Category Archives: Dementia

Do Fruits and Vegetables Prevent Disease? Which Ones?

Posted on January 31, 2013 | Comments Off on Do Fruits and Vegetables Prevent Disease? Which Ones?

Potential answers are in the American Journal of Clinical Nutrition (2012).  I quote:

For hypertension, coronary heart disease, and stroke, there is convincing evidence that increasing the consumption of vegetables and fruit reduces the risk of disease. There is probable evidence that the risk of cancer in general is inversely associated with the consumption of vegetables and fruit. In addition, there is possible evidence that an increased consumption of vegetables and fruit may prevent body weight gain. As overweight is the most important risk factor for type 2 diabetes mellitus, an increased consumption of vegetables and fruit therefore might indirectly reduces the incidence of type 2 diabetes mellitus. Independent of overweight, there is probable evidence that there is no influence of increased consumption on the risk of type 2 diabetes mellitus. There is possible evidence that increasing the consumption of vegetables and fruit lowers the risk of certain eye diseases, dementia and the risk of osteoporosis. Likewise, current data on asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis indicate that an increase in vegetable and fruit consumption may contribute to the prevention of these diseases. For inflammatory bowel disease, glaucoma, and diabetic retinopathy, there was insufficient evidence regarding an association with the consumption of vegetables and fruit.

It bothers me that vegetables and fruits are lumped together: they’re not the same.

All of my diets—Advanced Mediterranean, Low-Carb Mediterranean, and Ketogenic Mediterranean—provide plenty of fruits and vegetables.

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Posted in Coronary Heart Disease, Dementia, Diabetes, Heart Disease, Low-Carb Mediterranean Diet, Lungs, Osteoporosis, Stroke

Carbohydrates and Sugar Raise Risk of Elderly Cognitive Impairment

Posted on October 17, 2012 | Comments Off on Carbohydrates and Sugar Raise Risk of Elderly Cognitive Impairment

The Mayo Clinic recently reported that diets high in carbohydrates and sugar increase the odds of developing cognitive impairment in the elderly years.

Mild cognitive impairment is often a precursor to incurable dementia.  Many authorities think dementia develops more often in people with diabetes, although some studies refute the linkage.

Researchers followed 940 patients with normal baseline cognitive functioning over the course of four years. Diet was assessed via questionnaire. Study participants were ages 70 to 89. As the years passed, 200 of them developed mild cognitive impairment.

Compared with those eating at the lowest level of carbohydrate consumption, those eating at the highest levels were almost twice as likely to go to develop mild cognitive impairment.

The scientists note that those eating lower on the carbohydrate continuum were eating more fats and proteins.

Steve Parker, M.D.

 

 

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Huge Study Confirms Health and Longevity Benefits of Mediterranean Diet

Posted on June 27, 2012 | Comments Off on Huge Study Confirms Health and Longevity Benefits of Mediterranean Diet

Italian researchers reported in the September 11, 2008, online issue of the British Medical Journal what is already known:

“Greater adherence to a Mediterranean diet is associated with a significant improvement in health status, as seen by a significant reduction in overall mortality (9%), mortality from cardiovascular diseases (9%), incidence of or mortality from cancer (6%), and incidence of Parkinsons’s disease and Alzheimer’s disease (13%).  These results seem to be clinically relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of major chronic diseases.”

Methodology

Researchers, mostly at the University of Florence, performed a meta-analysis of 12 other published studies that looked at the effects of a Mediterranean-style eating pattern on health and longevity.  [Meta-analyses are popular, in part, because they are cheap.  This study required no specific funding.]

Most, if not all, of these 12 studies were observational, and involved 1,574,299 participants.  Six of the 12 studies were in Mediterranean countries, the others were in the U.S., northern Europe, and Australia.  Study participants were followed between 3.7 and 18 years.

The researchers devised their very own Mediterranean diet scale based on study participants’ intake of various foods.  Participants were given a point if they had higher than average intake of vegetables, fruits, legumes, cereals, fish, and red wine during meals.  They were given a point if they had lower than average intake of red meat, processed meats, and dairy products.  Due to differences among the 12 studies, “the total adherence scores…varied from a minimum of 0 points indicating low adherence to a maximum of 7-9 points reflecting high adherence to a Mediterranean diet.”

