Johns Hopkins Medicine
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CHOCOLATE "OFFENDERS" TEACH SCIENCE A SWEET LESSON
-- Study helps explain heart benefits from daily - but small - dose of chocolate

(Oral presentation #11865, Room S106b, Chicago Convention Center)

Some "chocoholics" who just couldn't give up their favorite treat to comply with a study to test blood stickiness have inadvertently done their fellow chocolate lovers - and science - a big favor.

Their "offense," say researchers at Johns Hopkins led to what is believed to be the first biochemical analysis to explain why just a few squares of chocolate a day can almost halve the risk of heart attack death in some men and women by decreasing the tendency of platelets to clot in narrow blood vessels.

"What these chocolate 'offenders' taught us is that the chemical in cocoa beans has a biochemical effect similar to aspirin in reducing platelet clumping, which can be fatal if a clot forms and blocks a blood vessel, causing a heart attack," says Diane Becker, M.P.H., Sc.D., a professor at the Johns Hopkins University's School of Medicine and Bloomberg School of Public Health.

Becker cautions that her work is not intended as a prescription to gobble up large amounts of chocolate candy, which often contains diet-busting amounts of sugar, butter and cream. But as little as 2 tablespoons a day of dark chocolate - the purest form of the candy, made from the dried extract of roasted cocoa beans - may be just what the doctor ordered.

Researchers have known for nearly two decades that dark chocolate, rich in chemicals called flavonoids, lowers blood pressure and has other beneficial effects on blood flow. The latest Johns Hopkins findings, to be presented Nov. 14 at the American Heart Association's annual Scientific Sessions in Chicago, identified the effect of normal, everyday doses of chocolate found in ordinary foods, unlike previous studies that found decreased platelet activity only at impractically high doses of flavonoids equivalent to eating several pounds of chocolate a day.

"Eating a little bit of chocolate or having a drink of hot cocoa as part of a regular diet is probably good for personal health, so long as people don't eat too much of it, and too much of the kind with lots of butter and sugar," says Becker.

In the study, 139 people Becker - whom Becker somewhat tongue in cheek calls "chocolate offenders" - were disqualified from a much larger study looking at the effects of aspirin on blood platelets. The Genetic Study of Aspirin Responsiveness (GeneSTAR) was conducted at johnd Hopkins from June 2004 to November 2005 and enrolled more than 500 men and 700 women participants nationwide.

Shortly before aspirin dosing began for the subjects, they were told to stay on a strict regimen of exercise and to refrain from smoking or using foods and drinks known to affect platelet activity. These included caffeinated drinks, wine, grapefruit juice - and chocolate.

The non-compliers - who admitted to eating chocolate - were a diverse group who got their flavonoid "fix" from a variety of sources, including chocolate bars, cups of hot cocoa, grapes, black or green tea, and strawberries. And while they were excluded from the aspirin study, Becker and her team scoured their blood results for chocolate's effect on blood platelets, which the body recycles on a daily basis.

When platelet samples from both groups were run through a mechanical blood vessel system designed to time how long it takes for the platelets to clump together in a hair-thin plastic tube, the chocolate lovers were found to be less reactive, on average taking 130 seconds to occlude the system. Platelets from those who stayed away from chocolate as instructed clotted faster, at 123 seconds.

In another key test of urine for waste products of platelet activity, primarily urinary thromboxane (11-dehydro-thromboxane B2), scientists found that chocolate eaters showed less activity and waste products on average, at 177 nanograms per millimol of creatinine, versus an average of 287 nanograms per millimol of creatinine in the group that abstained.

Participants ranged in age from 21 to 80; 31 percent were black and the rest were white. In total, more than 200 different tests of platelet reactivity were performed and analyzed in the study. Because whole blood contains other cells that affect platelet aggregation, testing was repeated using a purified version of test samples made up of strictly platelet-rich plasma.

None of the "offenders" had previous histories of heart problems, such as a heart attack, but all were considered to be at slightly increased risk of heart disease because of family history. Fifty percent of women participants were postmenopausal.

"These results really bring home the point that a modest dietary practice can have a huge impact on blood and potentially on the health of people at a mildly elevated risk of heart disease," says study co-author Nauder Faraday, M.D., an associate professor at Johns Hopkins. "But we have to careful to emphasize that one single healthy dietary practice cannot be taken alone, but must be balanced with exercise and other healthy lifestyle practices that impact the heart."

