Mediterranean diet is linked to the lowest risk of cognitive impairment

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According to a recent analysis of data from two major eye disease studies, adherence to the Mediterranean diet – high in vegetables, whole grains, fish, and olive oil – correlates with higher cognitive function.

Dietary factors also seem to play a role in slowing cognitive decline.

Researchers at the National Eye Institute (NEI), part of the National Institutes of Health, led the analysis of data from the Age-Related Eye Disease Study (AREDS) and AREDS2.

They published their results today in the journal Alzheimer’s and Dementia.

“We do not always pay attention to our diets. We need to explore how nutrition affects the brain and the eye” said Emily Chew, M.D., director of the NEI Division of Epidemiology and Clinical Applications and lead author of the studies.

The researchers examined the effects of nine components of the Mediterranean diet on cognition. The diet emphasizes consumption of whole fruits, vegetables, whole grains, nuts, legumes, fish, and olive oil, as well as reduced consumption of red meat and alcohol.

AREDS and AREDS2 assessed over years the effect of vitamins on age-related macular degeneration (AMD), which damages the light-sensitive retina. AREDS included about 4,000 participants with and without AMD, and AREDS2 included about 4,000 participants with AMD.

The researchers assessed AREDS and AREDS2 participants for diet at the start of the studies.

The AREDS study tested participants’ cognitive function at five years, while AREDS2 tested cognitive function in participants at baseline and again two, four, and 10 years later.

The researchers used standardized tests based on the Modified Mini-Mental State Examination to evaluate cognitive function as well as other tests.

They assessed diet with a questionnaire that asked participants their average consumption of each Mediterranean diet component over the previous year.

Participants with the greatest adherence to the Mediterranean diet had the lowest risk of cognitive impairment.

High fish and vegetable consumption appeared to have the greatest protective effect. At 10 years, AREDS2 participants with the highest fish consumption had the slowest rate of cognitive decline.

The numerical differences in cognitive function scores between participants with the highest versus lowest adherence to a Mediterranean diet were relatively small, meaning that individuals likely won’t see a difference in daily function.

But at a population level, the effects clearly show that cognition and neural health depend on diet.

The researchers also found that participants with the ApoE gene, which puts them at high risk for Alzheimer’s disease, on average had lower cognitive function scores and greater decline than those without the gene.

The benefits of close adherence to a Mediterranean diet were similar for people with and without the ApoE gene, meaning that the effects of diet on cognition are independent of genetic risk for Alzheimer’s disease.

Funding: The AREDS and AREDS2 studies were supported by the NEI Intramural Research Program and contracts NOI-EY-0-2127 (AREDS), HHS-N-260-2005-00007-C (AREDS2), and N01-EY-5-0007 (AREDS2). Additional research funds were provided by the NIH Office of Dietary Supplements, the National Center for Complementary and Integrative Health, the National Institute on Aging, the National Heart, Lung, and Blood Institute, and the National Institute of Neurological Disorders and Stroke. The AREDS trial is registered at http://www.ClinicalTrials.gov as NCT00594672. AREDS2 is registered as NCT00345176. The studies took place at the NIH Clinical Center.


Mediterranean Diet (MeDi) and AD Prevention

The Mediterranean diet (MeDi) would appear to be promising for AD prevention, including the earlier predementia stages. Indeed, the MeDi diet, based on traditional eating habits in Greece, Southern Italy, and other Mediterranean regions, albeit with regional differences, is characterized by high consumption of fruits and vegetables, cereals, legumes, olive oil, nuts, and seeds as the major source of fats, moderate consumption of fish, low to moderate consumption of dairy products and alcohol (wine), and low intake of red and processed meats (see Table 1).

It can be considered a nutritional model for healthy dietary habits since it contains all the essential nutrients including monounsaturated fatty acids (mainly in olive oil), polyunsaturated fatty acids (in fatty fish), antioxidants (e.g., allium sulphur compounds, anthocyanins, beta-carotene-flavonoids, catechins, carotenoids, indoles, or lutein), vitamins (A, B1, 6, 9, 12, D, and E), and minerals (magnesium, potassium, calcium, iodine, zinc, and selenium) [19].

Growing evidence indicates the neuroprotective potential of the MeDi, thus supporting the rationale that adherence to this dietary pattern can be a preventative approach towards reducing the risk of cognitive decline, mild cognitive impairment (MCI), and AD [20, 21].

Table 1

Type and frequency of consumption of foods of the various dietary patterns having a role in AD prevention.

