Virgin olive oil supplementation and long-term cognition: the Predimed-Navarra randomized, trial

Abstract

Objective

XXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet).

Design

XXXrandomized trial after 6.5 years of nutritional intervention.

Setting

Eight primary care centers affiliated to the University of Navarra.

Participants

A random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1± 5.7 years at cognitive evaluation).

Interventions

Nutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil [EVOO] or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter.

Measurements

XXXcognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment [MCI] or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention.

Results

Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. After adjustment for sex, age, education, apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, this group also showed lower MCI (OR=0.34 95% CI: 0.12–0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls.

Conclusion

A long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.

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References

  1. 1.

    Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V, Covas MI, Fiol M, Gómez-Gracia E, López-Sabater MC, Vinyoles E, Arós F, Conde M, Lahoz C, Lapetra J, Sáez G, Ros E; PREDIMED Study Investigators (2006) Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 145:1–11.

    PubMed  Article  Google Scholar 

  2. 2.

    Trichopoulou A, Bamia C, Trichopoulos D (2009) Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study. BMJ. 338:b2337.doi: 10.1136/bmj.b2337.

    PubMed  Article  Google Scholar 

  3. 3.

    Martínez-González MA, García-López M, Bes-Rastrollo M, Toledo E, Martínez-Lapiscina EH, Delgado-Rodriguez M, Vazquez Z, Benito S, Beunza JJ (2011) Mediterranean diet and the incidence of cardiovascular disease: A Spanish cohort. NutrMetabCardiovasc Dis 21:237–244.doi: 10.1016/j.numecd.2009.10.005.

    Google Scholar 

  4. 4.

    Sofi F, Abbate R, Gensini GF, Casini A (2010) Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J ClinNutr 92:1189–1196.doi: 10.3945/ajcn.2010.29673.

    Article  CAS  Google Scholar 

  5. 5.

    Benetou V, Trichopoulou A, Orfanos P, Naska A, Lagiou P, Boffetta P, Trichopoulos D; Greek EPIC cohort (2008) Conformity to traditional Mediterranean diet and cancer incidence: the Greek EPIC cohort. Br J Cancer 99:191–195.doi: 10.1038/sj.bjc.6604418.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Trichopoulou A, Costacou T, Bamia C, Trichopoulous D (2003) Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 348:2599–2608.

    PubMed  Article  Google Scholar 

  7. 7.

    Scarmeas N, Luchsinger JA, Mayeux R, Schupf N, Stern Y (2008) Mediterranean diet and mortality in a US population. Arch Intern Med 168:1823–1824.doi: 10.1001/archinte.168.16.1823.

    PubMed  Article  Google Scholar 

  8. 8.

    Mecocci P (2004) Oxidative stress in mild cognitive impairment and Alzheimer disease: a continuum. J Alzheimers Dis 6:159–163.

    PubMed  CAS  Google Scholar 

  9. 9.

    Galimberti D, Scarpini E (2011) Inflammation and oxidative damage in Alzheimer’s disease: friend or foe? Front Biosci (Schol Ed) 3:252–266.

    Article  Google Scholar 

  10. 10.

    Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R (2005) Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology 65:545–551.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Martínez-González MÁ, Corella D, Salas-Salvadó J, Ros E, Covas MI, Fiol M, Wärnberg J, Arós F, Ruíz-Gutiérrez V, Lamuela-Raventós RM, Lapetra J, Muñoz MÁ, Martínez JA, Sáez G, Serra-Majem L, Pintó X, Mitjavila MT, Tur JA, Portillo MP, Estruch R; PREDIMED Study Investigators (2012) Cohort profile: design and methods of the PREDIMED study. Int J Epidemiol 41:377–385. doi: 10.1093/ije/dyq250.

    PubMed  Article  Google Scholar 

  12. 12.

    Salas-Salvadó J, Garcia-Arellano A, Estruch R, Marquez-Sandoval F, Corella D, Fiol M, Gómez-Gracia E, Viñoles E, Arós F, Herrera C, Lahoz C, Lapetra J, Perona JS, Muñoz-Aguado D, Martínez-González MA, Ros E; PREDIMED Investigators (2008) Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease. Eur J ClinNutr 62:651–659.

