s Disease: Current Knowledge and Future Prospects. Front Aging Neurosci. 2018;10:1. 2. Wang YL, Wang YT, Li JF, Zhang YZ, Yin HL, Han B. Body Mass Index and Risk of Parkinson’s Disease: A Dose-Response Meta-Analysis of Prospective Studies. PLoS One. 2015;10(6):e0131778. 3. Noyce AJ, Kia DA, Hemani G, Nicolas A, Price TR, De Pablo-Fernandez E, et al. Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study. PLoS Med. 2017;14(6):e1002314. 4. Moisan F, Gourlet V, Mazurie J-L, Dupupet J-L, Houssinot J, Goldberg M, et al. Prediction Model of Parkinson’s Disease Based on Antiparkinsonian Drug Claims. American Journal of Epidemiology. 2011;174(3):354-63.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/body-mass-index-and-incidence-of-parkinsons-disease-in-french-women-from-the-e3n-cohort-study/