May/June 2018

Mediterranean Diet Improves Cognition, Memory, and Brain Volume
By KC Wright, MS, RDN
Today's Geriatric Medicine
Vol. 11 No. 3 P. 16

Research indicates that a healthful eating pattern, such as that of the Mediterranean diet, offers a protective effect on brain health and is correlated with a decreased rate of cognitive decline and a lower risk of cognitive impairment.

As life expectancy has increased to 78.8 and birth rates have decreased, the aging population has grown vastly in the United States.1 In 2012, the population of Americans aged 65 and older was estimated at 43 million and predicted to experience monumental growth—almost doubling by the year 2050 to more than 83 million people.2

Among older adults, dementia, a major noncommunicable cause of disability and dependency, results in difficulty in remembering, thinking clearly, making decisions, and/or controlling emotions. Although the prevalence of dementia in the United States declined significantly between 2000 and 2012,3 about 50 million people worldwide have dementia, and nearly 10 million new cases are diagnosed each year.4 Much of this increase is attributable to the rising numbers of those with dementia living in low- and middle-income countries. Alzheimer's disease (AD) is the most common form of dementia, accounting for 60% to 75% of all cases.

The Mediterranean diet (MedDiet) is well known for its cardiovascular and anti-inflammatory benefits and its association with healthy aging and reduced risk for certain cancers, type 2 diabetes, and Parkinson's disease.5-7 Newer research suggests this healthy eating pattern also protects brain health, and specifically, that a greater adherence to the MedDiet is correlated with a slower rate of cognitive decline,8,9 lower risk of cognitive impairment,10,11 and lower risk of dementia.8,11 Some of these research findings are conflicting,12-14 mainly due to differences in the populations studied as well as the methodologies used. Yet two clinical trials with long-term follow up support the association between the MedDiet and cognitive performance.15,16

Akin to the MedDiet, the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet factors in other foods based on evidence of the effect of diet on dementia, suggesting that the MIND diet may be more predictive of cognitive decline than the MedDiet.17 As a hybrid diet, MIND awards points for reduced consumption of specific foods known to be harmful to the brain such as red meat, butter and stick margarine, cheese, pastries and sweets, and fried and fast food.

The MedDiet and MIND diet both recommend a high intake of plant foods, limited meat consumption, moderate intake of alcohol (wine in particular), and use of extra virgin olive oil as a primary fat source. Both dietary patterns are rich in antioxidants along with monounsaturated fats and omega-3 fats that have been associated with a lower risk of cognitive decline and dementia.8 Similarly, the MedDiet and MIND diet are both low in saturated fats that have been shown to increase the risk of cognitive decline and dementia. The MedDiet places greater emphasis on fish and overall fruit and vegetable intake. Unique to the MIND diet, leafy green vegetables and berries specifically are independently reported to be neuroprotective.18

Previous research on the influence of diet on cognition has focused on dementia as the major clinical outcome and to a lesser extent, on detailed cognitive functioning. Other studies have evaluated cognitive function using a relatively limited cognitive assessment battery without exploring particular cognitive domains.14,19-21 Some studies on aging populations have shown associations between higher adherence to the MedDiet and larger brain volumes.21-23 Other compelling studies reviewed here strongly reinforce the link between the MedDiet and MIND scores and healthier brain structure and function.24-26

Improved Cognitive Function
In August 2017, the Journal of the American Geriatrics Society published research results evaluating the association between the MedDiet and MIND scores and neurodegeneration.24 Cognitive performance was objectively measured among 5,907 American community-dwelling adults sampled from the nationally representative population-based Health and Retirement Study.27 Dietary intake was assessed using an extensively validated semiquantitative 163-item food frequency questionnaire (FFQ).

Adherence to both the MedDiet and MIND was determined by selecting the dietary components of the FFQ relevant to each dietary pattern. Individual scores were then assigned for the foods based on the frequency of recommended intakes. Scores of dietary components consistent with the MedDiet—whole grains, fruits, vegetables, legumes, fish, olive oil, and up to two alcoholic drinks daily—were overall higher, with better adherence to the traditional MedDiet. Conversely, for foods not characteristic of a MedDiet—red meat, poultry, full-fat dairy—scores decreased as consumption of these foods increased. The MIND diet scores were calculated similarly to the MedDiet but also measured intakes of green leafy vegetables, nuts, berries, beans, and poultry, which are associated with better adherence to the diet. Dietary intakes of the additional foods in the MIND diet considered unhealthy to the brain (including pastries and sweets along with fried and fast foods) received lower scores.

Cognitive function was assessed using a global cognition score comprising three items: immediate and delayed recall of 10 words from a random list, backward counting, and serial seven subtraction. Mean scores indicated that overall there was moderate adherence to both dietary patterns. Study participants with high adherence to either the MedDiet or the MIND diet had significantly better cognitive performance than those with mid or low levels of adherence. Individuals with the highest diet adherence had significantly better cognitive scores for both diets with a dose-response relationship.

