TY - JOUR
T1 - Body Mass Index, Abdominal Adiposity, and Incidence of Parkinson Disease in French Women from the E3N Cohort Study
AU - Portugal, Berta
AU - Artaud, Fanny
AU - Domenighetti, Cloé
AU - Roze, Emmanuel
AU - Degaey, Isabelle
AU - Canonico, Marianne
AU - Elbaz, Alexis
N1 - Funding Information:
This work was realized with the data of the E3N cohort (Inserm) and supported by the Mutuelle Générale de l’Education Nationale (MGEN), the Gustave Roussy Institute, and the French League against Cancer for the constitution and maintenance of the cohort. This work has benefited from State aid managed by the National Research Agency (ANR) under the program “Investment in the future” bearing the reference ANR-10-COHO-0006 and under the program “Young researcher” bearing the reference ANR-18-CE36-0006-01 and a subsidy from the Ministry of Higher Education, Research and Innovation for public service charges bearing the reference No. 2102918823, 2103236497, and 2103586016 and from Iresp (Institut de recherche en santé publique).
Funding Information:
B. Portugal is funded by a doctoral grant from the French Ministry of research; F. Artaud reports no disclosures; C. Domenighetti reports no disclosures; E. Roze received honorarium for speech from Orkyn Aguettant, Elivie and for participating in an advisory board from Allergan and Merz-Pharma, and additionally, he received research support from Merz-Pharma, Orkyn, Aguettant, Elivie, Ipsen, Allergan, Everpharma, Fondation Desmarest, AMADYS, ADCY5.org , Agence Nationale de la Recherche, Societé Française de Médecine Esthétique, and Dystonia Medical Reasearch Foundation; I. Degaey reports no disclosures; M. Canonico has obtained research grants from Agence nationale de la recherché (ANR); A. Elbaz has obtained research grants from the Michael J Fox foundation, Plan Ecophyto (French ministry of agriculture), and France Parkinson. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© American Academy of Neurology.
PY - 2023/1/17
Y1 - 2023/1/17
N2 - Background and ObjectivesPrevious studies on the relationship between body mass index (BMI) and Parkinson disease (PD) provided inconsistent results, likely due to reverse causation explained by weight loss during the prodromal phase. We examined the association of BMI and abdominal adiposity with PD incidence using lagged analyses to address the potential for reverse causation and compared BMI trajectories in patients before diagnosis and matched controls.MethodsWe used data from the E3N cohort study of French women with a 29-year follow-up (1990-2018). BMI (kg/m2) was computed based on self-reported weight and height up to 11 times; up to 6 waist circumference (WC) and hip circumference measures were available. PD diagnoses were validated based on medical records and drug claim databases. Multivariable time-varying Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs according to BMI categories (underweight <18.5 kg/m2; normal = [18.5-25.0[ kg/m2; overweight = [25.0-30.0[ kg/m2; obese ≥30.0 kg/m2). Exposures were lagged by 5 years in main analyses; we used longer lags (10 and 20 years) in sensitivity analyses. We examined trajectories of BMI categories within a nested case-control study using multivariable generalized estimating equations multinomial logistic models.ResultsOf 96,702 women (baseline age = 40-65 years), 1,164 developed PD. PD incidence was lower (HR = 0.76, 95% CI = 0.59-0.98, p = 0.032) among women with obesity compared with those with normal BMI. There was a similar association in analyses using longer lag times (20 years, 598 cases, HR = 0.52, 95% CI = 0.30-0.88, p = 0.016). A similar pattern was seen for WC and waist-height ratio but not waist-hip ratio. Trajectories of BMI categories (1,196 patients and 23,876 controls) showed that obesity was less frequent in patients with PD before diagnosis than in controls, with a statistically significant difference 29 years before. In addition, the frequency of obesity decreased 5-10 years before diagnosis in patients.DiscussionIn this large cohort of women with a long follow-up, obesity was associated with a lower hazard of PD, even when measured 20 years before diagnosis, in agreement with Mendelian randomization studies. Our analyses underscore the importance of lagged analyses to account for reverse causation. These findings warrant further investigations to understand the mechanisms underlying this inverse association.
AB - Background and ObjectivesPrevious studies on the relationship between body mass index (BMI) and Parkinson disease (PD) provided inconsistent results, likely due to reverse causation explained by weight loss during the prodromal phase. We examined the association of BMI and abdominal adiposity with PD incidence using lagged analyses to address the potential for reverse causation and compared BMI trajectories in patients before diagnosis and matched controls.MethodsWe used data from the E3N cohort study of French women with a 29-year follow-up (1990-2018). BMI (kg/m2) was computed based on self-reported weight and height up to 11 times; up to 6 waist circumference (WC) and hip circumference measures were available. PD diagnoses were validated based on medical records and drug claim databases. Multivariable time-varying Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs according to BMI categories (underweight <18.5 kg/m2; normal = [18.5-25.0[ kg/m2; overweight = [25.0-30.0[ kg/m2; obese ≥30.0 kg/m2). Exposures were lagged by 5 years in main analyses; we used longer lags (10 and 20 years) in sensitivity analyses. We examined trajectories of BMI categories within a nested case-control study using multivariable generalized estimating equations multinomial logistic models.ResultsOf 96,702 women (baseline age = 40-65 years), 1,164 developed PD. PD incidence was lower (HR = 0.76, 95% CI = 0.59-0.98, p = 0.032) among women with obesity compared with those with normal BMI. There was a similar association in analyses using longer lag times (20 years, 598 cases, HR = 0.52, 95% CI = 0.30-0.88, p = 0.016). A similar pattern was seen for WC and waist-height ratio but not waist-hip ratio. Trajectories of BMI categories (1,196 patients and 23,876 controls) showed that obesity was less frequent in patients with PD before diagnosis than in controls, with a statistically significant difference 29 years before. In addition, the frequency of obesity decreased 5-10 years before diagnosis in patients.DiscussionIn this large cohort of women with a long follow-up, obesity was associated with a lower hazard of PD, even when measured 20 years before diagnosis, in agreement with Mendelian randomization studies. Our analyses underscore the importance of lagged analyses to account for reverse causation. These findings warrant further investigations to understand the mechanisms underlying this inverse association.
UR - http://www.scopus.com/inward/record.url?scp=85146365250&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/36192171
U2 - 10.1212/WNL.0000000000201468
DO - 10.1212/WNL.0000000000201468
M3 - Article
C2 - 36192171
AN - SCOPUS:85146365250
SN - 0028-3878
VL - 100
SP - E324-E335
JO - Neurology
JF - Neurology
IS - 3
ER -