Consuming a Mediterranean diet can significantly reduce Alzheimer's Disease (AD) risk, but not necessarily through vascular mediation, a study suggests.

Researchers at Columbia University in New York found individuals who followed a Mediterranean diet reduced their AD risk by up to 68% compared with those who did not adhere to this diet, which is rich in fruits, vegetables, legumes, cereals, and fish and low in meat and dairy products.

"This study confirms our previous research and has strengthened our confidence that adherence to the Mediterranean diet is associated with protective effect in Alzheimer's disease," the study's principal investigator Nikolaos Scarmeas, MD, told Medscape.

The study is published in the October 9 Early Release issue of the Archives of Neurology.

Previously the Mediterranean diet has been associated with lower risk for several forms of cancer, obesity, dyslipidemia, hypertension, abnormal glucose metabolism, coronary heart disease, and overall mortality.

However, said Dr. Scarmeas, the investigators' previous article, a prospective study published in the June 2006 issue of the Annals of Neurology, was the first of its kind to look at the diet's potential effect on neurologic diseases. The study found higher adherence to the principles of the Mediterranean diet at baseline evaluation was associated with a significantly lower risk for developing AD at follow-up.

"We wanted to see whether we could confirm these results in a different AD population," Dr. Scarmeas said.

Higher Adherence Equals Lower Risk

The current case-control study included 194 patients with known AD and 1790 individuals without dementia from the Washington Heights–Inwood Columbia Aging Project (WHICAP).

The main predictor of AD status was adherence to the principles of the Mediterranean diet during the past year. This was determined using a 0- to 9-point scale, with higher scores indicating greater adherence.

"We know from our previous research that Mediterranean diet adherence is stable over time, so that irrespective of whether patients remain cognitively healthy, their Mediterranean diet adherence remains more or less the same," said Dr. Scarmeas.

Subjects were divided into tertiles according to their dietary adherence scores. After adjusting for age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index, the researchers found subjects with the highest adherence had the lowest AD risk.

Furthermore, the authors report that each additional unit on subjects' scores was associated with 19% to 24% decreased risk of developing AD.

Table. Adjusted Risk of AD According to Mediterranean Diet Adherence Scores by Tertile*

Tertile	Odds Ratio	95% CI
Low	1	(Reference)
Middle	0.47	(0.29 - 0.76)
High	0.32	(0.17 - 0.59)

*AD indicates Alzheimer's Disease; and CI, confidence interval. All values are adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, comorbidity index, and body mass index.
Source: Arch Neurol. Published online October 9, 2006.

Dr. Scarmeas noted the inclusion of vascular variables, such as stroke, diabetes mellitus, hypertension, heart disease, and total cholesterol, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol levels did not change the magnitude of the association.

Possible Mechanisms

"We wanted to investigate the potential mechanism by which this diet might mediate AD risk. There is substantial evidence to show it protects against diabetes, abnormal lipid profiles, heart disease, and so forth and so one potential mechanism was through vascular medication. So we investigated this possibility but it turned out not to be the case," Dr. Scarmeas said.

This finding, Dr, Scarmeas added, suggests 1 of 2 possibilities. "It is either due to measurement error. In other words, the way we measured cardiovascular and cerebrovascular risk factors is not accurate enough, or the diet is working through different pathways to reduce Alzheimer's risk possibly by reducing inflammation or oxidative stress in the brain," Dr. Scarmeas said.

These, and other issues Dr. Scarmeas said, will be the focus of future research. In the meantime, however, although there is a need for more studies, Dr. Scarmeas said it is probably prudent to recommend the Mediterranean diet to patients as a possible way of reducing their AD risk.

"We have not reached yet the level of evidence to definitively recommend this diet for the prevention of Alzheimer's Disease. There have been no clinical trials and other groups have not replicated these results. On the other hand, considering the positive results of our two studies, and taking into account that the [Mediterranean] diet has been shown to be beneficial for many other diseases, it would make sense for patients to adopt it as early as possible," Dr. Scarmeas said.

Arch Neurol. Published online October 9, 2006.

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

• Describe the association between the Mediterranean diet and risk for AD.
• Describe the dose-response relationship between adherence to the Mediterranean diet and risk for AD.

Clinical Context

According to the current authors, there is a paucity of data on the effect of composite dietary patterns on the risk for AD. The Mediterranean diet consists of foods with antioxidant properties, such as olive oil, wine, fruits and vegetables, vitamins C and E, and carotenoids, and may protect against oxidative stressors and inflammation. The Mediterranean diet has been associated with lower risk of several forms of cancer, obesity, hypertension, dyslipidemia, coronary heart disease, and overall mortality. The current authors recently demonstrated that higher adherence to a Mediterranean diet was associated with lower incidence of AD in those without AD at baseline in a study published in the June 2006 issue of the Annals of Neurology.

The authors' current study is a prospective case control study nested within a community-based cohort in one city to examine whether high adherence to the Mediterranean diet predicted AD status among patients with AD and those who did not have dementia at baseline.

Study Highlights

• 2 multiethnic cohorts living in 3 census tracts in 1 city received baseline history, physical and neurologic examination, and global summary score on the Clinical Dementia Rating scale, including tests of memory, orientation, abstract thinking, and construction.
• The diagnosis of dementia was made by Diagnostic and Statistical Manual of Mental Disorders Revised Third Edition criteria and the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer Disease, and Related Disorders Association criteria were used to classify dementia.
• Patients with and without dementia at baseline were followed up, and their dietary pattern was assessed.
• Patients who did not have dementia at baseline but developed dementia during follow-up, those who had a Clinical Dementia Rating score higher than 0, and those with dementia but had either a non-AD diagnosis or Clinical Dementia Rating higher than 1 were excluded from analysis.
• Dietary data on average consumption for the past year were obtained using the 61-item Willet's semiquantitative questionnaire.
• The Mediterranean diet score was computed using derived residuals of daily gram intake of 7 categories of food- and sex-specific medians as cutoffs. The scores for each category were added (range, 0 - 9), with higher score indicating higher adherence to the Mediterranean diet.
• The 7 food categories representing the components of the Mediterranean diet were fruits, vegetables, dairy, meat, legumes, cereals, and fish.
• The diagnosis of comorbidities, such as stroke, diabetes, and hypertension, was verified with family and patients, and fasting laboratory tests were performed.
• Mean age was 76 years, 30% were male, 35% were white, 33% were black, 30% were Hispanic, 10% smoked, 7% had stroke, and 19% had diabetes mellitus.
• There were 194 patients with and 1790 without dementia at baseline.
• Reported Mediterranean diet scores were stable over time.
• Follow-up occurred for a mean of 8.1 years.
• 89 patients who did not have dementia at baseline developed AD during follow-up.
• Compared with controls without dementia, those with AD at baseline were older, less educated, and had lower body mass indexes.
• There were fewer men, more Hispanics, and fewer whites with AD at baseline. History of stroke was more common in those with AD.
• There was no association between Mediterranean diet score and age, sex, education, apolipoprotein E genotype, medical comorbidity index, body mass index, and any vascular variables.
• Higher adherence to the Mediterranean diet was associated with lower risk for AD (odds ratio, 0.76; P < .01).
• Compared with patients in the lowest tertile of adherence, those in the middle tertile had an odds ratio of 0.47, and those in the highest tertile had an odds ratio of 0.32 for AD (P for trend < .001), suggesting a dose-response effect.
• Each additional unit of the Mediterranean diet score was linked with a 19% to 24% lower risk of developing AD.
• When stroke was removed as a variable, the outcomes remained the same.
• Odds ratio did not change when accounting for vascular variables.