open access publication

Article, 2024

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

Neurology, ISSN 1526-632X, 0028-3878, Volume 102, 8, Page e209201, 10.1212/wnl.0000000000209201

Contributors

Zhao, Yujia [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Lai, Y H Lana 0000-0002-1081-0897 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Konijnenberg, Hilde [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Huerta, José Marı'A 0000-0002-9637-3869 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Vinagre-Aragón, Ana 0000-0002-2368-3196 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Sabin, Jara Anna [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Hansen, Johnni 0000-0002-9342-2725 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Petrova, Dafina G 0000-0002-0346-6776 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Sacerdote, Carlotta 0000-0002-8008-5096 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Zamora-Ros, Raul 0000-0002-6236-6804 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Pala, Valeria Maria 0000-0001-5438-970X [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Heath, Alicia K 0000-0001-6517-1300 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Panico, Salvatore 0000-0002-5498-8312 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Guevara, Marcela 0000-0001-9242-6364 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Masala, Giovanna 0000-0002-5758-9069 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Lill, Christina M 0000-0002-2805-1307 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Miller, Gary W [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Peters, Susan M 0000-0001-5662-1971 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Vermeulen, Roel C H 0000-0003-4082-8163 (Corresponding author) [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]

Affiliations

  1. [1] Andalusian School of Public Health
    2. [NORA names: Spain; Europe, EU; OECD];
  2. [2] Biodonostia
    3. [NORA names: Spain; Europe, EU; OECD];
  3. [3] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
    4. [NORA names: Spain; Europe, EU; OECD];
  4. [4] Columbia University
    5. [NORA names: United States; America, North; OECD];
  5. [5] Danish Cancer Society
    6. [NORA names: DCRC Danish Cancer Society Research Center; Non-Profit Organisations; Denmark; Europe, EU; Nordic; OECD];

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

CI, Cox proportional hazards models, European countries, PD incidence, PD onset, PD risk, Parkinson, Parkinson's disease, age, alcohol, alcohol consumption, associated with PD risk, association, association of coffee consumption, background, baseline, blood, blood collection, caffeine, caffeine intake, caffeine metabolites, case-control study, cases, center, coffee, coffee consumption, coffee intake, cohort, collection, conditional logistic regression models, consumption, control, control by age, countries, diagnosis, disease, expert neurologist, fasting status, hazard, hazard ratio, hazards model, high coffee intake, high-resolution mass spectrometry, human studies, incidence, incident PD, incident Parkinson's disease, intake, inverse association, logistic regression models, mass spectrometry, matched controls, medical records, metabolites, model, multivariable-adjusted HR, nested case-control study, neurologists, neuroprotection, nonconsumers, odds, odds ratio, onset, paraxanthine, plasma, plasma caffeine, plasma samples, population-based cohort, primary metabolites, proportional hazards model, quantification, quantify biomarkers, ratio, records, regression models, results, risk, samples, sex, smoking, spectrometry, status, study, study centers, theophylline, years, years before PD onset

Funders

  • Government of Catalonia
  • Danish Cancer Society
  • Institut Gustave Roussy
  • Federal Ministry of Education and Research
  • Swedish Cancer Society
  • Instituto de Salud Carlos III
  • Medical Research Council
  • National Institute for Public Health and the Environment
  • German Cancer Research Center
  • Ministry of Health Welfare and Sport
  • Swedish Research Council
  • National Institute for Health and Care Research
  • Italian Association for Cancer Research
  • German Cancer Aid
  • Cancer Research UK
  • International Agency for Research on Cancer

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