Tag Archives: dementia

Right Diet Preserves Brain Function and Size

mp9004223691.jpg  Neurology last year reported that the proper diet seems to help prevent age-related brain shrinkage and cognitive decline.

From the press release:

People with diets high in several vitamins or in omega 3 fatty acids are less likely to have the brain shrinkage associated with Alzheimer’s disease than people whose diets are not high in those nutrients, according to a new study published in the December 28, 2011, online issue of Neurology, the medical journal of the American Academy of Neurology.

Those with diets high in omega 3 fatty acids and in vitamins C, D, E and the B vitamins also had higher scores on mental thinking tests than people with diets low in those nutrients. These omega 3 fatty acids and vitamin D are primarily found in fish. The B vitamins and antioxidants C and E are primarily found in fruits and vegetables.

So the dietary pattern linked to preservation of brain size and function in this study is: high omega-3 fatty acids and vitamins B, C, D, and E. I don’t know if study participants were getting these nutrients from supplements or from food or a combination. (I haven’t read the full article.)

Note that the time-honored Mediterranean diet is also associated with lower rates of dementia and slower rate of age-related mental decline.

I previously reported that a supplement cocktail of three B vitamins slowed the rate of brain shrinkage

Steve Parker, M.D.

Reference: Bowman, G.L., et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology. doi: 10.1212/WNL.0b013e3182436598

h/t to Randall Parker at FuturePundit

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Filed under Dementia, Health Benefits, Mediterranean Diet

Nasal Insulin Slows Dementia?

 

Insulin administered via the nasal passages slowed or stabilized mental functioning and functional abilities in a pilot study of people with Alzheimer disease and mild cognitive impairment, according to Seattle-based investigators.

As you probably know, dementia is a huge problem for our aging population, and Alzheimers is the most common form of dementia.  The Mediterranean diet is associated with lower risk of mild cognitive impairment and has long been linked to lower risk of dementia as well as slower mental decline in existing Alzheimer dementia patients.  The Mediterranean diet also seems to prolong life in Alzheimer patients.  So I’m always interested in ways to prevent and treat Alzheimers.  Mild cognitive impairment is often a precursor to Alzhiemer disease.

Methodology

The study involved 104 non-diabetic participants with Alzheimer disease (40) or amnestic mild cognitive impairment (64).  They were randomly assigned to one of three groups: placebo (control group), nasal insulin 20 IU twice daily, or nasal insulin 40 IU twice daily. 

Insulin was delivered through a ViaNase device which releases the insulin in to a chamber covering the nose; the participant breathes regularly for two minutes to pick up the dose.  This insulin goes directly to the central nervous system without affecting blood insulin levels or blood sugar levels.

Mental and functional abilities (for example, activities of daily living) were measured at baseline, then again 2, 4, and six months later.  Some of the participants (23) underwent lumbar puncture (for dementia biomarker analysis) and PET brain scans (18).

Comments

This was a well-designed pilot study.

Nasal insulin was well-tolerated.  It’s not commercially available in the U.S.

ResearchBlogging.orgRegarding the placebo group, I was surprised that the researchers could document mental and functional deterioration over this relatively short-term study (4–6 months).  I’m impressed with the need to treat age-related cognitive decline early and aggressively, when we have something that works.

How would nasal insulin work?  We don’t know for sure, but it seems to relate to insulin’s effect on

  • the ability of neurons (brain cells) to communicate with each other through synapses
  • modulaton of blood sugar metabolism in the hippocampus and other brain areas
  • facilitation of memory
  • ß-amyloid peptide

In case you’re wondering, standard subcutaneous injections of insulin can’t be used in studies like this because of the risk of low blood sugar.

I agree wholeheartedly with study authors that “these promising results provide an impetus for longer-term trials of intranasal insulin therapy in adults with amnestic mild cognitive impairment or Alzheimers disease.”

Psychiatrist Emily Deans blogged about this study at Evolutionary Psychiatry September 21, 2001.  Please see her cogent remarks.

Steve Parker, M.D.

Reference:  Craft, S., Baker, L., Montine, T., Minoshima, S., Watson, G., Claxton, A., Arbuckle, M., Callaghan, M., Tsai, E., Plymate, S., Green, P., Leverenz, J., Cross, D., & Gerton, B. (2011). Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial Archives of Neurology DOI: 10.1001/archneurol.2011.233

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Filed under Dementia

Mediterranean Diet Linked to Brain Preservation

 The Mediterranean diet slowed age-related mental decline in elderly Chicago residents, according to researchers at Rush University Medical Center.  The investigators noted that a Manhattan population following the Mediterranean diet also showed slower mental decline and lower rates of Alzheimers dementia.

Over 3,000 study participants (2,280 blacks, 1,510 whites) were studied for an average of eight years.  Food consumption was determined by questionnaires, and mental function was tested every three years.  Adherence to the Mediterranean diet was judged according to a Mediterranean diet score developed by Panagiotakis, et al.

The greater the adherence to the Greek-style Mediterranean diet, the lower the rate of mental decline over the course of the study.

Mental decline to some extent is a normal part of aging.  If we can avoid it or lessen it’s impact, why not?  A couple ways to do that are regular exercise and the Mediterranean diet.

Would a low-carb Mediterranean diet work just as well or better?  Nobody knows yet.

