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

Cinta Valls-Pedret, Aleix Sala-Vila, Mercè Serra-Mir, Dolores Corella, Rafael de la Torre, Miguel Ángel Martínez-González, Elena H. Martínez-Lapiscina, Montserrat Fitó, Ana Pérez-Heras, Jordi Salas-Salvadó, Ramon Estruch, Emilio Ros

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. To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. 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. 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). 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. 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. In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function. isrctn.org Identifier: ISRCTN35739639.