Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort

Yujia Zhao; Anushree Ray; Karin Broberg; Maria Kippler; Christina M Lill; Paolo Vineis; Verena A Katzke; Miguel Rodriguez-Barranco; María-Dolores Chirlaque; Marcela Guevara; Jesús-Humberto Gómez; Johnni Hansen; Salvatore Panico; Lefkos T Middleton; Giovanna Masala; Valeria Pala; Ana Vinagre-Aragon; Maurizio Zibetti; Roel Vermeulen; Susan Peters

doi:10.1002/mds.29602

Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort

Yujia Zhao, Anushree Ray, Karin Broberg, Maria Kippler, Christina M Lill, Paolo Vineis, Verena A Katzke, Miguel Rodriguez-Barranco, María-Dolores Chirlaque, Marcela Guevara, Jesús-Humberto Gómez, Johnni Hansen, Salvatore Panico, Lefkos T Middleton, Giovanna Masala, Valeria Pala, Ana Vinagre-Aragon, Maurizio Zibetti, Roel Vermeulen, Susan Peters^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality. Objective: The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk. Methods: A case-control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis. Results: Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95% confidence interval] for the highest quartile, 0.70 [0.42–1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01–0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45–7.93]). Conclusions: We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco-derived metals.

Original language	English
Pages (from-to)	2302-2307
Number of pages	6
Journal	Movement Disorders
Volume	38
Issue number	12
Early online date	7 Sept 2023
DOIs	https://doi.org/10.1002/mds.29602
Publication status	Published - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Funding

This work was supported by Stichting ParkinsonFonds. Y.Z. received support from the China Scholarship Council during the PhD period in Utrecht University‐Institute for Risk Assessment Sciences. C.M.L. was supported by the Heisenberg program of the German Research Foundation (grant LI 2654/4‐1) and by The Michael J. Fox Foundation (grant MJFF‐008994). The national cohorts were supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam‐Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), National Institute for Public Health and the Environment (RIVM), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Health Research Fund (FIS) – Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, the Catalan Institute of Oncology—ICO, CERCA Program/Generalitat de Catalunya for the institutional support to IDIBELL (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC‐Norfolk; C8221/A29017 to EPIC‐Oxford), Medical Research Council (MR/N003284/1, MC‐UU_12015/1, and MC_UU_00006/1 to EPIC‐Norfolk; MR/M012190/1 to EPIC‐Oxford), University of Cambridge (United Kingdom). We thank Michael Levi, Institute of Environmental Medicine, Karolinska Institutet, Sweden, for the measurement of metals in erythrocytes. The coordination of EPIC was financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre. We are grateful to all the participants who have been part of the project. This work was supported by Stichting ParkinsonFonds. Y.Z. received support from the China Scholarship Council during the PhD period in Utrecht University-Institute for Risk Assessment Sciences. C.M.L. was supported by the Heisenberg program of the German Research Foundation (grant LI 2654/4-1) and by The Michael J. Fox Foundation (grant MJFF-008994). The national cohorts were supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), National Institute for Public Health and the Environment (RIVM), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Health Research Fund (FIS) – Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, the Catalan Institute of Oncology—ICO, CERCA Program/Generalitat de Catalunya for the institutional support to IDIBELL (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/N003284/1, MC-UU_12015/1, and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford), University of Cambridge (United Kingdom). We thank Michael Levi, Institute of Environmental Medicine, Karolinska Institutet, Sweden, for the measurement of metals in erythrocytes. The coordination of EPIC was financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre. We are grateful to all the participants who have been part of the project.

Funders	Funder number
Associazione Italiana per la Ricerca
Catalan Institute of Oncology
Compagnia di SanPaolo
County Councils of Skåne
Dutch Prevention Funds
Dutch ZON (Zorg Onderzoek Nederland
German Institute of Human Nutrition Potsdam-Rehbruecke
German Institute of Human Nutrition Potsdam‐Rehbruecke
Health Research Fund
LK Research Funds
NKR
National Institute for Public Health and the Environment
Netherlands Cancer Registry
de Catalunya
Michael J. Fox Foundation for Parkinson's Research	MJFF‐008994
Kræftens Bekæmpelse
Deutsches Krebsforschungszentrum
Centre International de Recherche sur le Cancer
National Research Council
University of Maryland School of Public Health
Department of Epidemiology and Biostatistics, University of California, San Francisco
School of Public Health
Medical Research Council	MC‐UU_12015/1, MR/M012190/1, MR/N003284/1, MC_UU_00006/1
Cancer Research UK	C8221/A29017, C864/A14136
World Cancer Research Fund
University of Cambridge
Imperial College London
Deutsche Forschungsgemeinschaft	LI 2654/4‐1
Institut national de la santé et de la recherche médicale
Bundesministerium für Bildung und Forschung
Cancerfonden
Ministerie van Volksgezondheid, Welzijn en Sport
Karolinska Institutet
Ligue Contre le Cancer
Vetenskapsrådet
China Scholarship Council
Instituto de Salud Carlos III
Associazione Italiana per la Ricerca sul Cancro
Deutsche Krebshilfe
Rijksinstituut voor Volksgezondheid en Milieu
Institut Gustave-Roussy
Mutuelle Générale de l'Education Nationale
Stichting ParkinsonFonds
Consejería de Salud y Familias, Junta de Andalucía
NIHR Imperial Biomedical Research Centre