Dietary patternCharacteristics
Moderate-to-high consumptionLow consumption
Mediterranean diet (MeDi)Whole-grain cereals (1-2 s every main meal)
Vegetables (≥2 s/every main meal)
Fruits (1-2 s/every main meal)
Olive oil (every main meal)
Olives/nuts/seeds (1-2 s/every day)
Low-fat diaries (2 s/every day)
Herbs/spices/garlic/onions (every day)
Eggs (2-4 s/week)
White meat (2 s/week)
Fish/seafood (≥2 s/week)
Potatoes (≤3 s/week)
Legumes (≥2 s/week)
(Red) wine
Added salt
Red meat (<2 s/week)
Processed meat (<1 s/week)
Sweets (≤2 s/week)
Dietary Approaches to Stop Hypertension (DASH)Whole-grain products (every day)
Vegetables (every day)
Fruits (every day)
Diary (moderate-to-high consumption)
Poultry (2 s/week)
Fish/seafood (1-2 s/week)
Legumes (2 s/week)
Saturated fats
Total fats
Salt (sodium)
Sweetened beverages
Red and processed meats
Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND)Green leafy vegetables (≥6 s/week)
Other vegetables (≥1 s/day)
Nuts (≥5 s/week)
Berries (≥2 s/week)
Beans (≥3 s/week)
Whole grains (≥3 s/day)
Fish (≥1 s/week)
Poultry (≥2 s/week)
Olive oil (primary oil used)
(Red) wine (1 glass/day)
Red meats (<4 s/week)
Butter and stick margarines
Cheese (<1 s/week)
Pastries and sweets (<5 s/week)
Fried or fast food (<1 s/week)

Mediterranean Diet and Brain Imaging

AD is a neurodegenerative disease characterized by typical changes in the brain that can be detected by a variety of imaging modalities, including structural and functional Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET).

In recent years, cross-sectional and longitudinal studies have shown the relationship between lifestyle and dietary habits and the morphological, structural, functional, and metabolic modifications of the brain regions that undergo neurodegeneration in the preclinical and clinical phases of AD.

Mediterranean Diet and Structural Brain Modifications

Growing evidence, derived mainly from MRI studies, suggests an association between higher MeDi adherence and preservation of brain structures, in particular in the so-called “Regions-of-Interest” (ROIs) which are vulnerable to the neurodegenerative changes typical of AD.

Higher MeDi adherence was associated with a significantly greater thickness of 3 ROIs (orbitofrontal cortex, entorhinal cortex, and posterior cingulate cortex of the left hemisphere) in a cross-sectional study performed on an American population of cognitively normal middle-aged participants [49].

Similar findings were reported by two other cross-sectional American studies in which the greatest benefit in terms of brain structure preservation was attributed to the higher intake of fish and legumes and lower intake of meat [50, 51].

More recently, Karstens et al. found that higher adherence to the Mediterranean pattern was associated with better learning and memory performance and larger bilateral dentate gyrus volumes after adjusting for a number of confounding factors [52].

Conversely, several longitudinal studies reported a negative effect on brain structures related to lower adherence to the MeDi [53] or adherence to an unhealthy Western dietary pattern [54], while a Swedish longitudinal study including 194 cognitively healthy elderly individuals found no association between the total MeDi score and the brain volumes perhaps due to the intrinsic limitations of the study design [55].

In conclusion, gray matter atrophy and reduced cortical thickness in the medial temporal lobe are a typical early feature of AD, and the association of MeDi adherence with greater gray matter volumes in AD regions may indicate some direct involvement of this type of dietary pattern in preventing or slowing the neurodegeneration and the consequent neuronal loss that is typical of this disease. More recently, Pelletier and colleagues reported a positive association between higher MeDi

adherence and a general pattern of preserved white matter microstructure with no relation to gray matter volumes, suggestive of alternative mechanisms partly independent of AD-related neurodegeneration, possibly including vascular pathways [56]. The beneficial effect of the MeDi on vascular risk factors (e.g., lipid profile, blood pressure, insulin resistance, adiposity, inflammation, and oxidative stress) is in fact well established [57–60].

2.3.2. Mediterranean Diet and Functional Brain Modifications
The AD brain is characterized by several metabolic changes that can also be found in other neurodegenerative diseases and in normally aging brains and represent nonspecific biomarkers of impairment of neuronal activity and synaptic transmission.

These metabolic and functional modifications can be detected by PET, in particular, fluorodeoxyglucose- (FDG-) PET and Pittsburgh Compound B- (PiB-) PET which allow us to evaluate changes in cerebral glucose metabolism (an indicator of neuronal network activity) and the degree of beta-amyloid (Aβ) deposition in brain regions known to be involved in AD. Studies concerning the association between MeDi adherence (and in general, adherence to a healthy dietary pattern) and functional neuroimaging outcomes are limited.

Two cross-sectional studies in the American population found an association between higher adherence to a MeDi pattern and lower 11C-PiB PET scan measurements of Aβ deposition as well as higher glucose metabolism as observed by FDG-PET scans [61, 62].

Higher MeDi adherence was also associated with reduced cerebral Aβ accumulation over time (up to 3 years) in a longitudinal study performed by Rainey-Smith et al. on older Australian adults classified as “Aβ accumulators” and thus considered to be on the way to AD [63]. However, the association between the Mediterranean dietary pattern and amyloid deposition or cortical thickness has not been confirmed in all reported studies.

In a longitudinal study that involved 70 middle-aged participants living in New York, lower adherence to a Mediterranean-style diet was associated with faster decline in glucose metabolism in the posterior cingulate cortex (an early site of cerebral glucose utilization decline in AD and a well-established predictor of the progression from mild cognitive impairment to AD) and marginally in the frontal cortex, although without any significant changes in amyloid deposition or cortical thickness [64].

In conclusion, the neuroprotective effects of the MeDi may also lie in its ability to preserve brain metabolic activity and glucose metabolism in key brain regions for AD.


Source:
NIH/NEI

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