Steve Parker, M.D.

Reference:  Tangney, Christine, et al. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population.  American Journal of Clinical Nutrition, 2010.  doi 10.3945/ajcn.110.007369

 

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Filed under Health Benefits, Mediterranean Diet

WHY Is the Mediterranean Diet So Healthy?

I’ve found that nearly everbody’s eyes glaze over if I try to explain how, physiologically, the Mediterranean diet promotes health and longevity.  Below are some of the boring details, for posterity’s sake, mostly from my 2007 book, The Advanced Mediterranean Diet: Lose Weight, Feel Better, Live Longer.

Many of the nutrient-disease associations I mention below are just that: associations, linkages, not hard proof of a benefit.  Available studies are often contradictory.  For instance, there may be 10 observational studies linking whole grain consumption with reduced deaths from heart disease, while three other studies find no association, or even suggest  higher death rates. (I’m making these numbers up.)  If you want hard proof, you’ll have to wait.  A long time.  Such is nutrition science.  Take it all with a grain of salt. 

Also note that the studies supporting my claims below are nearly all done in non-diabetic populations.

Coronary Heart Disease

Coronary heart disease, also known as coronary artery disease, is the No.1 cause of death in the world. It’s responsible for 40% of deaths in the United States and other industrialized Western countries. The Mediterranean diet is particularly suited to mitigating the ravages of coronary heart disease. Mediterranean diet cardiac benefits may be related to its high content of monounsaturated fat (in olive oil), folate, and antioxidants.

The predominant source of fat in the traditional Mediterranean diet is olive oil, which is rich in monounsaturated fatty acids. High intake of olive oil reduces blood levels of triglycerides, total cholesterol, and LDL (“bad”) cholesterol. HDL or “good” cho-lesterol is unaffected. Olive oil tends to lower blood pressure in hypertensive people. Monounsaturated fatty acids reduce cardiovascular risk substantially, particularly when they replace simple sugars and easily digestible starches. Monounsaturated fatty acids and olive oil may also reduce breast cancer risk. The cardioprotective (good for the heart) and cancer-reducing effects of olive oil may be partially explained by the oil’s polyphenolic compounds.
    
Nuts are another good source of monounsaturated fatty acids and polyunsaturated fatty acids, including some omega-3 polyunsaturated fatty acids. Nuts have been proven to be cardioprotective. They lower LDL and total cholesterol levels, while providing substantial fiber and numerous micronutrients, such as vitamin E, potassium, magnesium, and folic acid. Compared with those who never or rarely eat nuts, people who eat nuts five or more times per week have 30 to 50% less risk of a fatal heart attack. Lesser amounts of nuts are also cardioprotective, perhaps by reducing lethal heart rhythm dis-turbances. 
    
Another key component of the Mediterranean diet is fish. Fish are excellent sources of protein and are low in cholesterol. Fatty, cold-water fish are particularly good for us because of their omega-3 polyunsaturated fatty acids: eicosapentaenoic acid (EPA) and docosahexanaenoic acid (DHA). The other important omega-3 polyunsaturated fatty acid is alpha-linolenic acid (ALA), available in certain plants. Our bodies can convert ALA into EPA and DHA, but not very efficiently. Fish oil supplements, which are rich in EPA, lead to lower total cholesterol and triglyce-ride levels. Fish oil supplements have several properties that fight atherosclerosis (hardening of the arteries). In people who have already had a heart attack, the omega-3 polyunsaturated fatty acids have proven to dramatically reduce cardiac deaths, especially sudden death, and nonfatal heart attacks. So omega-3 polyunsaturated fatty acids are “cardioprotective.”

The first sign of underlying coronary heart disease in many people is simply sudden death from a heart attack (myocardial infarction) or heart rhythm disturbance. These unfortunate souls had hearts that were ticking time bombs. I have little doubt that a significant number of such deaths can be prevented by adequate intake of cold-water fatty fish. As a substitute for fish, fish oil supplements might be just at beneficial. The American Heart Association also recommends fish twice weekly for the general population, or fish oil supplements if whole fish isn’t feasible. Compared with fish oil capsules, whole fish are loaded with vitamins, minerals, and protein. The richest fish sources of omega-3 polyunsaturated fatty acids are albacore (white) tuna, salmon, sar-dines, trout, sea bass, sword-fish, herring, mackerel, anchovy, halibut, and pompano.
    
Cardioprotective omega-3 polyunsaturated fatty acids (mainly ALA) are also provided by plants, such as nuts and seeds, legumes, and vegetables. Rich sources of ALA include walnuts, butternuts, soy-beans, flaxseed, almonds, leeks, purslane, pinto beans, and wheat germ. Purslane is also one of the few plant sources of EPA. Several oils are also very high in ALA: flaxseed, canola, and soybean. Look for them in salad dressings, or try cooking with them.