(This version of a Mediterranean diet score is problematic.  Curiously, olive oil – the predominant source of fat in the traditional Mediterranean – is not in the score.  Olive oil is a key characteristic of the Mediterranean diet.  Furthermore, the study authors also state that dairy products are “presumed not to form part of a Mediterranean diet.”  Most experts would argue that cheese and yogurt are a significant part of the Mediterranean diet, if only in low amounts.  I also doubt that participants in the 12 original studies  were surveyed whether they drank red wine – as contrasted with white – and whether it was with meals or not.  I admit I did not read each of the 12 component studies.  The underlying cause of this idiosyncratic definition of the Mediterranean diet is that the 12 original studies themselves used different definitions of the Mediterranean diet.  The meta-analysts had to pigeonhole the data.  There are a handful of respected Mediterranean diet scores in existence, but the authors of this study couldn’t apply them across the board due to database inconsistency or inadequacy.)

Results

“The cumulative analysis of 12 cohort studies shows that a two point increase [emphasis added] in the score for adherence to a Mediterranean diet determines a 9% reduction, in overall mortality, a 9% reduction in mortality from cardiovascular diseases, a 6% reduction in incidence of or mortality from neoplasm [cancer], and 13% reduction in incidence of Parkinson’s disease and Alzheimer’s disease.”

The only one of the 12 original studies focused on Alzheimer’s disease, and it showed a 17% reduction in participants with high adherence to the Mediterranean diet.  The two studies that focused on Parkinson’s disease revealed a 7% reduction in men, and 15% reduction in women.  These reduced incidence figures, again, apply to a two-point increase in Mediterranean diet adherence score.

Discussion

The authors indicate that their report is the first ever meta-analysis of the data associating the Mediterranean diet with reduced mortality and chronic disease in the general population.  Congratulations, guys!

The authors’ idiosyncratic Mediterranean diet score is unusual and won’t be widely adopted.  However, the 12 studies comprising the meta-analysis did have reasonable Mediterranean diet characteristics.

Combining Alzheimer’s data with Parkinson’s data doesn’t make sense to me, nor did the authors try to explain it.   You could lump them into the category of “neurodegenerative diseases,” but they aren’t the only ones by any means.  The single Alzheimer’s study, by the way, was quite small compared to the two Parkinson’s studies.

Nearly all the popular media stories reported the findings as I did in my first paragraph above, which may be  misleading.  The specific improvements in mortality and various disease rates is per two-point increase in Mediterranean diet score.  For example, consider the 9% reduction in overall mortality.  If a population increased its Mediterranean score by four points, would overall mortality be reduced by 18%?  I’ve read this study four times and cannot answer my own question.  But I suspect that the answer is “yes.”  So the news here may better than it seems at first blush.

In other words: If a population’s score goes from 5 to 7, the death rate is reduced by 9%.  If that same population then moved its score from 7 to 9, would mortality improve another 9%?  I think so, but this study as written does not make it clear.

I’m starting to see why the popular media simplified the study findings.  The reporting on this study is amazingly uniform.  They must have all gotten the same news release.

Of course, “populations” don’t die or get cancer, heart attacks, strokes, Alzheimer’s, or Parkinson’s disease.  Individuals do that.  If I as an individual had a low Mediterranean diet score, I’d try to improve my score by at least two points.  A good place to start would be a review of the Mediterranean diet.

Steve Parker, M.D.

Reference:  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

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Posted in Alzheimer Disease, Cancer, Coronary Heart Disease, Dementia, Heart Disease, Longevity

Omega-3 Fatty Acid Supplements Fail to Stall Age-Related Brain Decline

Posted on June 13, 2012 | Comments Off on Omega-3 Fatty Acid Supplements Fail to Stall Age-Related Brain Decline

I like fish, but cold whole dead fish leave me cold

Supplementation with omega-3 fatty acids does not help prevent age-related cognitive decline or dementia, according to an article at MedPage Today.

The respected Cochrane organization did a meta-analysis of three pertinent studies done in several countries (Holland, UK, and ?).

The investigators leave open the possibility that longer-term studies—over three years—may show some benefit.

I leave you with a quote from the MedPage Today article:

And while cognitive benefits were not demonstrated in this review, Sydenham and colleagues emphasized that consumption of two servings of fish each week, with one being an oily fish such as salmon or sardines, is widely recommended for overall health benefits.

Steve Parker, M.D.

Reference:
Sydenham E, et al “Omega 3 fatty acid for the prevention of cognitive decline and dementia” Cochrane Database of Systematic Reviews 2012; DOI: 10.1002/14651858.CD005379.pub3.

