Mediterranean Diet

Mediterranean Diet and Alzheimer's

The Mediterranean diet also been shown to have positive effect on Alzheimer’s.  Even though Italy and Spain are on the Mediterranean, the mediterranean diet is not pasta, tapas and pizza.  The Mediterranean diet is very specific.  It is defined as the diet typically eaten in Crete between in the 1950s and 1960s.  The diet is mostly vegetarian and consists of fruits, vegetables, beans, nuts, seeds, and unrefined cereals.  The diet has high levels of antioxidants and olive oil is the primary source of fat.  The preferred animal protein is fish or other seafood.  Meat and dairy intake is limited which contributes to the low levels of saturated fat in the diet and higher levels of mono and polyunsaturated fat.  Emphasis is on healthy fats, such as olive oil, nuts, avocado, and fish. Beverage intake is mostly water with moderate red wine with meals.1,2        

For many decades, the Mediterranean Diet has been known to reduce the risk of many age related diseases such as cardiovascular disease, metabolic disorders, cerebrovascular disorders, and cancer.  It also has a positive effect on mortality.  Recently, the benefits of the Mediterranean Diet are now being recognized as a way to combat Alzheimer’s disease.3 

Alzheimer's and Mediterranean Diet Studies

Many observational studies have shown a positive effect of the Mediterranean Diet on cognition.  However, the most important way to measure clinical outcomes is by randomized clinical trials, of which there are four: the Predimed-Navarra Study, the Predimed Study, the Medley Study, and the Nu-Age Study.4  

In the two Predimed studies, cognitively healthy subjects, but at risk for cardiovascular disease, volunteered to take part in multi-year studies.  Participants were randomized into three groups.  A group who ate the mediterranean diet supplemented with extra virgin olive oil (1 liter per week), a group who ate the mediterranean diet supplemented with mixed nuts (30 grams per day) and a control group who were advised to reduce dietary fat.  In the Predimed study, cognitive tests scores were standardized into three composite scores for different types of cognitive function: memory, frontal functions (measuring attention, cognitive flexibility and working memory) and global cognition which was defined as a composite of all the neurological tests.  After a four year period, the group eating the Mediterranean Diet supplemented with olive oil had improved cognition in every cognitive test compared to the initial testing when the study began.  The group eating the Mediterranean Diet supplemented with nuts had improved cognition in two out of three cognitive functional areas.  The control diet had decreased cognitive scores in every cognitive functional area.  In addition, the study found that the benefits of the Mediterranean Diet were independent of Apoe4 status and would therefore benefit Apoe4 carriers.5,6 

The Predimed-Navarra study did not have an initial cognitive test at the start of the study but after six and a half years the groups on the Mediterranean Diet supplemented with nut or olive oil scored better on cognitive tests compared to the control group.  Unfortunately, in 2018 it was determined that the randomization procedure for the Predimed studies might not have been followed in one of the centers participating in the study and therefore the study was not truly randomized.7,8   

The MedLey study was the first study to test the effectiveness of the Mediterranean diet outside of the Mediterranean region.  The MedLey study randomly assigned 137 healthy older men and women to the Mediterranean diet or their normal diet which was considered the control diet.  The study lasted six months, but unfortunately the MedLey study did not find that the Mediterranean diet improved cognition.9    

The Nu-Age randomized clinical trial included 1,279 healthy older people that were randomized into a Mediterranean diet group and a group that continued to eat their normal diet.  Cognition was tested at the beginning of the study and after one year, but unfortunately there was no significant difference between groups.  However, more adherence to the Mediterranean Diet did translate into a better cognition.3     

Apoe4 Carriers and Mediterranean Diet

Even though the Predimed study stated that the positive results of the Mediterranean diet were independent of Apoe4 status, other studies have shown that the Mediterranean diet benefits Apoe4 non-carriers more than it does Apoe4 carriers.  One way to screen people with cognitive issues such as Alzheimer’s disease is the clock drawing test.  A person with poor cognition will draw a very abnormal looking clock while someone with normal cognition will draw a normal looking clock.  One study showed that Apoe4 non-carriers on the Mediterranean diet improved their clock drawing ability while Apoe4 carriers showed no improvement on the clock drawing test.  However, both Apoe4 carrier and noncarriers improved cognition as determined by additional testing.10,11     

Other Mediterranean Diet and Alzheimer's Genetic Factors

Other Alzheimer’s genetic risk factors also influenced the effectiveness of the Mediterranean diet.  People with the T allele for SNP rs11136000 on the CLU gene was shown to have improved their clock drawing capabilities after the Mediterranean diet.  The same was true for the SNP rs3818361 CR gene variant with subjects without the A allele and the PICALM gene SNP rs3851179 with at least one copy of the T allele.  This data shows that genetics, diet and cognition are very much interrelated.  A diet that might work for one person may not work for another because of their genetic make-up is different.  If you are interested in the Mediterranean diet, I would recommend looking into these SNPs before moving forward.10,11      

Additional Mediterranean Diet Information

Some people have pointed out that the Mediterranean Diet is not just a diet but a lifestyle change.  Crete and much of the Mediterranean has a cultural tendency to eat in larger groups with families and friends.  Being social should be an important part of your fight against Alzheimer’s and whatever diet you choose, try to share more meals with other people.  This website has an entire section dedicated to this concept (see Socializing), but for now, be like the people in Crete. Never eat alone.    