Macular Degeneration

Omega-3 fatty acid and fish consumption may also be “eye-protective.” Eating fish one to three times per week apparently helps prevent age-related macular degeneration (AMD), the leading cause of blindness in people over 50 in the United States. While AMD has a significant hereditary component, onset and progression of AMD are affected by diet and lifestyle choices. For instance, smoking cigarettes definitely increases your risk of developing AMD. Other foods associated with lower risk of AMD are dark green leafy vegetables, orange and yellow vegetables and fruits: spinach, kale, collard greens, yellow corn, broccoli, sweet potatoes, squash, orange bell peppers, oranges, mangoes, apricots, peaches, honeydew melon, and papaya. Two unifying phytochemicals in this food list are lutein and zeaxanthin, which are also found in red grapes, kiwi fruit, lima beans, green beans, and green bell peppers. Increasing your intake of these foods as part of the Advanced Mediterranean Diet may well help preserve your vision as you age.      
    
Alzheimer’s Dementia
    
Another exciting potential benefit of fish consumption is prevention or delay of Alzheimer’s dementia. Several recent epidemiologic studies have suggested that intake of fish once or twice per week significantly reduces the risk of Alzheimer’s. Types of fish eaten were not specified. No one knows if fish oil capsules are equivalent. For now, I’m sticking with fatty cold-water fish, which I call my “brain food.”
    
Vitamin E supplements may slow the progression of established Alzheimer’s disease; clinical studies show either modest slowing of progression or no benefit. As a way to prevent Alzheimer’s, however, vitamin E supplements have been disappointing. On the other hand, high dietary vitamin E is associated with reduced risk of developing Alzheimer’s. Good sources of vitamin E include vegetable oils (especially sunflower and soybean), sunflower seeds, nuts, shrimp, fruits, and certain vegetables: sweet potatoes, asparagus, beans, broccoli, Brussels sprouts, carrots, okra, green peas, sweet peppers, spinach, and tomatoes. All of these are on your new diet. 

Wine

For centuries, the healthier populations in the Mediterranean region have enjoyed wine in light to moderate amounts, usually with meals. Epidemiologic studies there and in other parts of the world have associated reasonable alcohol consumption with prolonged lifespan, reduced coronary artery disease, diminished Alzheimer’s and other dementias, and possibly fewer strokes. Alcohol tends to increase HDL cholesterol, have an antiplatelet effect, and may reduce C-reactive protein, a marker of arterial inflammation. These effects would tend to reduce cardiovascular disease. Wine taken with meals provides antioxidant phytochemicals (polyphenols, procyanidins) which may protect against atherosclerosis and some cancers. 

What’s a “reasonable” amount of alcohol? An old medical school joke is that a “heavy drinker” is anyone who drinks more than the doctor does. Light to moderate alcohol consumption is generally consi-dered to be one or fewer drinks per day for a woman, two or fewer drinks per day for a man. One drink is 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of 80 proof distilled spirits (e.g., vodka, whiskey, gin). The optimal health-promoting type of alcohol is unclear. I tend to favor wine, a time-honored component of the Mediterranean diet. Red wine in particular is a rich source of resveratrol, which is thought to be a major contributor to the cardioprotective benefits associated with light to moderate alcohol consumption. Grape juice may be just as good—it’s too soon to tell.
    
I have no intention of overselling the benefits of alcohol. If you are considering habitual alcohol as a food, be aware that the health benefits are still somewhat debatable. Consumption of three or more alcoholic drinks per day is clearly associated with a higher risk of breast cancer in women. Even one or two drinks daily may slightly increase the risk. Folic acid supplementation might mitigate the risk. If you are a woman and breast cancer runs in your family, strongly consider abstinence. Be cautious if there are alcoholics in your family; you may have inherited the predisposition. If you take any medications or have chronic medical conditions, check with your personal physician first. For those drinking above light to mod-erate levels, alcohol is clearly perilous. Higher dosages can cause hypertension, liver disease, heart failure, certain cancers, and other medical problems. And psychosocial problems. And legal problems. And death. Heavy drinkers have higher rates of violent and accidental death. Alcoholism is often fatal. You should not drink alcohol if you:
            ■  have a history of alcohol abuse
                or alcoholism
            ■  have liver or pancreas disease
            ■  are pregnant or trying to become
                pregnant
            ■  may have the need to operate
                dangerous equipment or machinery,
                such as an automobile, while under
                the influence of alcohol
            ■  have a demonstrated inability to
                limit yourself to acceptable
                intake levels
            ■  have personal prohibitions due
                to religious, ethical, or other
                reasons. 
    
Cancer

Do you ever worry about cancer? You should. It’s the second leading cause of death. Over 500,000 people die from cancer each year in the United States. One third of people in the United States will develop cancer. Twenty percent of us will die from cancer. About half the deaths are from cancer of the lung, breast, and colon/rectum. Are you worried yet?

According to the American Cancer Society, one third of all cancer deaths can be attributed to diet and inadequate physical activity. So we have some control over our risk of developing cancer. High consumption of fruits and vegetables seems to protect against cancer of the lung, stomach, colon, rectum, oral cavity, and esophagus, although other studies dispute the protective linkage. Data on other cancers is limited or inconsistent. If you typically eat little or no fruits and vegetables, you can start today to cut your cancer risk by up to one half. Five servings of fresh fruits and vegetables a day seems to be the protective dose against cancer. Make it a life-long habit. The benefits accrue over time. Fruits and vegetables contain numerous phytochemicals thought to improve or maintain health, such as carotenoids (e.g., lycopene), lignans, phytosterols, sulfides, isothyocyanates, phenolic compounds (includ-ing flavonoids, resveratrol, phytoestrogens, anthocyanins, and tannins), protease inhibitors, capsaicin, vitamins, and minerals. 
   