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Mediterranean Diet Reduces Risk of Mild Cognitive Impairment

Posted on June 1, 2012 | 1 comment

Mild Cognitive Impairment (MCI) is considered a precursor to dementia, although it does not always lead to dementia.

A study published in 2009 in the Archives of Neurology indicates that adherence to the Mediterranean diet reduces both the risk of developing MCI and the risk of MCI conversion to Alzheimer dementia.

Methodology

1,393 residents of a multi-ethnic community in New York were enrolled in the study. They were mentally normal at baseline and followed for an average of 4.5 years.

Another 482 residents were identified as having Mild Cognitive Impairment at baseline, and were followed an average of 4.3 years.

All participants were screened for cognitive impairments and surveyed to get an idea of usual food intake. Researchers used a 10-point scale to describe an individual participant’s adherence to the Mediterranean diet. The higher the score, the greater the participant’s adherence. Participants were then divided into thirds (tertiles) based on whether adherence was low, medium, or high. Average age of study subjects on entry was 77.

Results

275 of the 1,393 participants who were mentally normal at baseline developed Mild Cognitive Impairment over the 4.5 years of follow-up. Compared to those participants in the lowest third of Mediterranean diet adherence, those in the middle third had 17% less risk of developing MCI, and those in the highest third had 28% less risk.

Of 482 participants with Mild Cognitive Impairment at baseline, 106 later developed Alzheimer disease. Compared with participants in the lowest third of adherence, those in the middle third had 45% less risk of developing Alzheimer disease, and those in the highest third had 48% less risk.

Comments From the Study Authors

. . . potentially beneficial effects for mild cognitive impairment or mild cognitive impairment conversion to Alzheimer’s disease have been reported for alcohol, fish, polyunsaturated fatty acids (also for age-related cognitive decline) and lower levels of saturated fatty acids.

The Mediterranean diet tends to improve cholesterol levels, overall blood vessel function, reduce inflammation, and lower blood sugar levels, all of which could help preserve brain function.

My Comments

No surprise here.

The traditional Mediterranean diet has long been associated with lower risk of developing dementia, both Alzheimer and vascular dementia. Vascular dementia results from multiple strokes or poor blood flow to the brain. Since Mild Cognitive Impairment precedes Alzheimer dementia, it makes sense that the Mediterranean diet could help prevent both.

The lead author of the study at hand, Dr. Scarmeas, also reported in 2007 that the Mediterranean diet also prolongs life in established Alzheimer patients.

Steve Parker, M.D.

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

Additional Resource: Oldways’ Mediterranean diet information

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Mediterranean Diet Failed to Prevent Mental Decline in Women With Vascular Disease

Posted on May 30, 2012 | Comments Off on Mediterranean Diet Failed to Prevent Mental Decline in Women With Vascular Disease

Unfortunately, the Mediterranean diet failed to preserve cognitive function over the course of five years in the Women’s Antioxidant Cardiovascular Study (WACS).  The 2,500 women in the study, all over 65, at baseline had vascular disease or at least three risk factors for vascular disease.

Note that this research says nothing about prevention of age-related cognitive decline and Alzheimer dementia in women who don’t have baseline vascular disease.  The Mediterranean diet seems to help that population.

Steve Parker, M.D.

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Dental Problems and Chronic Systemic Disease: A Carbohydrate Connection?

Posted on May 21, 2012 | 1 comment

Dentists are considering a return to an old theory that dietary carbohydrates first cause dental diseases, then certain systemic chronic diseases, according to a review in the June 1, 2009, Journal of Dental Research.

We’ve known for years that some dental and systemic diseases are associated with each other, both for individuals and populations. For example, gingivitis and periodontal disease are associated with type 2 diabetes and coronary heart disease. The exact nature of that association is not clear. In the 1990s it seemed that infections – chlamydia, for example – might be the unifying link, but this has not been supported by subsequent research.

The article is written by Dr. Philippe P. Hujoel, who has been active in dental research for decades and is affiliated with the University of Washington (Seattle). He is no bomb-throwing, crazed, radical.

The “old theory” to which I referred is the Cleave-Yudkin idea from the 1960s and ’70s that excessive intake of fermentable carbohydrates, in the absence of good dental care, leads both to certain dental diseases – caries (cavities), periodontal disease, certain oral cancers, and leukoplakia – and to some common systemic chronic non-communicable diseases such as coronary heart disease, type 2 diabetes, some cancers, and dementia. In other words, dietary carbohydrates cause both dental and systemic diseases – not all cases of those diseases, of course, but some.