Keywords

Parkinson's disease
metals
prospective exposure assessment
cohort study

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10.1002/mds.29602Licence: CC BY-NC-ND

Movement Disorders - 2023 - Zhao - Prediagnostic Blood Metal Levels and the Risk of Parkinson s Disease A Large EuropeanFinal published version, 299 KBLicence: CC BY-NC-ND

Cite this

Zhao, Y., Ray, A., Broberg, K., Kippler, M., Lill, C. M., Vineis, P., Katzke, V. A., Rodriguez-Barranco, M., Chirlaque, M.-D., Guevara, M., Gómez, J.-H., Hansen, J., Panico, S., Middleton, L. T., Masala, G., Pala, V., Vinagre-Aragon, A., Zibetti, M., Vermeulen, R., & Peters, S. (2023). Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort. Movement Disorders, 38(12), 2302-2307. https://doi.org/10.1002/mds.29602

@article{8ac3d4fa987443b1bffe94605b658f0f,

title = "Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort",

abstract = "Background: Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality. Objective: The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk. Methods: A case-control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis. Results: Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95\% confidence interval] for the highest quartile, 0.70 [0.42–1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01–0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45–7.93]). Conclusions: We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco-derived metals.",

keywords = "Parkinson's disease, metals, prospective exposure assessment, cohort study",

author = "Yujia Zhao and Anushree Ray and Karin Broberg and Maria Kippler and Lill, \{Christina M\} and Paolo Vineis and Katzke, \{Verena A\} and Miguel Rodriguez-Barranco and Mar{\'i}a-Dolores Chirlaque and Marcela Guevara and Jes{\'u}s-Humberto G{\'o}mez and Johnni Hansen and Salvatore Panico and Middleton, \{Lefkos T\} and Giovanna Masala and Valeria Pala and Ana Vinagre-Aragon and Maurizio Zibetti and Roel Vermeulen and Susan Peters",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2023",

month = dec,

doi = "10.1002/mds.29602",

language = "English",

volume = "38",

pages = "2302--2307",

journal = "Movement Disorders",

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Zhao, Y, Ray, A, Broberg, K, Kippler, M, Lill, CM, Vineis, P, Katzke, VA, Rodriguez-Barranco, M, Chirlaque, M-D, Guevara, M, Gómez, J-H, Hansen, J, Panico, S, Middleton, LT, Masala, G, Pala, V, Vinagre-Aragon, A, Zibetti, M, Vermeulen, R & Peters, S 2023, 'Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort', Movement Disorders, vol. 38, no. 12, pp. 2302-2307. https://doi.org/10.1002/mds.29602

TY - JOUR

T1 - Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease

T2 - A Large European Prospective Cohort

AU - Zhao, Yujia

AU - Ray, Anushree

AU - Broberg, Karin

AU - Kippler, Maria

AU - Lill, Christina M

AU - Vineis, Paolo

AU - Katzke, Verena A

AU - Rodriguez-Barranco, Miguel

AU - Chirlaque, María-Dolores

AU - Guevara, Marcela

AU - Gómez, Jesús-Humberto

AU - Hansen, Johnni

AU - Panico, Salvatore

AU - Middleton, Lefkos T

AU - Masala, Giovanna

AU - Pala, Valeria

AU - Vinagre-Aragon, Ana

AU - Zibetti, Maurizio

AU - Vermeulen, Roel

AU - Peters, Susan

PY - 2023/12

Y1 - 2023/12

N2 - Background: Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality. Objective: The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk. Methods: A case-control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis. Results: Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95% confidence interval] for the highest quartile, 0.70 [0.42–1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01–0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45–7.93]). Conclusions: We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco-derived metals.

AB - Background: Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality. Objective: The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk. Methods: A case-control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis. Results: Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95% confidence interval] for the highest quartile, 0.70 [0.42–1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01–0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45–7.93]). Conclusions: We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco-derived metals.

KW - Parkinson's disease

KW - metals

KW - prospective exposure assessment

KW - cohort study

UR - https://www.scopus.com/pages/publications/85170553703

U2 - 10.1002/mds.29602

DO - 10.1002/mds.29602

M3 - Article

C2 - 37675653

SN - 0885-3185

VL - 38

SP - 2302

EP - 2307

JO - Movement Disorders

JF - Movement Disorders

IS - 12

ER -

Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort

Abstract

Bibliographical note

Funding

Keywords

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