In addition to cancer prevention properties, fruits and vegetables provide fiber, which is the part of plants resistant to digestion by our enzymes. The other source of fiber is grain products, especially whole grains. Liberal intake of fiber helps prevent constipation, diverticular disease, hemorrhoids, irritable bowel syndrome, and perhaps colon polyps. Soluble fiber helps control blood sugar levels in diabetics. It also reduces LDL cholesterol levels, thereby reducing risks of coronary heart disease. Whether or not related to fiber, high fruit and vegetable intake may reduce the risks of coronary heart disease and stroke. Legume consumption in particular has been associated with a 10 to 20% lower risk of coronary heart disease, with the effective dose being around four servings per week. 

Fiber and Whole Grains

Processed, refined grain products have much less fiber than do whole grains. For instance, white all-purpose enriched flour has only about one fourth the fiber of whole wheat flour. The milling process removes the bran, germ, and husk (chaff), leaving only the endosperm as the refined product, flour. Endosperm is mostly starch and 10–15% protein. Many nutrients are lost during processing. The germ is particularly rich in vitamins (especially B vitamins), polyunsaturated fatty acids, antioxidants, trace minerals, and phytochemicals. Phytochemicals protect us against certain chronic diseases. Bran is high in fiber and nutrients: B vitamins, iron, magnesium, copper, and zinc, to name a few. Enriched grain products are refined grains that have had some, but certainly not all, nutrients added back, typically iron, thiamin, niacin, riboflavin, and folate. Why not just eat the whole grain? Whole grain products retain nearly all the nutrients found in the original grain. Hence, they are more nutritious than refined and enriched grain products.
    
Liberal intake of high-fiber whole grain foods, as contrasted with refined grains, is linked to lower risk of death and lower incidence of coronary heart disease and type 2 diabetes mellitus. For existing diabetics, whole grain consumption can help im-prove blood sugar levels. Three servings of whole grains per day cut the risk of coronary heart disease by about 25 percent compared with those who rarely eat whole grains. Regular consumption of whole grains may also substantially reduce the risk of sev-eral forms of cancer.

Average adult fiber intake in the United States is 12 to 15 grams daily. Expert nutrition panels and the American Heart Association recommend 25 to 30 grams daily from whole grains, fruits, and vegetables.

The health benefits of the Mediterranean diet likely spring from synergy among multiple Mediteranean diet components, rather than from a single food group or one or a few food items. 

Steve Parker, M.D.

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Vitamins Slow Rate of Brain Shrinkage in Elderly

A cocktail of three common vitamins slowed the rate of brain shrinkage over two years  in elderly patients with mild cognitive impairment, according to researchers at the University of Oxford.  Less brain shrinkage should translate to better brain functioning.  People with diabetes need to know about this since diabetes is associated  with age-related cognitive impairment and dementia.  The dementia connection is debatable.

As a hospitalist, I see 10 or 20 brain scans every week.  A healthy 40-year-old brain nicely fills out the allotted space in the skull.  Most 70-year-old brains have an obvious degree of shrinkage.  Those with the most shrinkage typically have worse mental functioning, often diagnosed clinically as dementia, or its precursor, mild cognitive impairment (MCI).

The medical term for brain shrinkage is brain atrophy.  It reflects loss of brain cells or decrease in brain cell size.  I see A LOT of atrophied brains and impaired mental functioning—aka diminished cognition—in the elderly. 

Not everybody with atrophy has mental impairment; healthy brains slowly atrophy with age.  Alzheimer’s disease patients atrophy quickly; MCI patients atrophy at an intermediate rate.  MCI patients converting over the years to Alzheimer’s show a faster rate of atrophy.

Mild cognitive impairment affects 14 to 18% of those over age 70 (five million in the U.S.).  Half of these convert to Alzheimer’s disease or another dementia within five years.  We desperately need a way to prevent or slow that conversion.

That’s why I was excited to see a research report in which brain atrophy was slowed with three simple daily vitamins: folic acid 800 mcg, B12 500 mcg, and B6 20 mg.  (One Centrum vitamin, by comparison, provides folic acid 400 mcg, B12 6 mcg, and B6 2 mg).  The investigators will report later on whether the vitamins helped prevent mental decline.

These three vitamins are involved in homocysteine metabolism; they decrease blood levels of homocysteine.  Read elsewhere if you want the boring details. 

Methodology

Oxford area participants were at least 70 years of age and had mild cognitive impairment but not dementia.  Blood homocysteine levels were drawn periodically.  Participants were randomized to take either placebo (83 subjects) or the daily vitamins (85 subjects) for two years.  MRI scans were done periodically to determine brain volume.  Tests of mental functioning were done periodically.  More subjects were in the study at the outset but some dropped out and others didn’t have technically adequate MRI scans.

Results

After adjustment for age, the annual rate of brain atrophy was 30% less in the vitamin group compared to placebo.

For the placebo group, the rate of brain atrophy was clearly related to baseline homocysteine levels: higher homocysteine, faster atrophy.

Although the study was not powered to detect an effect of treatment on cognition (findings to be reported separately), in a post hoc analysis, we noted that final cognitive test scores were correlated to the rate of atrophy.