Johns Hopkins Medicine
Media Relations and Public Affairs

FOR IMMEDIATE RELEASE

ADULT PIG STEM CELLS SHOW PROMISE IN REPAIRING ANIMALS' HEART ATTACK DAMAGE
(Oral presentation #732, Room E354b, Chicago Convention Center)

Johns Hopkins scientists have successfully grown large numbers of stem cells taken from adult pigs' healthy heart tissue and used the cells to repair some of the tissue damage done to those organs by lab-induced heart attacks. Pigs' hearts closely resemble those in humans, making them a useful model in such research.

Following up on previous studies, Johns Hopkins cardiologists used a thin tube to extract samples of heart tissue no bigger than a grain of rice within hours of the animals' heart attacks, then grew large numbers of cardiac stem cells in the lab from tissue obtained through biopsy, and within a month implanted the cells into the pigs' hearts. With help from a blue-dye tracking system, the scientists have shown that within two months the cells had developed into mature heart cells and vessel-forming endothelial cells.

"This is a relatively simple method of stem cell extraction that can be used in any community-based clinic, and if further studies show the same kind of organ repair that we see in pigs, it could be performed on an outpatient basis," says Eduardo Marbán, M.D., Ph.D., senior study author and professor and chief of cardiology at the Johns Hopkins University School of Medicine and its Heart Institute. "Starting with just a small amount of tissue, we demonstrated that it was possible, very soon after a heart attack, to use the healthy parts of the heart to regenerate some of the damaged parts."

Marbán cautions that no overall improvements in heart function have yet been shown in these studies, which were not designed to establish such changes and used relatively low numbers of infused cells (10 million or less). "But we have proof of principle, and we are planning to use larger numbers of cells implanted in different sites of the heart to test whether we can restore function as well," he says. "If the answer is yes, we could see the first phase of studies in people in late 2007."

The latest Johns Hopkins findings are scheduled to be presented Nov. 13 at the American Heart Association's annual Scientific Sessions in Chicago. They are believed to be the first results in animal studies to show that so-called cardiac stem cell therapy can be successfully applied with minimally invasive methods to circumstances closely resembling those in humans. Scientists say the results build on earlier studies with cardiac stem cells in mice and humans that demonstrated success in regenerating infarcted heart muscle and restoring heart cell function post-infarct.

For the study, cardiac stem cells were extracted by tissue biopsy from eight pigs whose main arterial blood supply was tightened for more than two hours, duplicating the effects and damage caused by heart attack.

Using techniques developed in Marbán's lab, researchers extracted about a million cardiac stem cells from undamaged heart tissue, growing them without the use of potentially dangerous chemical stimulators.

After three weeks, the stem cells turned into spherical balls of cells that mimicked the electrical properties of heart muscle cells. The so-called cardiospheres yielded on average more than 14 million cells.

Within a month after the initial heart attack, a catheter tube was inserted into an artery in the pig leg for infusing the cardiospheres. Previous research had shown that they would on their own migrate to the damaged zones of the heart. Marbán's team was able to confirm this because they had labeled the stem cells with a gene that codes for an enzyme producing a blue dye, which could be seen under a microscope.

Months later, when researchers examined the hearts to see if any damaged tissue had been repaired, they found blue spots indicating where the stem cells had taken root.
Closer examination of results revealed that stem cells had matured and grown in the border zones of the damaged area, where researchers suspect both dead and living tissue mingle and some blood supply remains.

"The goal is to repair heart muscle weakened not only by heart attack but by heart failure, perhaps averting the need for heart transplants," says Peter Johnston, M.D., study author and a Reynolds Foundation postdoctoral cardiology research fellow at Johns Hopkins' Heart Institute. "By using a patient's own adult stem cells rather than a donor's, there would be no risk of triggering an immune response that could cause rejection."

Dementia: A generational challenge - baltimore sun
This month, major scientific and medical societies concerned with Alzheimer's disease marked the central event in the evolution of this modern malady: the centennial of the case of Auguste D as presented by Dr. Alois Alzheimer at a medical conference in November 1906.

