Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort

Yujia Zhao; Yunjia Lai; Hilde Konijnenberg; José María Huerta; Ana Vinagre-Aragon; Jara Anna Sabin; Johnni Hansen; Dafina Petrova; Carlotta Sacerdote; Raul Zamora-Ros; Valeria Pala; Alicia K Heath; Salvatore Panico; Marcela Guevara; Giovanna Masala; Christina M Lill; Gary W Miller; Susan Peters; Roel Vermeulen

doi:10.1212/WNL.0000000000209201

Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort

Yujia Zhao, Yunjia Lai, Hilde Konijnenberg, José María Huerta, Ana Vinagre-Aragon, Jara Anna Sabin, Johnni Hansen, Dafina Petrova, Carlotta Sacerdote, Raul Zamora-Ros, Valeria Pala, Alicia K Heath, Salvatore Panico, Marcela Guevara, Giovanna Masala, Christina M Lill, Gary W Miller, Susan Peters, Roel Vermeulen

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

Abstract

BACKGROUND AND OBJECTIVES: Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD.

METHODS: Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk.

RESULTS: In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results.

DISCUSSION: This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.

Original language	English
Article number	e209201
Pages (from-to)	1-12
Number of pages	12
Journal	Neurology
Volume	102
Issue number	8
DOIs	https://doi.org/10.1212/WNL.0000000000209201
Publication status	Published - 23 Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s).

Funding

The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and 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 (BRC). The authors thank all the participants who have been part of the project. The authors also thank Lars Forsgren from EPIC-Umea for reviewing the manuscript. The national cohorts are funded by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, and Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DifE), and 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), and Statistics Netherlands (The Netherlands); Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and 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 Skane and Vasterbotten (Sweden); and 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).

Funders	Funder number
International Agency for Research on Cancer (IARC)
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London	C864/A14136
NIHR Imperial Biomedical Research Centre (BRC) - Danish Cancer Society (Denmark)
Ligue Contre le Cancer	C8221/A29017
Institut Gustave Roussy	MR/N003284/1
German Cancer Aid

Keywords

Caffeine/metabolism
Case-Control Studies
Coffee
Humans
Parkinson Disease/diagnosis
Prospective Studies
Risk Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1212/WNL.0000000000209201Licence: CC BY

WNL.0000000000209201Final published version, 280 KBLicence: CC BY

Cite this

Zhao, Y., Lai, Y., Konijnenberg, H., Huerta, J. M., Vinagre-Aragon, A., Sabin, J. A., Hansen, J., Petrova, D., Sacerdote, C., Zamora-Ros, R., Pala, V., Heath, A. K., Panico, S., Guevara, M., Masala, G., Lill, C. M., Miller, G. W., Peters, S., & Vermeulen, R. (2024). Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort. Neurology, 102(8), 1-12. Article e209201. https://doi.org/10.1212/WNL.0000000000209201

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title = "Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort",

abstract = "BACKGROUND AND OBJECTIVES: Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD.METHODS: Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk.RESULTS: In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results. DISCUSSION: This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.",

keywords = "Caffeine/metabolism, Case-Control Studies, Coffee, Humans, Parkinson Disease/diagnosis, Prospective Studies, Risk Factors",

author = "Yujia Zhao and Yunjia Lai and Hilde Konijnenberg and Huerta, {Jos{\'e} Mar{\'i}a} and Ana Vinagre-Aragon and Sabin, {Jara Anna} and Johnni Hansen and Dafina Petrova and Carlotta Sacerdote and Raul Zamora-Ros and Valeria Pala and Heath, {Alicia K} and Salvatore Panico and Marcela Guevara and Giovanna Masala and Lill, {Christina M} and Miller, {Gary W} and Susan Peters and Roel Vermeulen",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s).",

year = "2024",

month = apr,

day = "23",

doi = "10.1212/WNL.0000000000209201",

language = "English",

volume = "102",

pages = "1--12",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "8",

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Zhao, Y, Lai, Y, Konijnenberg, H, Huerta, JM, Vinagre-Aragon, A, Sabin, JA, Hansen, J, Petrova, D, Sacerdote, C, Zamora-Ros, R, Pala, V, Heath, AK, Panico, S, Guevara, M, Masala, G, Lill, CM, Miller, GW, Peters, S & Vermeulen, R 2024, 'Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort', Neurology, vol. 102, no. 8, e209201, pp. 1-12. https://doi.org/10.1212/WNL.0000000000209201

TY - JOUR

T1 - Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort

AU - Zhao, Yujia

AU - Lai, Yunjia

AU - Konijnenberg, Hilde

AU - Huerta, José María

AU - Vinagre-Aragon, Ana

AU - Sabin, Jara Anna

AU - Hansen, Johnni

AU - Petrova, Dafina

AU - Sacerdote, Carlotta

AU - Zamora-Ros, Raul

AU - Pala, Valeria

AU - Heath, Alicia K

AU - Panico, Salvatore

AU - Guevara, Marcela

AU - Masala, Giovanna

AU - Lill, Christina M

AU - Miller, Gary W

AU - Peters, Susan

AU - Vermeulen, Roel

PY - 2024/4/23

Y1 - 2024/4/23

N2 - BACKGROUND AND OBJECTIVES: Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD.METHODS: Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk.RESULTS: In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results. DISCUSSION: This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.

AB - BACKGROUND AND OBJECTIVES: Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD.METHODS: Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk.RESULTS: In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results. DISCUSSION: This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.

KW - Caffeine/metabolism

KW - Case-Control Studies

KW - Coffee

KW - Humans

KW - Parkinson Disease/diagnosis

KW - Prospective Studies

KW - Risk Factors

U2 - 10.1212/WNL.0000000000209201

DO - 10.1212/WNL.0000000000209201

M3 - Article

C2 - 38513162

SN - 0028-3878

VL - 102

SP - 1

EP - 12

JO - Neurology

JF - Neurology

IS - 8

M1 - e209201

ER -

Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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