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@ARTICLE{Zhao:289134,
      author       = {Y. Zhao and Y. Lai and H. Konijnenberg and J. M. Huerta and
                      A. Vinagre-Aragon and J. A. Sabin$^*$ and J. Hansen and D.
                      Petrova and C. Sacerdote and R. Zamora-Ros and V. Pala and
                      A. K. Heath and S. Panico and M. Guevara and G. Masala and
                      C. M. Lill and G. W. Miller and S. Peters and R. Vermeulen},
      title        = {{A}ssociation of {C}offee {C}onsumption and {P}rediagnostic
                      {C}affeine {M}etabolites {W}ith {I}ncident {P}arkinson
                      {D}isease in a {P}opulation-{B}ased {C}ohort.},
      journal      = {Neurology},
      volume       = {102},
      number       = {8},
      issn         = {0028-3878},
      address      = {[Erscheinungsort nicht ermittelbar]},
      publisher    = {Ovid},
      reportid     = {DKFZ-2024-00601},
      pages        = {e209201},
      year         = {2024},
      abstract     = {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.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.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.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     = {Humans / Caffeine: metabolism / Coffee / Parkinson Disease:
                      diagnosis / Parkinson Disease: epidemiology / Parkinson
                      Disease: etiology / Case-Control Studies / Prospective
                      Studies / Risk Factors / Caffeine (NLM Chemicals) / Coffee
                      (NLM Chemicals)},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38513162},
      doi          = {10.1212/WNL.0000000000209201},
      url          = {https://inrepo02.dkfz.de/record/289134},
}