Something else will not be marked as loudly: The slow but gradual end of Alzheimer's as we know it - and the Americanization of dementia science.
Germany's Alois Alzheimer gave us the basis of the modern conception of the disease, that of a dementia caused by a buildup of plaque between neurons and fibrous tangles inside brain cells. This he did through his examination of Auguste D, 51, who came to him at a hospital at Frankfurt am Main. He found her anxious, disoriented, apathetic, unable to care for herself, often delusional and unable to remember key personal details of her life. As Auguste told Alzheimer at one point: "I have lost myself." Slices of her brain at autopsy showed that her brain had extensive plaque and tangles.

Yet Auguste D's case was hardly tidy. Yes, she had plaque and tangles; no, she did not have brain lesions (dead areas) and artery problems normally associated with brain dysfunction.

For a century, most of neuroscience used Alzheimer's observations to, essentially, reason backward. What causes the tangles, which seem to starve brain cells? What causes the plaque, which seems to mix up neural communication? And how do such changes lead to dementia? The focus on plaque and tangles has led to important discoveries about how brain disease develops, including inflammation, infection, chromosomal aging and beyond. But that narrow focus also has yielded no major therapeutic advances.

In many ways, it took Ronald Reagan, a perpetually sunny Californian, to wrest the disease from the grim determinism of fin de siècle Germany's model of Alzheimer's. The late president's candor about his condition, and his wife Nancy's energetic dedication to the cause, helped transform dementia science. The result is a number of new approaches that, while more promising than classic plaque-and-tangles theory, require a leap of faith. Stem cells are one such tack. If you can grow new neurons, you might be able to rewire demented brains.

More radical: What, for example, if one abandoned "reasoning backward" from plaque and tangles altogether? That is the bombshell dropped last summer in the journal Alzheimer's & Dementia. After studying Alzheimer's patients who were given experimental doses of the diabetes drug Avandia, Allen D. Roses, head of the neurological drugs lab at GlaxoSmith- Kline, and Ann M. Saunders theorized that what causes Alzheimer's dementia is not plaque and tangles. Instead, the disease may result from a "dysfunction" in the way brain cells of a certain genetic stripe use glucose, leading to destroyed dendrites, neurons' main way to communicate. Mr. Roses did not leave the implications of his theory hanging. Targeting impaired glucose - not plaque and tangles - should be a priority for early detection and treatment.

On the other end of the new research wave are academic entrepreneurs who are asking: Can we find a public health intervention that can slow the growing dementia rates in large populations? To that end, the National Institutes of Health have begun trials on omega-3 oils.

A number of promising experiments are under way, including the work of Greg Cole, a professor of medicine and neurology at the University of California, Los Angeles, on the use of curcumin, a spice in curry powder, and its ability to retard dementia-linked changes in Alzheimer's-prone rats. The University of Southern California has a number of experiments under way as well, many inspired by the pacesetting work of Caleb Finch, arguably the world's leading gerontological thinker.

Instructively, dementia and cognitive impairment, not Alzheimer's, have been the hot topics at the major Alzheimer's conventions in recent years. And for good reason. Not all dementia is caused by plaque and tangles (stroke is a leading cause), and not all plaque and tangles lead to dementia. Aging does not inevitably lead to dementia either.MORE - baltimore sun

Certain Fatty Acid May Cut Dementia Risk - washingtonpost.com
Martha Clare Morris is an epidemiologist at Rush University Medical Center in Chicago and author of an accompanying editorial in the journal. "This is the first study to link blood levels of DHA to protection against Alzheimer's disease," she said, adding that recent animal studies have shown that DHA reduces amyloid plaques -- a hallmark of Alzheimer's -- in the brain and also improves memory.

"There is a lot of animal and biochemical evidence to support what this new study shows," Morris said.

But, she said, she's not sure there is enough data to suggest the value of fish oil supplements. "It looks like the protective benefits from omega-3 fatty acids are at a very low level. There is very little evidence that you get better protection from higher intake," she said. "Whether fish oil supplements are protective is yet to be seen."

Another expert thinks clinical trials are needed to see if DHA really protects against Alzheimer's.

"This shows in a prospective study that DHA is the only plasma lipid to cut the risk for developing dementia a decade or more later," said Greg M. Cole, a neuroscientist at the Greater Los Angeles VA Healthcare System and associate director of the Alzheimer's Disease Research Center at UCLA's David Geffen School of Medicine.

