Tag Archives: Stroke

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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Filed under Diabetes Complications

Exercise, Part 1: Exercise Postpones Death

Earlier this month, many folks made New Years’ resolutions to start exercising in conjunction with their other resolution to lose excess weight. I’ve got bad news for them.

Exercise is overrated as a pathway to major weight loss.

Sure, a physically inactive young man with only five or 10 pounds (2 to 4 kg) to lose might be able to do it simply by starting an exercise program. That doesn’t work nearly as well for women. The problem is that exercise stimulates appetite, so any calories burned by exercise tend to be counteracted by increased food consumption.

"Should I go with aerobic or strength training....?"

On the other hand, exercise is particularly important for diabetics and prediabetics in two respects: 1) it helps in avoidance of overweight, especially after weight loss, and 2) it helps control blood sugar levels by improving insulin resistance, perhaps even bypassing it.

Even if it doesn’t help much with weight loss, regular physical activity has myriad general health benefits. First, let’s look at its effect on death rates.   

EXERCISE PREVENTS DEATH

As many as 250,000 deaths per year in the United States (approximately 12% of the total) are attributable to a lack of regular physical activity. We know now that regular physical activity can prevent a significant number of these deaths.

Exercise induces metabolic changes that lessen the impact of, or prevent altogether, several major illnesses, such as high blood pressure, coronary artery disease, diabetes, and obesity. There are also psychological benefits. Even if you’re just interested in looking better, awareness of exercise’s other advantages can be motivational.

Exercise is defined as planned, structured, and repetitive bodily movement done to improve or maintain physical fitness.

Physical fitness is a set of attributes that relate to your ability to perform physical activity. These attributes include resting heart rate, blood pressure at rest and during exercise, lung capacity, body composition (weight in relation to height, percentage of body fat and muscle, bone structure), and aerobic power.

Aerobic power takes some explanation. Muscles perform their work by contracting, which shortens the muscles, pulling on attached tendons or bones. The resultant movement is physical activity. Muscle contraction requires energy, which is obtained from chemical reactions that use oxygen. Oxygen from the air we breathe is delivered to muscle tissue by the lungs, heart, and blood vessels. The ability of the cardiopulmonary system to transport oxygen from the atmosphere to the working muscles is called maximal oxygen uptake, or aerobic power. It’s the primary factor limiting performance of muscular activity.

Aerobic power is commonly measured by having a person perform progressively more difficult exercise on a treadmill or bicycle to the point of exhaustion. The treadmill test starts at a walking pace and gets faster and steeper every few minutes. The longer the subject can last on the treadmill, the greater his aerobic power. A large aerobic power is one of the most reliable indicators of good physical fitness. It’s cultivated through consistent, repetitive physical activity.

Physical Fitness Effect on Death Rates

Regular physical activity postpones death.

Higher levels of physical fitness are linked to lower rates of death primarily from cancer and cardiovascular disease (e.g., heart attacks and stroke). What’s more, moving from a lower to a higher level of fitness also prolongs life, even for people over 60.

Part 2 of this series will cover all the other health benefits of exercise. Part 3 will outline specific exercise recommendations, such as the type and duration of activity.

Steve Parker, M.D.

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Asian Strokes Are Not Same as Western

The higher the consumption of saturated fat, the lower the risk of death from stroke, according to Japanese researchers in a recent American Journal of Clinical Nutrition

Most physicians in the West would have predicted the opposite: saturated fats increase your risk of stroke.  Western physicians tend to think most strokes and heart attacks are caused by the same process, atherosclerosis, and would be aggravated by saturated fat consumption.  We’re learning that ain’t necessarily so.

Most strokes in the Western world are thought to be linked to atherosclerosis (hardening of the arteries) of relatively large arteries. In Japan, most strokes not caused by bleeding in the head are actually lacunar infarctions involving small arteries in the brain, not necessarily involving atherosclerosis

Another major difference between East and West is that saturated fat consumption in Japan is far lower than in the West.

Are you confused yet?

It seems to me that comparing strokes in Japan versus the West is comparing apples to oranges.  The take-away point to me is that we have to be quite wary of generalizing the research results applicable to one culture or ethnic group, to others.

By the way, stroke had been the third leading cause of death in the U.S. for the last 50 years.  It was recently demoted to fourth place by chronic lower respiratory disease.  The traditional Mediterranean diet is one way to reduce your risk of stroke, and the DASH diet works for women.  Keeping your blood pressure under 140/90 is another.  And don’t smoke.

Steve Parker, M.D.

Reference:  Yamagishi, Kazumasa, et al.  Dietary intake of saturated fatty acids and mortality from cardiovascular disease in Japanese: the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Study.  American Journal of Clinical Nutrition, August 4, 2010.  doi: 10.3945/ajcn.2009.29146

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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

Heart and Stroke Patients: Avoid Weight-Loss Drug Sibutramine (Meridia)

The weight-loss drug sibutramine (Meridia) should be withdrawn from the U.S. market, suggests an editorialist in the September 2, 2010, New England Journal of Medicine.  Based on a clinical study in the same issue, it’s more accurate to conclude that sibutramine shouldn’t be prescribed for people who aren’t supposed to be taking it in the first place.

Sibutramine is sold in the U.S. as Meridia and has been available since 1997.  Judging from the patients I run across, it’s not a very popular drug.  Why not?  It’s expensive and most people don’t lose much weight.