Atrophy appears to be a major determinant of cognitive decline in this population.

There were no significant safety issues and no differences in adverse events between the groups.

The vitamin group lowered homocysteine levels by 32% compared to placebo.

Reduction in brain shrinkage rate was best in those with a higher baseline homocysteine level (over 13 micromol/L); those with the lowest baseline levels (<9.5 micromol/L) showed no effect of vitamin therapy.  [In the U.S., 13% of those over 60 have concentrations over 13 micromol/L, whereas the median is 10 micromol/L.]

Comments

Although this is small study, I’m excited about the future clinical implications.  The results need to be replicated.  I can’t wait to hear from this group regarding the details of mental functioning tests.  If preservation of brain function or other practical benefits don’t accompany a slower rate of atrophy , it’s no use taking the vitamins.

A 2008 study found no clinical benefit with a similar vitamin mix in Alzheimer’s patients with mild to moderate disease.  In other words, the rate of mental decline was no different than the placebo group.  Average homocysteine level was 9.16 micromole/L and fell by 30% during the 18-month-long study.  Even those with the highest homocysteine levels showed no benefit.  Perhaps B vitamins need to be started much earlier in the disease process to be effective.

The time may come where we screen all 60-year-olds for above-average homocysteine levels, starting them on the vitamin cocktail.

One caveat, however.  Ten years ago doctors were quite excited about preventing heart disease events (e.g., heart attacks, cardiac deaths) and strokes in people with high homocysteine levels.  We knew that high levels were associated with cardiac events and strokes, and we knew the B vitamins would lower the blood levels.  We learned a couple years ago that B vitamin therapy actually didn’t help heart patients or those at high risk for heart disease.  Nor do the vitamins prevent strokes.  [If you’re a heart patient still taking Foltx, ask your cardiologist if it’s OK to stop it now.]

Steve Parker, M.D.

References: 

Smith, David, et al.  Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: A randomized controlled trial.  PLoS ONE 5(9): e1244.  doi: 10.1371/journal.pone.0012244  [published September 8, 2010]

Aisen, P.S., et al.  High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial.  Journal of the American Medical Association, 300 (2008): 1,774-1,783.

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THIS Is Why I Love the Mediterranean Diet

Italian researchers reviewed the medical/nutrition literature of the last three years and confirmed that the Mediterranean diet 1) reduces the risk of death, 2) reduces  heart disease illness and death, 3) cuts the risk of getting or dying from cancer, and 4) diminishes the odds of developing dementia, Parkinsons disease, stroke, and mild cognitive impairment.

These same investigators published a similar meta-analysis in 2008, looking at 12 studies.  Over the ensuing three years (as of June, 2010), seven new prospective cohort studies looked at the health benefits of the Mediterranean diet.  The report at hand is a combination of all 19 studies, covering over 2,000,000 participants followed for four to 20 years.  Nine of the 19 Mediterranean diet studies were done in Europe.

The newer studies, in particular, firmed up the diet’s protective effect against stroke, and added protection against mild cognitive impairment.

So What?

The Mediterranean diet: No other way of eating has so much scientific evidence that it’s healthy and worthy of adoption by the general population.  Not the DASH diet, not the “prudent diet,” not the American Heart Association diet, not vegetarian diets, not vegan diets, not raw-food diets, not Esselstyne’s diet, not Ornish’s diet, not Atkins diet, not Oprah’s latest diet, not the Standard American Diet, not the  . . . you name it. 

Not even the Low-Carb Mediterranean Diet.

Just as important, the research shows you don’t have to go full-bore Mediterranean to gain a health and longevity benefit.  Adopting  just a couple Mediterranean diet features yeilds a modest but sigificant gain.  For a list of Mediterranean diet components, visit Oldways or the Advanced Mediterranean Diet website. 

Steve Parker, M.D.

Reference:  Sofi, Francesco, et al.  Accruing evidence about benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis.  American Journal of Clinical Nutrition, ePub ahead of print, September 1, 2010.  doi: 10.3945/ajcn.2010.29673

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Filed under coronary heart disease, Health Benefits, Mediterranean Diet

Myth Busted: Alzheimer Dementia NOT Caused By Diabetes

Contrary to popular belief among the experts, type 2 diabetes is not one of the causes of Alzeimer dementia.  They may indeed be associated with each other, but that’s not causation. 

Brain CT scan

An oft-repeated theory from Gary Taubes 2007 masterpiece, Good Calories, Bad Calories, is that many of the chronic diseases of modern civilization, including Alzheimer disease, are caused by abnormal blood sugar and insulin metabolism.  Especially high insulin levels induced by a diet rich in refined carbohydrates.  If that’s the case, you’d expect to see a high prevalence of Alzheimer disease in older type 2 diabetics. 

Dr. Emily Deans (psychiatrist) has been considering this issue recently at her Evolutionary Psychiatry blog.

The brains of Alzheimer patients, under a microscope, are characterized by many senile plaques (aka neuritic plaques) and neurofibrillary tangles.  That’s the gold standard for diagnosis.  Nevertheless, brain biopsies are rarely done to diagnose Alzheimer disease in living patients, and even autopsies after death are rare.  The diagnosis usually is clinical, based on ruling out other illnesses, etc.