Dr. Hujoel does not define “fermentable” carbohydrates in the article. My American Heritage Dictionary defines fermentation as:

  1. the anaerobic conversion of sugar to carbon dioxide and alcohol by yeast
  2. any of a group of chemical reactions induced by living or nonliving ferments that split complex organic compunds into relatively simple substances

As reported in David Mendosa’s blog at MyDiabetesCentral.com, Dr. Hujoel said, “Non-fermentable carbohydrates are fibers.” Dr. Hujoel also shared some personal tidbits there.

In the context of excessive carbohydrate intake, the article frequently mentions sugar, refined carbs, and high-glycemic-index carbs. Dental effects of excessive carb intake can appear within weeks or months, whereas the sysemtic effects may take decades.

Hujoel compares and contrasts Ancel Keys’ Diet-Heart/Lipid Hypothesis with the Cleave-Yudkin Carbohydrate Theory. In Dr. Hujoel’s view, the latest research data favor the Carbohydrate Theory as an explanation of many cases of the aforementioned dental and systemic chronic diseases. If correct, the theory has important implications for prevention of dental and systemic diseases: namely, dietary carbohydrate restriction.

Adherents of the paleo diet and low-carb diets will love this article; it supports their choices.

I agree with Dr. Hujoel that we need a long-term prospective trial of serious low-carb eating versus the standard American high-carb diet. Take 20,000 people, randomize them to one of the two diets, follow their dental and systemic health over 15-30 years, then compare the two groups. Problem is, I’m not sure it can be done. It’s hard enough for most people to follow a low-carb diet for four months. And I’m asking for 30 years?!

Dr. Hujoel writes:

Possibly, when it comes to fermentable carbohydrates, teeth would then become to the medical and dental professionals what they have always been for paleoanthropologists: “extremely informative about age, sex, diet, health.”

Dr. Hujoel mentioned a review of six studies that showed a 30% reduction in gingivitis score by following a diet moderately reduced in carbs. He mentions the aphorism: “no carbohydrates, no caries.” Anyone prone to dental caries or ongoing periodontal disease should do further research to see if switching to low-carb eating might improve the situation.

Don’t be surprised if your dentist isn’t very familiar with the concept. Has he ever mentioned it to you?

Steve Parker, M.D.

Reference: Hujoel, P. Dietary carbohydrates and dental-systemic diseases. Journal of Dental Research, 88 (2009): 490-502.

Mendosa, David. Our dental alarm bell. MyDiabetesCentral.com, July 12, 2009.

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Documented Health Benefits of the Mediterranean Diet

Posted on May 5, 2012 | Comments Off on 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.

 

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 individualsin 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 observationalrather 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. People with diabetes or prediabetes are probably better off with a carbohydrate-restricted diet, such as the Low-Carb Mediterranean Diet.

 

Dan Buettner makes a good argument for plant-based diets in his longevity book, The Blue Zones.The Mediterranean diet qualifies as plant-based.

 

Steve Parker, M.D.

 

     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

     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 study. American 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 Disease. Archives 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 diabetes. Annals 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 study. British 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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Posted in Alzheimer Disease, Cancer, Coronary Heart Disease, Dementia, Diabetes, Heart Disease, High Blood Pressure, Longevity, Parkinson's Disease, Stroke

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Does Diabetes Cause Dementia?

Posted on May 2, 2012 | 1 comment

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.

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) looked at this issue last year at her great 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 epidemiologic. (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 in 2011 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 or autopsy. 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.

Senile 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 diagnosed 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.

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.

For now, we have evidence that the Mediterranean diet seems to 1) protect againstAlzheimers and other dementias, 2) prevent some cases of type 2 diabetes, and 3) reduce the need for diabetic medications in diabetics.

For more information on practical application of the Mediterranean diet, visit Oldways and the Advanced Mediterranean Diet website.

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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Vitamins Slow Rate of Brain Shrinkage in Elderly

Posted on April 25, 2012 | Comments Off on Vitamins Slow Rate of Brain Shrinkage in Elderly

A cocktail of three common B 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.

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 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 0.8 mg, B12 0.5 mg, and B6 20 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, A., Smith, S., de Jager, C., Whitbread, P., Johnston, C., Agacinski, G., Oulhaj, A., Bradley, K., Jacoby, R., & Refsum, H. (2010). Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial PLoS ONE, 5 (9) DOI: 10.1371/journal.pone.0012244

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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