Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population



Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS).


PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment.


Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44–0.90 and OR 0.56; 95% CI 0.38–0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47–0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A).


Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS.

Trial registration

ISRCTN89898870. Registration date: July 24, 2014.

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Fig. 1

Availability of data and materials

There are restrictions on the availability of data for the PREDIMED-Plus trial, due to the signed consent agreements around data sharing, which only allow access to external researchers for studies following the project purposes. Requestors wishing to access the PREDIMED-Plus trial data used in this study can make a request to the PREDIMED-Plus trial Steering Committee chair: The request will then be passed to members of the PREDIMED-Plus Steering Committee for deliberation.


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The authors would especially like to thank the PREDIMED-Plus participants for their enthusiastic collaboration, the PREDIMED-Plus personnel for their outstanding support and staff of all associated primary care centers for their exceptional work. CIBEROBN, CIBERESP and CIBERDEM are initiatives of the Carlos III Health Institute, Spain. We also thank the PREDIMED-Plus Biobank Network, which is part of the National Biobank Platform of the Carlos III Health Institute for storing and managing the biological samples. List of PREDIMED-Plus study investigators: Steering Committee: J. Salas-Salvadó (Coordinator), M.A. Martínez-González, M. Fitó. E. Ros, FJ. Tinahones, D. Corella and R. Estruch. Executive Committee: J. Salas-Salvadó, M.A. Martínez-González, D. Corella, M. Fitó, J. Vioque, D. Romaguera, J.A Martínez, J. Wärnberg, J. Lopez-Miranda, R. Estruch, A. Bueno-Cavanillas, Á.M. Alonso-Gómez, J.A. Tur, FJ. Tinahones, L. Serra-Majem, V. Martin, J. Lapetra, C. Vázquez, X. Pinto, J. Vidal, L. Daimiel, M. Delgado-Rodríguez, M.A. Rubio and E. Ros. Dietary and Lifestyle Intervention Committee: J. Salas-Salvadó (chair), M.A. Martínez-González, M. Fitó and R. Estruch; Dietary Intervention: J. Salas-Salvadó (chair), N. Babio, E. Ros, A. Sánchez-Tainta; Physical Exercise: M. Fitó (chair), H. Schröder, A. Marcos, D. Corella, J. Warnberg; Behavioral support: R. Estruch (chair), F. Fernández-Aranda, C. Botella and J. Salas-Salvadó. Clinical Event Ascertainment Committee: F. Arós (Chair), M. Aldamiz, A. Alonso-Gómez, L. Forga, A. García-Layana, J. Portu, J. Timiraos, A. González-Pinto, I. Zorrilla, M. Martínez-Kareaga, P. Seoane. Chair: Dr. Fernando Arós. Cardiology: Dr. Angel Alonso-Gómez; Dr. Fernando Arós. Neurology: Dr. Juan Timiraos. Internal Medicine: Dr. Mikel Aldamiz; Dr. Joseba Portu. Endocrinology: Dr. Lluis Forga. Ophthalmology: Dr. Alfredo García-Layana. Psychiatry: Dr. Ana González Pinto; Dr. Iñaki Zorrilla. Oncology: Dr. Mireia Martínez; Dr. Patricia Seoane. Independent Data and Safety Monitoring Board: M.J. Stampfer (Harvard School of Public Health), J. Sabate (Loma Linda University), A. Astrup (Copenhagen University), F. Fernandez-Aviles (Universidad Complutense of Madrid), X. Pi-Sunyer (Columbia University). Rovira i Virgili University, Department of Biochemistry and Biotechnology, Human Nutrition Unit, University Hospital of Sant Joan de Reus, Pere Virgili Institute for Health Research, Reus, Spain: R. Pedret Llaberia, R. Gonzalez, R. Sagarra Álamo, F. París Palleja, J. Balsells, J.M. Roca, T. Basora Gallisa, J. Vizcaino, P. Llobet Alpizarte, C. Anguera Perpiñá, M. Llauradó Vernet, C. Caballero, M. Garcia Barco, M.D. Morán Martínez, J. García Rosselló, A. Del Pozo, C. PobletCalaf, P. Arcelin Zabal, X. Floresví, M. Ciutat Benet, A. Palau Galindo, J.J. Cabré Vila, F. Dolz Andrés, M. Soler, M. Gracia Vidal, J. Vilalta J. Boj Casajuana, M. Ricard, F. Saiz, A. Isach, M. Sanchez Marin Martinez, E. Granado Font, C, Lucena Luque, C. 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The PREDIMED-Plus trial was supported by the Spanish government’s official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS) and co-funded by European Union ERDF/ESF, “A way to make Europe”/ “Investing in your future” (five coordinated FIS projects led by JS-S and JVid, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560 and PI19/01332), the Special Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S, the European Research Council (Advanced Research Grant 2013–2018, 340918) to MÁM-G, the Recercaixa Grant to JS-S (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016 and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, and funds from the European Regional Development Fund (CB06/03). This research was also partially funded by EU-H2020 Grant (EAT2BENICE/H2020-SFS-2016–2; Ref 728018). Study resulting from the SLT006/17/00246 grant was funded by the Department of Health of the Generalitat de Catalunya by the call “Acció instrumental de programes de recerca orientats en l'àmbit de la recerca i la innovació en salut.” We thank CERCA Programme/Generalitat de Catalunya for institutional support. This work is partially supported by ICREA under the ICREA Academia program. IP-G receives a grant from the Spanish Ministry of Education, Culture and Sports (FPU 17/01925). L.C.-B. is the recipient of a predoctoral fellowship from the Generalitat de Catalunya's Department of Universities (FI-DGR 2017). NB-T is supported by a postdoctoral fellowship (Juan de la Cierva-Formación, FJC2018-036016-I) MRBL was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER.

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NB and JS-S contributed to study concept and design. IP-G, NB and JS-S performed statistical analyses. IP-G, NB, NB-T, LC-B and JS-S drafted the manuscript. All authors reviewed the manuscript for important intellectual content and approved the final version to be published.

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Correspondence to Nancy Babio or Jordi Salas-Salvadó.

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Conflict of interest

JS-S serves on the board of (and receives grant support through his institution from) the International Nut and Dried Fruit Council and the Eroski Foundation. He also serves on the Executive Committee of the Instituto Danone, Spain, and on the Scientific Committee of the Danone International Institute. He has received research support from the Patrimonio Comunal Olivarero, Spain, and Borges S.A., Spain. He receives consulting fees or travel expenses from Danone, the Eroski Foundation, the Instituto Danone, Spain, and Abbot Laboratories. ER has received research funding through his institution from the California Walnut Commission, Folsom, CA, USA; was a paid member of its Health Research Advisory Group; and is a nonpaid member of its Scientific Advisory Council.

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Not applicable.

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All participants provided their written informed consent. The study protocol and procedures were approved in accordance with the ethical standards of the Declaration of Helsinki.

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A complete list of PREDIMED-Plus investigators is included as an acknowledgements.

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Paz-Graniel, I., Babio, N., Becerra-Tomás, N. et al. Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population. Eur J Nutr (2020).

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  • Cognitive impairment
  • Mini-Mental State Examination
  • Coffee
  • Caffeine
  • PREDIMED-plus