This apparent protection is associated with eating fish, Cole said. "Other studies have pointed to fish intake as protective but have been far less clear that the omega-3 fatty acids in fish were the factor associated with risk reduction," he said. "This matters because if it is the fat, you could take fish oil supplements and avoid mercury contamination issues."MORE - washingtonpost.com

Eisai, Pfizer to Ask for U.K. Review of Drug Decision
Eisai Co. and Pfizer Inc. plan to seek judicial review of a decision by a U.K. panel that assesses the cost effectiveness of health treatments, the first such challenge to the agency's authority.

The companies said they notified the panel, the National Institute for Health and Clinical Excellence, that they will ask a court to examine last month's decision not to recommend their Aricept medicine for mild Alzheimer's disease. NICE has 14 days to respond before the case can be filed, the drugmakers said in a statement today.

The appeal would represent the first time a company has legally contested a decision since the panel was established in 1999, NICE spokeswoman Sarita Tamber said today in a telephone interview. The agency's rulings influence what doctors prescribe and what local health authorities in England and Wales fund. The process NICE uses to determine a drug's cost-effectiveness is unclear and unfair, Eisai and Pfizer said in a statement.

``They have not allowed us access to a working model so we can check our own conclusions within that,'' Paul Hooper, managing director of Eisai's U.K. unit, said today in an interview broadcast on the British Broadcasting Corp.'s Radio 4 ``Today'' program. ``This is a secret calculation.''

NICE said on Oct. 11 that Aricept, along with Johnson & Johnson's Razadyne and Novartis AG's Exelon medicines, didn't ``make enough of a difference'' for it to recommend their use in all stages of Alzheimer's disease. The agency will recommend use of the drug in patients with more advanced forms of the disease.

Tokyo-based Eisai and New York-based Pfizer are asking that the panel its decision, postpone the Nov. 22 publication of the guidance, and develop a new model for judging the cost- effectiveness of a drug.....MORE

New Alzheimer's Drug
Doctors are hoping a unique herb could mean hope for the estimated four million people suffering with Alzheimer’s.

A new drug called Huperzine-A could help prevent or delay the symptoms of the disease. Alzheimer’s specialist Dr. Charles DeCarli said although the drug is new the herb has been used for quite some time.

"It is very safe, it has a long history of being used in China where it was discovered."

Dr. DeCarli is conducting a clinical trial of the drug through U.C. Davis’ Alzheimer’s Center. He said some patients are able to tolerate the natural herb better than currently used Alzheimer’s drugs.

No Heart Risk for Women Who Favor Protein Over Carbs - MedPage Today
Women who say no to carbs, but yes to protein as recommended in the South Beach and Zone diets, do not increase their risk of coronary heart disease, according to researchers here.

And women who consume low-carbohydrate diets that emphasize vegetables rather than animals as the source of protein and fat may be rewarded with a moderate reduction in risk of heart disease.
Women whose diets consisted mainly of vegetable protein and fat were are about 30% less likely to develop coronary heart disease than women who whose diets contained either more carbohydrates or more animal protein and fat (P for trend=0.002), Thomas L. Halton, Sc.D. of the Harvard School of Public Health, and colleagues reported in the Nov. 9 issue of the New England Journal of Medicine.MORE

Age and Chronic Illness May Obviate Colorectal Cancer Screening - CME Teaching Brief
There comes a time in life when there is little point in screening for colorectal cancer, researchers here said.

Patients ages 67 and older who have three or more coexisting chronic diseases may not benefit from screening because of shortened life expectancy, reported Cary P. Gross, M.D., of Yale, and colleagues, in the Nov. 7 Annals of Internal Medicine.

In their analysis of the Surveillance, Epidemiology, and End Results (SEER) data and Medicare claims, they evaluated 35,755 patients ages 67 and older.

The researchers found that having three or more chronic illnesses decreased life expectancy to only five to six years for patients in their early 70s at diagnosis, which was the tipping point for a survival benefit from screening.

Randomized trials have suggested the mortality benefit of screening does not become noticeable until five years after screening. Finding and treating colorectal cancer in patients with less than a five-year life expectancy will therefore be useless in extending life, Dr. Gross and colleagues said.

"Screening patients with a life expectancy of less than five years after diagnosis is unlikely to extend their lives," the researchers said.

However, median survival should not be the only consideration in the decision to screen patients for colorectal cancer, said David Casarett, M.D., M.A., of the University of Pennsylvania in Philadelphia, in a related editorial.

