Med Diet With Nuts, Olive Oil Linked to Better Cognition

Pauline Anderson

May 13, 2015

Adding nuts and olive oil to a Mediterranean diet could protect cognitive function in older adults, new research suggests.

The study showed that adding nuts to the Mediterranean diet boosted measures of memory, while supplementing the diet with extra-virgin olive oil improved global and frontal cognition.

The results suggest that nutritional interventions to protect brain function should be started "at the preclinical stage, before any impairment," even in older adults, said study author Emilio Ros, MD, PhD, consultant, Endocrinology Department, Hospital Clinic, Barcelona, Spain.

Dr Emilio Ros

"Our participants were cognitively healthy to start with. We believe that if they had been cognitively impaired, we wouldn't have seen any effect."

The study was published online May 11 in JAMA Internal Medicine.


The analysis was conducted on a subcohort of the Prevención con Dieta Mediterránea (PREDIMED), a 5-year randomized clinical trial of nutrition intervention, the main analysis of which was previously published in the New England Journal of Medicine. PREDIMED compared the cardiovascular effect of the Mediterranean diet with added mixed nuts or olive oil, and a control diet that encouraged reduced dietary fat, in older adults at high cardiovascular risk.

The study participants had type 2 diabetes or at least three of five cardiovascular risk factors: smoking, hypertension, dyslipidemia, overweight or obesity, and family history of early-onset coronary heart disease.

The current analysis looked at the effect of the diets on cognition. It included 127 participants in a receiving a Mediterranean diet plus olive oil, 112 in a group receiving a Mediterranean diet plus nuts, and 95 in a control group. The mean age of participants was 66.8 years, and 50.9% were women.

Those in the olive oil group received 1 L of olive oil per week. Those in the nuts group got 30 g of mixed nuts per day (walnuts, hazelnuts, and almonds). The control group was given advice to reduce their dietary fat.

The study participants were seen quarterly. (The control group was seen annually for the first 3 years of the trial, but the protocol was changed to annual visits because the more infrequent visits could be considered a limitation of the trial).

Participants underwent neuropsychological tests at baseline and near the study's termination (follow-up times varied, but the mean follow-up was 4.1 years). Tests included the Mini-Mental State Examination (MMSE), which assesses global cognitive function; the Rey Auditory Verbal Learning Test, which rates immediate and delayed episodic verbal memory; and the verbal paired associates test, a subtest of the Wechsler Memory Scale that evaluates episodic memory performance. The researchers later added tests to assess changes in language and frontal functions.

Researchers calculated three composite scores of cognitive function: memory, frontal functions (which included tests measuring attention, cognitive flexibility, and working memory), and global cognition.

While 447 participants underwent these tests at baseline, 113 (25.3%) did not complete the second procedure. Demographic and cardiovascular factors did not significantly differ between those who did and did not complete the study, although there were more APOE ε4 allele carriers and worse cognitive scores on the MMSE and Wechsler Memory Scale among those who withdrew from the study.

Dietary data were collected during face-to-face interviews by using a validated 137-item food-frequency questionnaire.

The researchers found that compared with the control group, the memory composite improved significantly in the group receiving the Mediterranean diet plus nuts (mean composite change, 0.09; 95% confidence interval [CI], –0.05 to 0.23; P = .04).

In the group receiving the Mediterranean diet plus olive oil, frontal cognition (mean composite change, 0.23; 95% CI, 0.03 - 0.43; P = .003) and global cognition (mean composite change, 0.05; 95% CI, –0.11 to 0.21; P = .005) improved significantly compared with control diet scores.

Changes in each composite were more similar when the two Mediterranean diet groups were compared than when either of these diets was compared with the control diet. This, said Dr Ros, suggests that both diets are protective.

The benefit of the Mediterranean diet was independent of sex, age, energy intake, and cognition-related variables, such as educational level, APOE ε4 genotype and vascular risk factors.