    Article  Google Scholar 

  13. 13.

    Psaltopoulou T, Kyrozis A, Stathopoulos P, Trichopoulos D, Vassilopoulos D, Trichopoulou A (2008) Diet, physical activity and cognitive impairment among elders: the EPIC-Greece cohort (European Prospective Investigation into Cancer and Nutrition). Public Health Nutr 11:1054–1062. doi:10.1017/S1368980007001607.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Féart C, Samieri C, Rondeau V, Amieva H, Portet F, Dartigues JF, Scarmeas N, Barberger-Gateau P (2009) Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. JAMA 302:638–648.doi: 10.1001/jama.2009.1146.

    PubMed  Article  Google Scholar 

  15. 15.

    Kesse-Guyot E, Andreeva VA, Lassale C, Ferry M, Jeandel C, Hercberg S, Galan P; the SU.VI.MAX 2 Research Group (2013). Mediterranean diet and cognitive function: a French study. Am J Clin Nutr 2013 [Epub ahead of print]

    Google Scholar 

  16. 16.

    Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA (2006) Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 59:912–921.

    PubMed  Article  Google Scholar 

  17. 17.

    Tangney CC, Kwasny MJ, Li H, Wilson RS, Evans DA, Morris MC (2011) Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am J ClinNutr 93:601–607. doi: 10.3945/ajcn.110.007369

    Article  CAS  Google Scholar 

  18. 18.

    Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA (2009) Mediterranean diet and mild cognitive impairment. Arch Neurol 66:216–225.doi: 10.1001/archneurol.2008.536.

    PubMed  Article  Google Scholar 

  19. 19.

    Roberts RO, Geda YE, Cerhan JR, Knopman DS, Cha RH, Christianson TJ, Pankratz VS, Ivnik RJ, Boeve BF, O’Connor HM, Petersen RC (2010) Vegetables, unsaturated fats, moderate alcohol intake, and mild cognitive impairment. DementGeriatrCognDisord 29:413–423.doi: 10.1159/000305099.

    CAS  Google Scholar 

  20. 20.

    Gu Y, Luchsinger JA, Stern Y, Scarmeas N (2010) Mediterranean Diet, inflammatory and metabolic biomarkers, and risk of Alzheimer’s Disease. Journal of Alzheimer’s Disease 22:483–492.doi: 10.3233/JAD-2010-100897.

    PubMed  CAS  Google Scholar 

  21. 21.

    Vercambre MN, Grodstein F, Berr C, Kang JH (2012) Mediterranean Diet and Cognitive Decline in Women with Cardiovascular Disease or Risk Factors. J Acad Nutr Diet 112:816–823.doi: 10.1016/j.jand.2012.02.023

    PubMed  Article  Google Scholar 

  22. 22.

    Cherbuin N, Anstey KJ (2012) The Mediterranean diet is not related to cognitive change in a large prospective investigation: The PATH through life study. Am J Geriatr Psychiatry 20:635–639.doi: 10.1097/JGP.0b013e31823032a9.

    PubMed  Article  Google Scholar 

  23. 23.

    Cherbuin N, Kumar R, Anstey K (2011) Caloric intake but not the Mediterranean diet, is associated with cognition and mild cognitive impairment Alzheimer’s and Dementia. 2011;7:S691.

    Article  Google Scholar 

  24. 24.

    McMillan L, Owen L, Kras M, Scholey A (2011) Behavioural effects of a 10-day Mediterranean diet. Results from a pilot study evaluating mood and cognitive performance. Appetite56:143–147.doi: 10.1016/j.appet.2010.11.149.

    PubMed  Article  Google Scholar 

  25. 25.

    Zazpe I, Sanchez-Tainta A, Estruch R, Lamuela-Raventos RM, Schröder H, Salas-Salvado J, Corella D, Fiol M, Gomez-Gracia E, Aros F, Ros E, Ruíz-Gutierrez V, Iglesias P, Conde-Herrera M, Martinez-Gonzalez MA (2008) A large randomized individual and group intervention conducted by registered dietitians increased adherence to Mediterranean-type diets: the PREDIMED study. J Am Diet Assoc. 108:1134–1145.doi: 10.1016/j.jada.2008.04.011.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Fernández-Ballart JD, Piñol JL, Zazpe I, Corella D, Carrasco P, Toledo E, Perez-Bauer M, Martínez-González MA, Salas-Salvadó J, Martín-Moreno JM (2010) Relative validity of a semi-quantitative food-frequency questionnaire in an elderly Mediterranean population of Spain. Br J Nutr 103:1808–1816.doi: 10.1017 /S0007114509993837.