The recent multi-continent SCOUT trial enrolled 9,800 male and female study subjects at least 55 years old (average age 63) who had either:

  1. 1) History of cardiovascular disease (here defined as coronary artery disease, stroke, or peripheral artery disease)
  2. 2) Type 2 diabetes plus one or more of the following: high blood pressure, adverse cholesterol levels, current smoking, or diabetic kidney disease.
  3. Or both of the above (which ended up being 60% of the study population)`.

Here’s a problem from the get-go (“git-go” if you’re from southern U.S.).  For years, Meridia’s manufacturer and the U.S. Food and Drug Administration have told doctors they shouldn’t use the drug in patients with history of cardiovascular disease.  It’s not the scary “black box warning,” but it’s clearly in the package insert of full prescribing information.

Half the subjects were randomized to sibutramine 10 mg/day and the other half to placebo.  All were instructed in diet and exercise aiming for a 600 calorie per day energy deficit.  They should lose about a pound a week if they followed the program.  Average follow-up was 3.4 years.

What Did the Researchers Find?

Forty percent of both drug and placebo users dropped out of the study, a very high rate.

As measured at one year, the sibutramine-users averaged a weight loss of 9.5 pounds (4.3 kg), the majority of which was in the first 6 weeks.  After the first year, they tended to regain a little weight, but kept most of it off.

Death rates were the same for sibutramine and placebo.

Sibutramine users with a history of cardiovascular disease had a 16% increase in non-fatal heart attack and stroke compared to placebo.  To “cause” one heart attack or stroke in a person with known cardiovascular disease, you would have to treat 52 such patients.

Folks in the “diabetes plus risk factor(s)” group who took sibutramine had no increased risk of heart attack or stroke.

So What?

Average weight loss with sibutramine isn’t much.  Nothing new there.  [Your mileage may vary.]

People with cardiovascular disease shouldn’t take sibutramine.  Nothing new there either.

Steve Parker, M.D.

Reference:  James, W. Philip, et al.  Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.  New England Journal of Medicine, 363 (2010): 905-917.

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Filed under coronary heart disease, Drugs for Diabetes, Overweight and Obesity, Stroke, Weight Loss

Diabetes and Shortened Lifespan: “How Bad Is It, Doc?”

Diabetes mellitus for years has been linked with cardiovascular disease such as heart failure and coronary heart disease (blocked arteries in the heart, and the leading cause of death in the Western world).  How scared should diabetics be?

An article  in the Archives of Internal Medicine gives us one answer.

Researchers from the Netherlands and Harvard examined medical records of 5,209 people (mostly white, 64% men) enrolled in the Framingham (Massachusetts, USA) Heart Study.  This cohort has been examined every other year for more than 46 years. 

Study subjects who had diabetes at age 50 were identified; health outcomes going forward were then analyzed, with particular attention to lifespan and cardiovascular disease.  “Cardiovascular disease” in this context means coronary heart disease, stroke, congestive heart failure, intermittent claudication (leg pain during exertion caused by blocked arteries), and transient ischemic attack (stroke-like symptoms that resolve within 24 hours).

Results

Compared to those in the cohort free of diabetes, having diabetes at age 50 more than doubled the risk of developing cardiovascular disease for both women and men. 

Compared to those without diabetes, having both cardiovascular disease and diabetes approximately doubled the risk of dying, regardless of sex.

Compared to those without diabetes, women and men with diabetes at age 50 died 7 or 8 years earlier, on average.

[Specific causes of death were not reported.]

Take-Home Points

We’d likely see longer lifespans and less cardiovascular disease if we could prevent diabetes in the first place.  How do we do that?  Strategies include regular physical activity, avoidance or reversal of overweight and obesity, and low-glycemic-index diets.

The Mediterranean diet it linked to reduced heart attacks and strokes, and longer lifespan.  That’s why I’ve been working for the last year and a half to adapt it for diabetics.

ResearchBlogging.orgWe have better treatments for cardiovascular disease and diabetes and these days, so the death rates and illness numbers shouldn’t  be quite so alarming.  Up-to-date management of diabetes and cardiovascular disease will prevent some acute disease events—such as heart attacks and strokes—and prolong life.   

Steve Parker, M.D.

References: 

Franco, O., Steyerberg, E., Hu, F., Mackenbach, J., & Nusselder, W. (2007). Associations of Diabetes Mellitus With Total Life Expectancy and Life Expectancy With and Without Cardiovascular Disease Archives of Internal Medicine, 167 (11), 1145-1151 DOI: 10.1001/archinte.167.11.1145

Knowler, W.C., et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.  New England Journal of Medicine, 346 (2002): 393-403.

Tuomilehto, J., et al.  Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.  New England Journal of Medicine, 344 (2001): 1,343-1,350.

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Filed under coronary heart disease, Diabetes Complications, Stroke

Rosiglitazone On the Ropes

A week ago, MedPageToday reported that a British advisory commission recommended the diabetes drug rosiglitazone (Avandia) be withdrawn from the market.

On July 6, I wrote about evidence that rosiglitazone users seem to incur a higher risk of stroke, heart failure, and death.

If I were taking Avandia, I’d be asking my doctor about alternatives. 

Steve Parker, M.D.

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