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Monday, March 30, 2015

The Mediterranean-DASH Intervention for Neurodegenerative Delay – The MIND Diet and AD

Dear Readers,

Information on the role of diet and physical activity to cardiovascular health has been reported in the literature for many years. Recently, the focus has shifted to brain health; what is the role of nutrition to brain health? Are there certain foods that would prevent cognitive decline or Alzheimer’s disease (AD) or enhance cognition? A recent paper by Morris et al. sought to examine the relationship between diet and developing AD, from a well established longitudinal study of persons in Chicago participating in the Memory and Aging Project (MAP).

The Memory and Aging Project is a cohort study of people aged 65 years and older living in retirement communities and senior public housing units in the Chicago area. The cohort study began in 1997 and includes annual cognitive testing and clinical neurological examinations. From 2004 - February 2013, the MAP study participants were invited to complete food frequency questionnaires. Over the course of the diet study, 1,545 older adults enrolled in the MAP study and 1,068 completed the dietary questionnaires. A total of 923 had at least two neuropsychological assessments and were clinically determined not to have AD at baseline. All data derived was based on this group of people. The food questionnaire asked participants to report usual frequency of intake over the previous 12 months of 144 food items. Nutrient levels and total energy for each food item were based either on portion sizes (e.g. slice of bread) or according to age- and sex-specific portion sizes from national dietary surveys.

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet score has 15 dietary components including 10 brain healthy food groups (green leafy vegetables, other vegetables, nuts, berries, beans, whole grains, fish, poultry, olive oil and wine) and five unhealthy food groups (red meats, butter and stick margarine, cheese, pastries and sweets, and fried/fast food) (1) . The total MIND diet score was determined by summing up all 15 of the component scores. The DASH diet scoring, was based on seven food groups and three dietary components (total fat, saturated fat and sodium).(2) The Mediterranean Diet Score includes 11 dietary components, and was computed based on scoring as established scoring scales (3). Over the course of 4.5 years, a total of 144 people developed AD. The MIND diet score was linearly associated with a lower risk of developing AD - people with the top MIND diet scores had a 53% reduction in the rate of developing AD compared with participants with the lowest. Even those participants in the middle range of the MIND diet scores had a statistically significant 35% reduction in AD rate compared with those with the highest scores. Consider how this compares to results from two other diets, the Mediterranean and DASH. Only the highest levels of the Mediterranean and DASH diet scores were significantly associated with reduction of incident AD. (54% reduction in AD for Mediterranean diet and 39% reduction for the DASH diet).

Interestingly, the MIND diet and relationship to developing AD was not modified by age, sex, education, physical activity, obesity, low BMI, or histories of stroke, diabetes, or hypertension. Thus this diet appears to be a more “realistic” type of diet that many adults can apply and derive benefits. Future studies in larger community based populations and populations that are racially / ethnically diverse are needed to examine whether this diet offers the same beneficial effects.

Want to read more? Here are three articles you can review to learn about the diet, nutrition and Alzheimer’s Disease.

1) Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimer’s Dement. 2015 Feb 11.S1552-5260(15)

2) Folsom AR, Parker ED, Harnack LJ. Degree of concordance with DASH diet guidelines and incidence of hypertension and fatal cardiovascular disease. Am J Hypertens 2007; 20:225-232.

3) Panagiotakos DB, Pitsavos C, Arvaniti F, Stefanadis C. Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults; the accuracy of the MedDietScore. Prev Med 2007; 44:335-340.

Thanks for reading.

Neelum T. Aggarwal, MD
Steering Committee Member, ADCS
Rush Alzheimer’s Disease Center
Rush Institute for Aging
Chicago, IL

Author: Neelum Aggarwal MD at 2:00 PM 0 Comments

Monday, March 16, 2015

Stem Cells Elucidate Genetic Mechanism for Protection from Alzheimer’s

Dear Readers,

Genes come in different versions or variants. That is, the gene for eye color may be slightly different from one person to another (green, blue, etc). These variations typically impart differences in the functions of the proteins that are encoded by their genes (type of pigment in the iris). In the last few years, many gene variants have been discovered that are considered risk factors for AD. One of these is the gene SORL1, which encodes a protein called sortilin-related receptor-1 that is highly enriched in neurons. Previous studies have shown that certain variants of the SORL1 gene confer some protection from AD, while other variants are associated with about a 30 percent higher likelihood of developing the disease.

In a recent study led by Larry Goldstein at UCSD, researchers took skin cells from 13 people, seven of whom had AD and six of whom were healthy control subjects, and reprogrammed the skin cells into stem cells. These stem cells were coaxed to differentiate into neurons, and the neurons were cultured and then treated with a Brain Derived Neurotrophic Factor (BDNF), an endogenous protein that helps keep neurons healthy. BDNF is in fact being studied as a potential therapy for AD.

The researchers found that neurons carrying the disease-protective SORL1 variants responded to the BDNF therapy by reducing their baseline rate of beta amyloid peptide production by an average 20 percent. But the neurons carrying the risk variants of the SORL1 gene showed no change in beta amyloid production. These results demonstrate that BDNF reduces beta-amyloid production in neurons by boosting the activity of SORL1 and that the SORL1 should be of a certain variety in order to be responsive in the first place.

This kind of stem cell study also further supports the idea that levels of beta-amyloid production are important for the development of AD. It also clarifies the mechanism by which variants of SORL1 impart risk for or protection against AD. And finally, this type of work allows researchers to identify exactly how a person’s genetic background might determine their response to potential treatments, in this case to BDNF.

Thanks for reading,

Michael Rafii, MD, PhD
Director, Memory Disorders Clinic
Medical Core Director
Alzheimer’s Disease Cooperative Study
University of California San Diego
Author: Michael Rafii MD,PhD at 12:03 PM 0 Comments

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The Alzheimer's Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego. The ADCS is a major initiative for Alzheimer's disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Division of Neuroscience's effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer's Disease Prevention Initiative.

The ADCS was developed in response to a perceived need to advance research in the development of drugs that might be useful for treating patients with Alzheimer's disease (AD), particularly drugs that might not be developed by industry.