    PubMed  Article  Google Scholar 

  27. 27.

    de la Fuente-Arrillaga C, Vázquez Z, Bes-Rastrollo M, Sampson L, Martínez-González MA (2009) Reproducibility of a Food Frequency Questionnaire (FFQ) validated in Spain. Public Health Nutr 13:1364–1372.doi: 10.1017/S1368980009993065.

    Article  Google Scholar 

  28. 28.

    Folstein MF, Folstein SE, McHugh PR (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Blesa R, Pujol M, Aguilar M, Santacruz P, Bertran-Serra I, Hernández G, Sol JM, Peña-Casanova J; NORMACODEM Group. NORMAlisation of Cognitive and Functional Instruments for DEMentia (2001) Clinical validity of the’ minimentalstate’ for Spanishspeaking communities. Neuropsychologia 39: 1150–1157.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Freedman M, Leach L, Kaplan E, Winocur G, Shulman K, Dean DC (1994) Clock Drawing A Neuropsychological Analysis. New York, Oxford University Press.

    Google Scholar 

  31. 31.

    del Ser Quijano T, García de Yébenes MJ, Sánchez Sánchez F, FradesPayo B, Rodríguez Laso A, BartoloméMartínez MP, Otero Puime A (2004) Cognitive assessment in the elderly. Normative data of a Spanish population sample older than 70 years. Med Clin (Barc)122:727–740.

    Article  Google Scholar 

  32. 32.

    Wechsler D (1945) A standardized memory scale for clinical use. J Psychol 19:87–95.

    Article  Google Scholar 

  33. 33.

    Rey A (1958) L’examen Clinique en Psychologie, Presses Universitaires de France, Paris.

    Google Scholar 

  34. 34.

    Rey, A (1941) L’examen psychologique dans les cas d’encéphalopathie traumatique. Archives de Psychologie 28:286–340.

    Google Scholar 

  35. 35.

    Osterrieth, PA (1944). Le test de copie d’une figure complexe: Contribution è l’étude de la perception et la mémoire. Archives de Psychologie 30:286–356.

    Google Scholar 

  36. 36.

    Peña-Casanova J, Gramunt-Fombuena N, Quiñones-Ubeda S, Sánchez-Benavides G, Aguilar M, Badenes D, Molinuevo JL, Robles A, Barquero MS, Payno M, Antúnez C, Martínez-Parra C, Frank-García A, Fernández M, Alfonso V, Sol JM, Blesa R; NEURONORMA Study Team (2009) SpanishMulticenterNormativeStudies (NEURONORMAProject): normsfortheRey-Osterriethcomplexfigure (copy and memory), and free and cuedselectiveremindingtest. Arch Clin Neuropsychol.24:371–393.doi: 10.1093/arclin/acp041

    PubMed  Article  Google Scholar 

  37. 37.

    Kaplan, EF, Goodglass H, Weintraub, S (1983). The Boston naming test. Philadelphia: Lippincott Williams & Wilkins

    Google Scholar 

  38. 38.

    Peña-Casanova J, Quiñones-Ubeda S, Gramunt-Fombuena N, Aguilar M, Casas L, Molinuevo JL, Robles A, Rodríguez D, Barquero MS, Antúnez C, Martínez-Parra C, Frank-García A, Fernández M, Molano A, Alfonso V, Sol JM, Blesa R; NEURONORMAStudy Team (2009) SpanishMulticenterNormativeStudies ((NEURONORMAProject): norms for Bostonnamingtest and token test. Arch Clin Neuropsychol 24:343–354.doi: 10.1093/arclin/acp039.

    PubMed  Article  Google Scholar 

  39. 39.

    Ramier, AM, Hécaen, H (1970) Respective roles of frontal lesions and lesion lateralization in “verbal fluency” deficiencies. Revue Neurologique; 132:17–22.