Nearly all the studies associating diabetes with Alzheimers disease (and other dementias) are observational or epidimiologic. [The exception is the Honolulu-Asia Aging Study.]  Establishing an association is helpful in generating theories, but establishing causation is the goal.  At least five studies confirm an association.

Neurology this year reported findings of Japanese researchers who examined the brains of 135 people who died between 1998 and 2003.  They lived in Hisayama, a town with an incredibly high autopsy rate of 74%.  These people before death had undergone an oral glucose tolerance test.  Their insulin resistance was calculated on the basis of fasting glucose and fasting insulin (HOMA-IR).  None of them showed signs of dementia at the time of study enrollment in 1988.

What Did They Find?

Twenty-one of the 135 subjects developed Alzheimer-type dementia.  The investigators don’t say if the diagnosis was based on the brain examination, or just a clinical diagnosis without a brain biopsy.  How this got beyond the article reviewers is beyond me.  [If I’m missing something, let me know in the comments section below.]  It must be a clinical diagnosis because if you don’t act demented, it doesn’t matter how many senile plaques and neurofibrillary tangles you have in your brain. 

ResearchBlogging.orgSenile plaques, but not neurofibrillary tangles, were more common  in those with higher levels of blood sugar (as measured two hours after the 75 g oral glucose dose), higher fasting insulin, and higher insulin resistance.  People with the APOE epsilon-4 gene were at even higher risk for developing senile plaques.

The researchers did not report whether the subjects in this study had been previously during life with diabetes or not.  One can only hope those data will be published in another paper.  Why make us wait? 

Average fasting glucose of all subjects was 106 mg/dl (5.9 mmol/l); average two-hour glucose after the oral glucose load was 149 mg/dl (8.3 mmol/l).  By American Association of Clinical Endocrinologists criteria, these are prediabetic levels.  Mysteriously, the authors fail to mention or discuss this.  [I don’t know if AACE criteria apply to Japanese.]  Some of these Japanese subjects probably had diabetes, some had prediabetes, others had normal glucose and insulin metabolism.

As with all good research papers, the authors compare their findings with similar published studies.  They found one autopsy study that tended to agree with their findings (Honolulu) and three others that don’t (see references below).  In fact, one of the three indicated that diabetes seems to protect against the abnormal brain tissue characteristic of Alzheimer disease.

Botton Line

Type 2 diabetes doesn’t seem to be a cause of Alzheimer disease, if autopsy findings and clinical features are the diagnostic criteria for the disease. 

If we assume that type 2 diabetics have higher than normal blood sugar levels and higher insulin levels for several years, then hyperglycemia and hyperinsulinemia don’t cause or contribute to Alzheimer dementia.  Myth busted.  [I hope that’s not copyrighted by the “Myth Busters” TV show.]

Type 2 diabetes is, however, linked with impaired cognitive performance, at least according to many of the scientific articles I read in preparation for this post.  So type 2 diabetics aren’t in the clear yet.  It’s entirely possible that high blood sugar and /or insulin levels cause or contribute to that.  [Any volunteers to do the literature review?  Best search term may be “mild cognitive impairment.”]

Type 2 diabetes is associated with Alzheimer disease, but we have no proof that diabetes is a cause of Alzheimers.  Nor do we have evidence that high blood sugar and insulin levels cause Alzheimer disease. 

Alzheimer disease is a major scourge on our society.  I’d love to think that carbohydrate-restricted eating would help keep blood sugar and insulin levels lower and thereby lessen the devastation of the disease.  Maybe it does, but I’d like to see more convincing evidence.  It’ll be years before we have a definitive answer. 

Steve Parker, M.D.

References:
Matsuzaki T, Sasaki K, Tanizaki Y, Hata J, Fujimi K, Matsui Y, Sekita A, Suzuki SO, Kanba S, Kiyohara Y, & Iwaki T (2010). Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. Neurology, 75 (9), 764-70 PMID: 20739649

Heitner, J.,  et al. “Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects: a retrospective postmortem immunocytochemical and histofluorescent study.” Neurology, 49 (1997): 1306-1311.  Autopsy study, No. of subjects not in abstract. They looked for senile plaques and neurofibrillary tangles, etc. The title says it all.

Beeri,  M.S., et al. “Type 2 diabetes is NEGATIVELY [emphasis added] associated with Alzheimer’s disease neuropathology.” J. Gerontol A. Biol Sci. Med. Sci. 60 (2005): 471-475.  385 autopsies. The title again says it all.

Arvanitakis, Z., et al. “Diabetes is related to cerebral infarction but NOT [emphasis added] to Alzheimers disease pathology in older persons.”  Neurology, 67 (2006): 1960-1965. Autopsy study of 233 Catholic clergy, about 50:50 women:men.

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Filed under Carbohydrate, Diabetes Complications

Maybe Diet Prevents Alzheimer Dementia After All

I blogged about a study by Gu et al on April 30, 2010, that found significantly lower incidence of Alzheimer dementia in people in Manhattan who followed this dietary pattern:

  • relatively high consumption of salad dressing, nuts, fish, tomatoes, fruits, dark green leafy vegetables, and cruciferous  vegetables
  • relatively low consumption of poultry, red meat, butter, and high-fat dairy

About the same time, a National Institutes of Health expert panel pooh-poohed the possibility that diet had any effect one way or the other on Alzheimer’s

Why does this matter?  Five million U.S. adults have Alzheimer dementia already, and it’s going to get much worse over the coming decades.