This study's large sample size and older adult community-based population, along with the validated FFQ, are strengths of these findings. Obviously, the nature of a cross-sectional design makes it impossible to establish a causal relationship between diet and cognition. Yet the findings of this study are supported by results from the Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Trial substudy16 that demonstrated small but significantly better cognitive function in response to greater MedDiet adherence.

Improved Memory
Results from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD) study published in August 2017 by PLoS One explored the comprehensive relationship between the MedDiet pattern and its components with specific domains of cognitive functioning.25 A random sampling of 1,864 participants aged 64 and older from two cities in Greece were recruited, given physical exams, evaluated for dementia, and assessed for activities of daily living. A structured memory complaint questionnaire was used to assess subjective memory problems and forgetfulness. Participants received a comprehensive neuropsychological assessment including all major cognitive domains. Also assessed were clinical comorbidities, education, and ApoE genotyping (an adjunct test in the diagnosis in probable late onset AD in symptomatic adults).

Dietary intake was evaluated with a semiquantitative FFQ that had been validated for the Greek population. Subject responses were converted to daily intakes of specific foods and then extrapolated into macronutrient and energy intakes. Dietary intake was also organized into food groups identifying the core foods of the Greek diet. Adherence to the MedDiet was evaluated on weekly consumption of 11 food groups that closely characterize the Mediterranean pattern, including nonrefined cereals, fruits, vegetables, legumes, fish, and olive oil. MedDiet scores were based on weighting of selected foods compared with frequency of consumption.

Of the participants in this analysis, 90 (5%) were diagnosed with dementia, of whom 68 were diagnosed with AD and were excluded from regression analyses. The participants diagnosed with dementia had slightly lower total MedDiet scores compared with individuals without dementia. No differences were found between groups in macronutrient intake expressed as calorie percentages; however, subjects with dementia consumed less total protein daily.

With the exception of attention and speed, all other cognitive domains—including memory, language, and executive functioning—were positively associated with the MedDiet. Through further statistical analyses, the researchers suggested that every four-unit increase in the MedDiet score could counterbalance the negative effect of one year of cognitive aging.

Lower dietary intakes of fruits, vegetables, and fish were seen in individuals with dementia as compared with those without the disease. A significant association was observed between cognitive status (with or without dementia) and fish consumption, suggesting that for every serving of fish per day, a reduction in risk of dementia by almost 70% was observed or, alternatively, one serving of fish per week was associated with an almost 10% reduction in dementia risk. The total composite diet score was positively associated with nonrefined cereal consumption, suggesting the beneficial effect on cognitive performance with just one additional serving of whole grains daily could outweigh the detrimental effect of 1.4 years of cognitive aging, especially memory.

These HELIAD results help to extend the current knowledge by establishing a positive association between adherence to the MedDiet and cognitive function. Although precautions were taken to limit food consumption misreporting, the FFQ data may not be precise if reported by individuals with cognitive impairment. However, these results are strengthened by the comprehensive neuropsychological evaluations and the scoring system to assess for MedDiet intake.

Structural Brain Change
In January 2017, Neurology published results describing the association between the MedDiet and multiple indices of brain structural aging.26 The 562 subjects who were recruited lived independently in the community, were relatively healthy, and were free of dementia. Participants, all approximately aged 70 at baseline, were part of Scotland's Lothian Birth Cohort study of 1936, which initially tested their intelligence at the age of 11 and retested them throughout the life course to study determinants of nonpathological cognitive aging.28

Dietary data were collected at baseline via a 168-item FFQ and used to construct a MedDiet score. Approximately three and six years later subjects underwent a structural MRI brain scan. Cognitive assessments were made at all three wave time points. Education, anthropometric data, and a medical history were assessed.

Results from this study indicate that greater adherence to the MedDiet is protective against total brain atrophy, replicating results from three previous studies. The study authors note that the task of identifying specific foods and nutrients that have direct functional effects on total brain atrophy is formidable. It has been argued that it is the synergistic effects of contributing food components and their interactions that offer the increased benefits to brain health.29

Although diet was sampled at a single time point, MedDiet scores have been shown to be high over intervals of more than seven years with or without dementia.30 The effect of the MedDiet on brain atrophy was significant when controlled for education. The study authors suggest that, because education was controlled and the effect was still significant, the MedDiet "is not simply a function of healthier lifestyle choice in more educated or intelligent individuals, who tend to have larger brain volumes."26

The age and ethnic homogeneity of the study participants gave strength to this study, reducing confounders with brain change and diet. In addition, diet was measured three years prior to the first MRI images so that any neurodegeneration correlated with brain structure is doubtful for diet bias. This might suggest that the MedDiet effect is causal. Lead author in this study, Michelle Luciano, PhD, of the University of Edinburgh, comments, "Some might argue that we are detecting reverse causation—that brain change causes diet choice—a deteriorating brain would cause people to follow less healthy diets, but because our measures were collected three years before the brain imaging, this variable seems unlikely."