    Google Scholar 

  40. 40.

    Peña-Casanova J, Quiñones-Ubeda S, Gramunt-Fombuena N, Quintana-Aparicio M, Aguilar M, Badenes D, Cerulla N, Molinuevo JL, Ruiz E, Robles A, Barquero MS, Antúnez C, Martínez-Parra C, Frank-García A, Fernández M, Alfonso V, Sol JM, Blesa R; NEURONORMAStudy Team (2009) SpanishMulticenterNormativeStudies ((NEURONORMAProject): normsfor verbal fluency tests. ArchClinNeuropsychol 24:395–411.doi: 10.1093/arclin/acp042

    Google Scholar 

  41. 41.

    Benton AL, Hamsher K (1976) Multilingual aphasia examination. Iowa City: University of Iowa.

    Google Scholar 

  42. 42.

    Rami L, Serradell M, Bosch B, Villar A, Molinuevo JL (2007) Standard values of frontal cognitive functioning tests for those over 60 years of age Rev Neurol 45:268–271.

    PubMed  CAS  Google Scholar 

  43. 43.

    Wechsler D (1999) Escala de inteligencia de Wechsler para Adultos-III (WAIS III), TEA Ediciones, Madrid.

    Google Scholar 

  44. 44.

    Peña-Casanova J, Quiñones-Ubeda S, Quintana-Aparicio M, Aguilar M, Badenes D, Molinuevo JL, Torner L, Robles A, Barquero MS, Villanueva C, Antúnez C, Martínez-Parra C, Frank-García A, Sanz A, Fernández M, Alfonso V, Sol JM, Blesa R; NEURONORMA Study Team (2009) Spanish Multicenter Normative Studies (NEURONORMAProject): normsfor verbal span, visuospatialspan, letter and numbersequencing, trailmaking test, and symbol digitmodalities test. Arch Clin Neuropsychol 24:321–341.doi: 10.1093/arclin/acp038.

    PubMed  Article  Google Scholar 

  45. 45.

    Crowe SF (1998) The differential contribution of mental tracking, cognitive flexibility, visual search, and motor speed to performance on parts A and B of the Trail Making Test. Journal of Clinical Psychology 54: 585–591.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Wechsler D (1981) WAIS-R: manual. New York: The Psychological Corporation.

    Google Scholar 

  47. 47.

    Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL (1982) A new clinical scale for the staging ofdementia. Br J Psychiatry 140:566–572.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Mahoney FI, Barthel DW (1965) Functional evaluation: the Barthel index. Md State Med J 14:61–65.

    PubMed  CAS  Google Scholar 

  49. 49.

    Lawton MP, Brody EM (1969). Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186.

    PubMed  Article  CAS  Google Scholar 

  50. 50.

    Blessed G, Tomlinson BE, Roth M. (1968)The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 114:797–811.

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Bäckman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC (2004) Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246.

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington.

    Google Scholar 

  53. 53.

    Elosua R, Marrugat J, Molina L, Pons S, Pujol E (1994) Validation of the Minnesota Leisure Time Physical Activity Questionnaire in Spanish men. The MARATHOM Investigators. Am J Epidemiol 139:1197–1209.

    PubMed  CAS  Google Scholar 

  54. 54.

    Elosua R, Garcia M, Aguilar A, Molina L, Covas MI, Marrugat J (2000) Validation of the Minnesota Leisure Time Physical Activity Questionnaire In Spanish Women. Investigators of the MARATDOM Group. Med Sci Sports Exerc 32:1431–1437.

    Article  CAS  Google Scholar 

  55. 55.

    Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with Hhal. J Lipid Res 31:545–548

    PubMed  CAS  Google Scholar 

  56. 56.

    Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. Roy. Statist. Soc. Ser. B 57:289–300.

    Google Scholar 

  57. 57.

    Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, D’Armiento M, D’Andrea F, Giugliano D (2004) Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 292:1440–1446.

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Hermsdorff HH, Zulet MA, Puchau B, Martínez JA (2010) Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study. NutrMetab (Lond) 7:42.doi: 10.1186/1743-7075-7-42.

    Article  Google Scholar 

  59. 59.