A June, 2010, issue of Journal of the American Medical Association has a commentary by two doctors (Martha Morris, Sc.D., and Christine Tangney, Ph.D.), experts in the field of nutrition.  Here’s their explanation of the NIH panel’s negative findings:

Many of the inconsistencies among studies of dietary factors can be attributed to the complexity of nutrition science and the omission of nutrition expertise in the design and analysis of both epidemiological and randomized controlled trials.

Morris and Tangney think the findings of Gu et al are valid, confirming prior studies showing benefit to diets high in vitamin E (from food) and low in saturated fat from animals.  They point out that the animal foods may simply be displacing beneficial nutrients in other foods, rather than directly causing harm.

Until we have further data, anyone at risk for Alzhiemer’s may be better off following the dietary pattern above, or the Mediterranean diet.  The two are similar.

Steve Parker, M.D.

Disclaimer:  All matters regarding your health require supervision by a personal physician or other appropriate health professional familiar with your current health status.  Always consult your personal physican before making any dietary or exercise changes. 

Reference: Morris, M., & Tangney, C.  Diet and Prevention of Alzheimer Disease.  The Journal of the American Medical Association, 303 (2010): 2,519-2,520.    doi: 10.1001/jama.2010.844

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Documented Health Benefits of the Mediterranean Diet

The enduring popularity of the Mediterranean diet is attributable to three things:

  1. Taste
  2. Variety
  3. Health benefits

 For our purposes today, I use “diet” to refer to the usual food and drink of a person, not a weight-loss program.

The scientist most responsible for the popularity of the diet, Ancel Keys, thought the heart-healthy aspects of the diet related to low saturated fat consumption.  He also thought the lower blood cholesterol levels in Mediterranean populations (at least Italy and Greece) had something to do with it, too.  Dietary saturated fat does tend to raise cholesterol levels, both LDL and HDL.

Even if Keys was wrong about saturated fat and cholesterol levels being positively associated with heart disease, numerous studies (involving eight countries on three continents) strongly suggest that the Mediterranean diet is one of the healthiest around.  See References below for the most recent studies.

Relatively strong evidence supports the Mediterranean diet’s association with:

■ increased lifespan

■ lower rates of cardiovascular disease such as heart attacks and strokes

■ lower rates of cancer (prostate, breast, uterus, colon)

■ lower rates of dementia

■ lower incidence of type 2 diabetes

 

Weaker supporting evidence links the Mediterranean diet with:

■ slowed progression of dementia

■ prevention of cutaneous melanoma

■ lower severity of type 2 diabetes, as judged by diabetic drug usage and fasting blood sugars

■ less risk of developing obesity

■ better blood pressure control in the elderly

■ improved weight loss and weight control in type 2 diabetics

■ improved control of asthma

■  reduced risk of developing diabetes after a heart attack

■ reduced risk of mild cognitive impairment

■  prolonged life of Alzheimer disease patients

■ lower rates and severity of chronic obstructive pulmonary disease

■ lower risk of gastric (stomach) cancer

■ less risk of macular degeneration

■ less Parkinsons disease

■ increased chance of pregnancy in women undergoing fertility treatment

■  reduced prevalence of metabolic syndrome (when supplemented with nuts)

■ lower incidence of asthma and allergy-like symptoms in children of women who followed the Mediterranean diet while pregnant

Did you notice that I used the word “association” in relating the Mediterranean diet to health outcomes?  Association, of course, is not causation. 

The way to prove that a particular diet is healthier is to take 20,000 similar young adults, randomize the individuals  in an interventional study to eat one of two test diets for the next 60 years, monitoring them for the development of various diseases and death.  Make sure they stay on the assigned test diet.  Then you’d have an answer for that population and those two diets.  Then you have to compare the winning diet to yet other diets.  And a study done in Caucasians would not necessarily apply to Asians, Native Americans, Blacks, or Hispanics.

Now you begin to see why scientists tend to rely on observational  rather than interventional diet studies.

I became quite interested in nutrition around the turn of the century as my patients asked me for dietary advice to help them lose weight and control or prevent various diseases.  At that time, the Atkins diet, Mediterranean diet, and Dr. Dean Ornish’s vegetarian program for heart patients were all prevalent.  And you couldn’t pick three programs with more differences!  So I had my work cut out for me. 

After much scientific literature review, I find the Mediterranean diet to be the healthiest for the general population.  People with particular medical problems or ethnicities may do better on another diet.  A low-carb Mediterranean diet should be healthier for type 2 diabetics.  Dan Buettner makes a good argument for plant-based diets in his longevity book, The Blue Zones.  The traditional Mediterranean diet qualifies as plant-based.

What do you consider the overall healthiest diet, and why?

Steve Parker, M.D.

References:

Buckland, Genevieve, et al.  Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort studyAmerican Journal of Clinical Nutrition, December 9, 2009, epub ahead of print.  doi: 10.3945/ajcn.2009.28209

Fortes, C., et al.  A protective effect of the Mediterraenan diet for cutaneous melanoma.  International Journal of Epidmiology, 37 (2008): 1,018-1,029.

