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Original Investigation |

Mediterranean Diet and Age-Related Cognitive Decline A Randomized Clinical Trial

Cinta Valls-Pedret, MSc1,2; Aleix Sala-Vila, DPharm, PhD1,2; Mercè Serra-Mir, RD1,2; Dolores Corella, DPharm, PhD2,3; Rafael de la Torre, DPharm, PhD2,4; Miguel Ángel Martínez-González, MD, PhD2,5; Elena H. Martínez-Lapiscina, MD, PhD2,5; Montserrat Fitó, MD, PhD2,4; Ana Pérez-Heras, RD1,2; Jordi Salas-Salvadó, MD, PhD2,6; Ramon Estruch, MD, PhD2,7; Emilio Ros, MD, PhD1,2
[+] Author Affiliations
1Lipid Clinic, Department of Endocrinology and Nutrition, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain
2Ciber Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
3Department of Preventive Medicine, University of Valencia, Valencia, Spain
4Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain
5Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain
6Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain
7Department of Internal Medicine, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain
JAMA Intern Med. 2015;175(7):1094-1103. doi:10.1001/jamainternmed.2015.1668.
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Importance  Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking.

Objective  To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet.

Design, Setting, and Participants  Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study.

Interventions  Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat).

Main Outcomes and Measures  Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global.

Results  Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (−0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (−0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and −0.17 (−0.32 to −0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (−0.25 to 0.31), and −0.33 (−0.57 to −0.09). Changes from baseline of the global cognition composite were 0.05 (−0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, −0.05 (−0.27 to 0.18) for the Mediterranean diet plus nuts, and −0.38 (−0.57 to −0.18) for the control diet. All cognitive composites significantly (P < .05) decreased from baseline in controls.

Conclusions and Relevance  In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function.

Trial Registration  isrctn.org Identifier: ISRCTN35739639

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Figure 1.
Flow Diagram of the Study

MCI indicates mild cognitive impairment.

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Figure 2.
Changes in Cognitive Function Measured With Composites by Intervention Group

Error bars indicate 95% CIs. P values by analysis of covariance were adjusted for sex, baseline age, years of education, marital status, APOE ε4 genotype, ever smoking, baseline body mass index, energy intake, physical activity, type 2 diabetes mellitus, hyperlipidemia, ratio of total cholesterol to high-density lipoprotein cholesterol, statin treatment, hypertension, use of anticholinergic drugs, and time of follow-up, with the Bonferroni post hoc test. For each cognitive composite, the changes between the 2 Mediterranean arms were not statistically different (P >.99 for all). The changes for memory between the Mediterranean diet plus olive oil and control groups and for frontal and global cognition between the Mediterranean diet plus nuts and control groups had values of P < .25.

aP < .05.

bP < .01.

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Submit a Comment
1 liter of EVOO a week?
Posted on May 14, 2015
Daniel B Vance, MD, FACP, HMDC
SkyRidge Medical Center, Cleveland TN, USA
Conflict of Interest: No conflict.
The article reports that the subjects were given one liter of olive oil a week, early they did not actually consume that much. That would be 9.66 tablespoons per day which would be 1,150 calories per day. In the video accompanying the article Dr. Ros mentions 5 tablespoons of olive oil per day which still would amount to 600 extra calories per day. It's hard to imagine anyone consuming that many fat calories for several years and remaining healthy. The article does not indicate how much olive oil the subjects actually consumed but the news media is reporting the 1 L per week figure. Please offer some follow-up clarification on this question.
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