    Vassiliou EK, Gonzalez A, Garcia C, Tadros JH, Chakraborty G, Toney JH (2009) Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems. Lipids Health Dis 8:25.doi: 10.1186/1476-511X-8-25.

    PubMed  Article  Google Scholar 

  60. 60.

    López-Miranda J, Pérez-Jiménez F, Ros E, De Caterina R, Badimón L, Covas MI, Escrich E, Ordovás JM, Soriguer F, Abiá R, de la Lastra CA, Battino M, Corella D, Chamorro-Quirós J, Delgado-Lista J, Giugliano D, Esposito K, Estruch R, Fernandez-Real JM, Gaforio JJ, La Vecchia C, Lairon D, López-Segura F, Mata P, Menéndez JA, Muriana FJ, Osada J, Panagiotakos DB, Paniagua JA, Pérez-Martinez P, Perona J, Peinado MA, Pineda-Priego M, Poulsen HE, Quiles JL, Ramírez-Tortosa MC, Ruano J, Serra-Majem L, Solá R, Solanas M, Solfrizzi V, de la Torre-Fornell R, Trichopoulou A, Uceda M, Villalba-Montoro JM, Villar-Ortiz JR, Visioli F, Yiannakouris N (2010) Olive oil and health: Summary of the II International Conference on Olive Oil and Health consensus report, Jaen and Córdoba (Spain) 2008. Nutr MetabCardiovasc Dis 20:284–294.doi: 10.1016/j.numecd.2009.12.007.

    Article  Google Scholar 

  61. 61.

    Mancini M, Parfitt VJ, Rubba P (1995) Antioxidants in the Mediterranean diet. Can J Cardiol 11:105G–109G.

    PubMed  CAS  Google Scholar 

  62. 62.

    Hermsdorff HH, Barbosa KB, Volp AC, Puchau B, Bressan J, Zulet MÁ, Martínez JA (2012) Vitamin C and fibre consumption from fruits and vegetables improves oxidative stress markers in healthy young adults. Br J Nutr 107:1119–1127.doi: 10.1017/S0007114511004235

    PubMed  Article  CAS  Google Scholar 

  63. 63.

    Razquin C, Martinez JA, Martinez-Gonzalez MA, Mitjavila MT, Estruch R, Marti A (2009) A 3-year follow-up of a Mediterranean diet rich in virgin olive oil is associated with high plasma antioxidant capacity and reduced body weight gain. Eur J ClinNutr 63:1387–1393 doi: 10.1038/ejcn.2009.106

    Article  CAS  Google Scholar 

  64. 64.

    Valls-Pedret C, Lamuela-Raventós RM, Medina-Remón A, Quintana M, Corella D, Pintó X, Martínez-González MÁ, Estruch R, Ros E (2012) Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis 29:773–782.doi: 10.3233/JAD-2012-111799.

    PubMed  CAS  Google Scholar 

  65. 65.

    Berr C, Portet F, Carriere I, Akbaraly TN, Feart C, Gourlet V, Combe N, Barberger-Gateau P, Ritchie K(2009) Olive oil and cognition: results from the three-city study. Dement Geriatr Cogn Disord 28:357–364.doi: 10.1159/000253483

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Nooyens AC, Bueno-de-Mesquita HB, van Boxtel MP, van Gelder BM, Verhagen H, Verschuren WM (2011) Fruit and vegetable intake and cognitive decline in middleaged men and women: the Doetinchem Cohort Study. Br J Nutr 106:752–761.doi: 10.1017/S0007114511001024

    PubMed  Article  CAS  Google Scholar 

  67. 67.

    Porta N, Bonet C, Cobo E (2007) Discordance between reported intention-to-treat and per protocol analyses. J Clin Epidemiol 60:663–669

    PubMed  Article  Google Scholar 

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Correspondence to Elena H. Martinez-Lapiscina.

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Martinez-Lapiscina, E.H., Clavero, P., Toledo, E. et al. Virgin olive oil supplementation and long-term cognition: the Predimed-Navarra randomized, trial. J Nutr Health Aging 17, 544–552 (2013). https://doi.org/10.1007/s12603-013-0027-6

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Key words

  • Mediterranean diet
  • olive oil
  • randomized controlled trial
  • cognition
  • mild cognitive impairment