Sofi, Francesco, et al.  Adherence to Mediterranean diet and health status: Meta-analysis.  British Medical Journal, 337; a1344.  Published online September 11, 2008.  doi:10.1136/bmj.a1344

Benetou, V., et al.  Conformity to traditional Mediterranean diet and cancer incidence: the Greek EPIC cohort.  British Journal of Cancer, 99 (2008): 191-195.

Mitrou, Panagiota N., et al.  Mediterranean Dietary Pattern and Prediction of All-Cause Mortality in a US Population,  Archives of Internal Medicine, 167 (2007): 2461-2468.

Feart, Catherine, et al.  Adherence to a Mediterranean diet, cognitive decline, and risk of dementia.  Journal of the American Medical Association, 302 (2009): 638-648.

Scarmeas, Nikolaos, et al.  Physical activity, diet, and risk of Alzheimer Disease.  Journal of the American Medical Association, 302 (2009): 627-637.

Scarmeas, Nikolaos, et al.  Mediterranean Diet and Mild Cognitive Impairment.  Archives of Neurology, 66 (2009): 216-225.

Scarmeas, N., et al.  Mediterranean diet and Alzheimer disease mortality.  Neurology, 69 (2007):1,084-1,093.

Fung, Teresa, et al.  Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women.  Circulation, 119 (2009): 1,093-1,100.

Mente, Andrew, et al.  A Systematic Review of the Evidence Supporting a Causal Link Between Dietary Factors and Coronary Heart DiseaseArchives of Internal Medicine, 169 (2009): 659-669.

Salas-Salvado, Jordi, et al.  Effect of a Mediterranean Diet Supplemented With Nuts on Metabolic Syndrome Status: One-Year Results of the PREDIMED Randomized Trial.  Archives of Internal Medicine, 168 (2008): 2,449-2,458.

Mozaffarian, Dariush, et al.  Incidence of new-onset diabetes and impaired fasting glucose in patients with recent myocardial infarction and the effect of clinical and lifestyle risk factors.  Lancet, 370 (2007) 667-675.

Esposito, Katherine, et al.  Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetesAnnals of Internal Medicine, 151 (2009): 306-314.

Shai, Iris, et al.  Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet.  New England Journal of Medicine, 359 (2008): 229-241.

Martinez-Gonzalez, M.A., et al.  Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study.  British Medical Journal, BMJ,doi:10.1136/bmj.39561.501007.BE (published online May 29, 2008).

Trichopoulou, Antonia, et al.  Anatomy of health effects of the Mediterranean diet: Greek EPIC prospective cohort studyBritish Medical Journal, 338 (2009): b2337.  DOI: 10.1136/bmj.b2337.

Barros, R., et al.  Adherence to the Mediterranean diet and fresh fruit intake are associated with improved asthma control.  Allergy, vol. 63 (2008): 917-923.

Varraso, Raphaelle, et al.  Prospective study of dietary patterns and chronic obstructive pulmonary disease among US men.  Thorax, vol. 62, (2007): 786-791

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“Dementia Runs In My Family. Does Food Affect MY Risk?”

New York researchers reported in Archives of Neurology this month that a particular eating pattern does seem to lower the risk of Alzheimers Disease, the most common type of dementia.  Manhattanites were significantly less likely to develop dementia if they had . . .

Higher consumption of:

  • salad dressing
  • nuts
  • tomatoes
  • fish
  • poultry
  • cruciferous vegetables (e.g., cabbage, radish, broccoli, kale, collard greens, cauliflower, turnips, brussels sprouts)
  • fruits
  • dark and green leafy vegetables

Lower consumption of:

  • high-fat dairy products
  • red meat
  • organ meats
  • butter

The study involved over 2000 people over age 65 who were followed for the onset of dementia over four years.  The researchers used a sophisticated analytic technique called “reduced rank regression.”  See the original article for details.

The study authors note similarities of this dietary pattern to the Mediterranean diet, long associated with lower risk of dementia.  They also document (again) the strong association of moderate alcohol consumption with lower dementia risk, although it was not part of their predetermined anaylytic technique.

Alzheimers Dementia has a strong tendency to run in some families.  As lifespans increase, we’re going to be seeing lots more of it.  If you make it to age 85, your odds of having dementia are 50:50.

If you worry about developing Alzheimers, perhaps because of family history, you may be doing yourself and others a favor by adopting either the dietary pattern above or the Mediterranean diet.

On the other hand . . .

MedPageToday on April 28, 2010, reported the conclusions of a panel convened by the (U.S.) National Institutes of Health:

The independent panel . . . determined that the causes of Alzheimers disease are still unknown and that no reliable evidence has shown that anything can prevent the disease or stop it from progressing.

Steve Parker, M.D.

Disclaimer:  All matters regarding your health require supervision by a personal physician or other appropriate health professional familiar with your current health status.  Always consult your personal physician before making any dietary or exercise changes.

References: 

Gu, Yian, et al.  Food combination and Alzheimer Disease riskArchives of Neurology, 67 (2010).  Epub ahead of print.  doi: 10.1001/archneurol.2010.84

Walker, Emily P.  NIH panel provides no help in unraveling Alzheimers diseaseMedPageToday, April 28, 2010.  Accessed online April 28, 2010.

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