Proposed Mechanism of Action
The biological mechanisms for how the MedDiet may influence brain health are not yet clear. Aside from vascular health and antioxidant and anti-inflammatory pathways, beneficial effects specific to the MedDiet may also include neuronal cell signaling.29 Other research suggests that the MedDiet may be associated with reduced brain infarcts31 and a lower white matter hyperintensity volume32 in elderly individuals. Authors of the HELIAD study suggest that research with more robust design, particularly clinical trials, will identify these associations and elucidate the mechanisms by which the MedDiet, or its components, exert their potential health-enhancing effects on the nervous system.25

Due to the complex biological interactions between the many different constituents that compose our food and diet, it may be difficult to identify specific nutrients that have an independent effect. Luciano points to the potential of omega-3 fats or perhaps even the way foods are prepared. It stands to reason that the whole-diet approach may be best for understanding the role of diet, as the synergistic effect of food and nutrients may show the most benefit. Specifically, the MedDiet style of eating comprises a rich plethora of nutrients with many that may have independent mechanisms of action, which, when taken together, protect the brain.

MedDiet as a Public Health Initiative
A review of the ongoing research surrounding a MedDiet style of eating and brain health is important as life expectancy continues to increase along with concerns about dementia. The studies summarized here build on earlier research that investigated a relationship between dietary patterns and brain health. Individuals with the highest adherence to neuroprotective diets had a 30% to 35% lower risk of cognitive impairment.24 These new findings affirm support that diet modification may be an important public health strategy to protect against AD and other dementias.

The 2015 World Health Organization report suggests that although 70 may not yet appear to be the new 60, with dedicated public health action on aging, it may be closer to a reality in the future.1 Considering that the ages of geriatric patients could potentially span from 65 to well over 100, it's important that both primary care providers and geriatricians discuss with their patients the potential of the MedDiet on brain health. Given the systemic benefits of consuming a MedDiet, including brain and heart health and the reduced risk for certain cancers, type 2 diabetes, and Parkinson's disease, it may be prudent for primary care providers to prescribe the diet early in the lifecycle or at least beginning with young adults.

Many adults, both old and young, fear their own potential for developing AD or other dementias. Thus, it's critical to share with patients that nutrition is an important and modifiable influence on cognition with aging, and something with which patients can be proactive, developing modifications for healthful benefits all around.

Claire McEvoy, PhD, MPhil, RD, an epidemiologist and clinical dietitian at Queen's University Belfast and the lead author on the August 2017 Journal of the American Geriatrics Society article notes that study participants with the greatest MedDiet adherence were younger and more physically active, were less likely to be hypertensive and obese or have diabetes and depression, and had higher education levels. As noted earlier, the incidence of dementia is increasing among those in lower and middle income countries, so it's important to consider access to community resources for education and possibly community-supported agriculture and edible gardens.

Nutrition Practice Points in the Clinic
When considering strategies and formulating messages to counsel patients in the clinical setting, it's important to consider current trends in diet consumption among Americans. While whole grains and plant foods have high antioxidant potential, about 75% of the US population has an eating pattern that's low in fruits, vegetables, and plant oils. And most Americans exceed recommended limits on sugar and saturated fats.33

A recent prospective study of an older US community population showed that consumption of green leafy vegetables was linearly associated with slower cognitive decline. In fact, the rate of cognitive decline among those who consumed one to two servings per day of green leafy vegetables such as spinach, kale, collards, and lettuce was the equivalent of being 11 years younger when compared with those who rarely or never consumed green leafy vegetables.34 Thus, the addition of a daily serving of green leafy vegetables to the diet may be a simple way to contribute to brain health.

In the HELIAD study, both fish and whole grains—mainstays of the MedDiet—were associated with better cognitive performance. The subjects with dementia in this study also had lower protein intakes, suggesting it may be prudent to educate and encourage older adults to consume adequate amounts of protein daily.

Few randomized trials or epidemiologic studies have found a protective benefit of dietary supplements against cognitive decline, adding strength to thoughts that cognitive benefits are derived from whole food nutrients.34 The 2018 US News & World Report's ranking of popular diets—assessed by a panel of health experts—found a tie between the top-ranked Mediterranean and DASH diets for best overall in being healthy and easy to follow.35

Although nutrition is modifiable, it can be difficult for many patients to change behaviors, especially surrounding food intake. Primary care providers and geriatricians can readily provide patients with a diet prescription handout detailing the MedDiet. Oldways, a nonprofit food and nutrition education organization, partnered with the Harvard T.H. Chan School of Public Health to develop the traditional Mediterranean Diet Pyramid for both the public and health professionals.36 Along with MedDiet prescription pads, they offer excellent educational materials, including a four-week MedDiet menu, grocery lists, and brochures. Finally, patients should be referred to a registered dietitian nutritionist who employs counseling techniques based on individual health and needs to adapt new behaviors to practice the MedDiet for life.

— KC Wright, MS, RDN, is the principal at Wildberry Communications. With decades of clinical, academic, and research experience, she is extensively published.

MEDITERRANEAN DIET CORE FOODS
• Whole grains
• Vegetables, especially leafy greens
• Fruits
• Legumes
• Herbs
• Spices
• Nuts
• Extra virgin olive oil
• Fish/seafood
• Low-fat dairy
• Wine (in moderation)

References
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