One characteristic of the Mediterranean Diet is consumption of red wine.  Red wine has been shown to have positive benefits for a variety of health issues, most famously for cardiovascular disease.  But before adding red wine to your dinner tonight, read the beverages section of this website and you’ll see why alcohol may not be a good choice for some people.  

Mediterranean Diet References on this Page:

  1. Yngve A. A Historical Perspective of the Understanding of the Link between Diet and Coronary Heart Disease. Am J Lifestyle Med. 2009;3(1 Suppl.):35S-38S. doi: 10.1177/1559827609334887. PMID: 20046857; PMCID: PMC2790142.
  2. https://www.hsph.harvard.edu/nutritionsource/healthy-weight/diet-reviews/mediterranean-diet/
  3. Marseglia A, Xu W, Fratiglioni L, Fabbri C, Berendsen AAM, Bialecka-Debek A, Jennings A, Gillings R, Meunier N, Caumon E, Fairweather-Tait S, Pietruszka B, De Groot LCPGM, Santoro A, Franceschi C. Effect of the NU-AGE Diet on Cognitive Functioning in Older Adults: A Randomized Controlled Trial. Front Physiol. 2018 Apr 4;9:349. doi: 10.3389/fphys.2018.00349. PMID: 29670545; PMCID: PMC5893841.
  4. Vinciguerra F, Graziano M, Hagnäs M, Frittitta L, Tumminia A. Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review. Nutrients. 2020 Apr 8;12(4):1019. doi: 10.3390/nu12041019. PMID: 32276339; PMCID: PMC7231139.
  5. Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Martínez-González MÁ, Martínez-Lapiscina EH, Fitó M, Pérez-Heras A, Salas-Salvadó J, Estruch R, Ros E. Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA Intern Med. 2015 Jul;175(7):1094-1103. doi: 10.1001/jamainternmed.2015.1668. Erratum in: JAMA Intern Med. 2018 Dec 1;178(12):1731-1732. PMID: 25961184.
  6. Martínez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvadó J, San Julián B, Sanchez-Tainta A, Ros E, Valls-Pedret C, Martinez-Gonzalez MÁ. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013 Dec;84(12):1318-25. doi: 10.1136/jnnp-2012-304792. Epub 2013 May 13. PMID: 23670794.
  7. Martínez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvadó J, San Julián B, Sanchez-Tainta A, Ros E, Valls-Pedret C, Martinez-Gonzalez MÁ. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013 Dec;84(12):1318-25. doi: 10.1136/jnnp-2012-304792. Epub 2013 May 13. PMID: 23670794.
  8. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Fitó M, Gea A, Hernán MA, Martínez-González MA; PREDIMED Study Investigators. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018 Jun 21;378(25):e34. doi: 10.1056/NEJMoa1800389. Epub 2018 Jun 13. PMID: 29897866.
  9.  Knight A, Bryan J, Wilson C, Hodgson JM, Davis CR, Murphy KJ. The Mediterranean Diet and Cognitive Function among Healthy Older Adults in a 6-Month Randomised Controlled Trial: The MedLey Study. Nutrients. 2016 Sep 20;8(9):579. doi: 10.3390/nu8090579. PMID: 27657119; PMCID: PMC5037563.
  10.  Berkowitz CL, Mosconi L, Rahman A, Scheyer O, Hristov H, Isaacson RS. Clinical Application of APOE in Alzheimer’s Prevention: A Precision Medicine Approach. J Prev Alzheimers Dis. 2018;5(4):245-252. doi: 10.14283/jpad.2018.35. PMID: 30298183; PMCID: PMC6188641.
  11.  Martínez-Lapiscina EH, Galbete C, Corella D, Toledo E, Buil-Cosiales P, Salas-Salvado J, Ros E, Martinez-Gonzalez MA. Genotype patterns at CLU, CR1, PICALM and APOE, cognition and Mediterranean diet: the PREDIMED-NAVARRA trial. Genes Nutr. 2014 May;9(3):393. doi: 10.1007/s12263-014-0393-7. Epub 2014 Mar 19. PMID: 24643340; PMCID: PMC4026432.

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