At the end of the follow-up, researchers identified 37 cases of incident mild cognitive impairment: 17 (13.4%) in the olive oil group, 8 (7.1%) in the nuts group, and 12 (12.6% in the control group) (adjusted P = .28). There were no documented cases of dementia.

The results are consistent with those of large observational studies, providing longitudinal evidence of a moderate protective effect of the Mediterranean diet against cognitive decline. But the new scientific evidence is stronger because it's from a randomized trial; according to Dr Ros, this is the first such randomized trial.

Antioxidant Effect

The beneficial cognitive effects seen in the study probably come from the antioxidant and anti-inflammatory elements of the foods in the two Mediterranean diet groups, the researchers speculate. Olive oil and nuts are rich in phenolic compounds that might counteract oxidative process in the brain, leading to neurodegeneration. Polyphenols in the foods can also improve cerebrovascular blood flow, modulate neuronal signaling, enhance synthesis of neurotrophic factors, and stimulate neurogenesis.

Vascular improvement is another mechanism by which the Mediterranean diet might promote brain health. MRI studies have found a strong beneficial effect of this diet on white matter hyperintensities and subclinical brain infarcts.

The authors noted that the Mediterranean diet reduced the incidence of cardiovascular disease by 30% compared with the control diet in the original PREDIMED study, and that stroke risk was reduced by 34% in the olive oil group and by 49% in the nuts group. The diets also had a beneficial effect on blood pressure and diabetes risk.

Because the low-fat control diet probably mirrored the Mediterranean diet in many respects (because all participants were European), the benefits of the two Mediterranean diet groups were probably due to the added nuts or olive oil, said Dr Ros.

If nuts and olive oil are cognitively beneficial, why didn't the study include an arm with both added to the Mediterranean diet? Dr Ros explained that the study was designed in 2003, when a healthy diet was considered to be low fat; both olive oil and nuts are relatively high in fat.

"We didn't dare put too much fat in a study arm," he said. "We also worried there wouldn't be as much compliance if participants were asked to add both nuts and olive oil."

"Modest" Results

Asked to comment, David Knopman MD, professor of neurology at the Mayo Clinic College of Medicine in Rochester, Minnesota, doing research in late-life cognitive disorders, noted some of the study's strengths, including the "good but not great" sample sizes, the duration of follow-up, and the fact that it appears to be the only such randomized, controlled trial of the Mediterranean diet aside from the parent PREDIMED study.

However, said Dr Knopman, the results were "very, very modest." On nine test scores, there were three changes that "barely met the P less than .05 criteria, apparently mainly due to the Mediterranean diet plus olive oil treatment," he said. 

Dr Knopman also noted other "real weaknesses" of the trial. For example, the dropout rate was high (although the higher rate in the untreated group would seem to favor the Mediterranean diet groups) and it was of necessity unblinded. 

But his greatest concern is not knowing the proportion of participants who actually adhered to the diet. "The authors provide only group means in the article, which is not adequate. What if only 50% of participants actually used the olive oil or nuts?"

Dr Knopman said that he recognizes the challenges in conducting this type of analysis. For example, in starting with cognitively healthy people, the study was almost certainly underpowered to see an effect on cognition.

The study should be viewed with "great caution," stressed Dr Knopman. Although it's much better than purely observational studies, it is far from providing definitive evidence, he said.

"Personally, I believe that the scientific community has compromised its reputation with the lay public with the conflicting dietary claims and counterclaims that have hit the mainstream media.  A prudent approach would be to say that the definitive studies have yet to be done."

Combining fundamentally weak empiric data with scientifically sounding claims such as "antioxidant," "cerebrovascular blood flow," and "modulation of neuronal signaling" is not good science but "a lot of smoke and mirrors," added Dr Knopman.

"The common-sense notions of a healthy diet that lacks gimmicks ought to be the default until strong evidence to the contrary emerges."

Dr Ros reports receiving research funding and is a nonpaid member of the scientific advisory committee of the California Walnut Commission. Dr Knopman has disclosed no relevant financial relationships.

JAMA Intern Med. Published online May 11, 2015. Abstract


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