"One should elicit the patient's goals for care and expectations about a desirable quality of life, which should influence treatment decisions if cancer was discovered," Dr. Casarett wrote.

Dr. Gross and colleagues found life expectancy was strongly related to both age and burden of chronic illness, particularly for the 26.1% of patients with stage I cancer at diagnosis.MORE

Men With Osteoporosis: More Common Than You Think....Cleveland Clinic

You hear the term osteoporosis, and certain thoughts come to mind: calcium, broken bones … women. Yet osteoporosis -- a disease that lessens bone density, making bones more susceptible to fracture -- affects both genders.

According to the U.S Surgeon General’s 2004 report on osteoporosis, 10 million people over the age of 50 in the U.S. have osteoporosis, and another 34 million are at risk of developing the disease. Of those 10 million, 8 million are women and 2 million are men.

Because post-menopausal Caucasian women are at the highest risk for developing osteoporosis, we tend to associate the disease with women, explains Cleveland Clinic rheumatologist John J. Carey, M.D. Since men do not go through a similar hormonal change, their bone density loss is more gradual and may not be as obvious.

“Men are one of these under-recognized and under-treated groups,” says Dr. Carey. “We know men with osteoporotic fractures are less likely to be treated than women. And we know men have a worse prognosis following a fracture than women.” Indeed, approximately 25 percent of men die within the year following a hip fracture, compared to 15 to 20 percent of women.

So it’s just as important for men to know what increases a person’s risk of developing the disease, as well as how to prevent and treat it. Beyond genetics, other important factors in the development of osteoporosis include poor nutrition, certain medical conditions and medications, and lack of exercise.

Osteoporosis mostly commonly is diagnosed when someone has already suffered a fragility fracture -- a broken bone that occurs from force that is equal to or less than that sustained from a fall from a standing position -- or by taking a bone density test. Unfortunately, men are less likely than women to get this test.

“Of the men who have a hip fracture, only somewhere between 10 to 20 percent actually get referred for a bone density test,” says Dr. Carey. “In women, the number is quite a bit higher, more like 50 to 60 percent.”

It’s vital that men, as well as women, discuss their bone health with their physicians, because there is much that can be done to prevent and treat osteoporosis. Current treatments can slow down or halt your loss of bone and, in some cases, even build up additional bone density. And the same lifestyle changes used to prevent osteoporosis also are beneficial for its treatment.

Are you at risk? You could be at risk for osteoporosis if you:

have suffered a fracture after the age of 50
have a first-degree relative who has osteoporosis or has suffered a fragility fracture
are underweight
have a low intake of calcium
have vitamin D deficiency
drink caffeine in excess (more than 3-4 cups of coffee per day)
take certain medications that can affect bone density, particularly corticosteroids or treatments for prostate cancer
suffer from certain conditions, including endocrine disorders, gastrointestinal diseases, kidney disorders and low testosterone production
have a sedentary lifestyle
smoke
drink alcohol excessively

How to prevent osteoporosis

Eat a balanced diet rich in calcium and vitamin D
Participate in weight-bearing exercises (such as running, walking, yoga and cycling)
Don’t smoke
Drink alcohol in moderation
Reduce your risk of falling
Talk to your physician regularly about your bone health, and take a bone density test and medication when appropriate

Lower Income Means Higher Risk for Heart Disease: USC PRESS RELEASE
Protein linked to heart disease found to be more prevalent in low-income people, minorities and women. Findings may help explain why the poor age faster, say USC and UCLA researchers.

Low-income adults are more likely to have very high levels of C-reactive protein (CRP), a risk factor for heart disease, according to a study led by researchers at the University of Southern California.

The study, published in the current issue of Brain, Behavior and Immunity, finds that among adults with income levels at or below the poverty line, 15.7 percent had very high levels of CRP, compared to only 9.1 percent of those in families above the poverty line.

"We have long known that poor people have worse health," said Eileen Crimmins, corresponding author and professor in the USC Leonard Davis School of Gerontology. "This paper provides evidence that people living at or near the poverty line are almost twice as likely to have very high CRP, which poses risks for long-term, chronic conditions like heart disease and cognitive loss. This may be one of the explanations for why poor people age faster."

CRP is produced as part of the immune response to inflammation. In healthy individuals, CRP levels return to normal after infection or injury subsides. However, some people have chronically elevated levels of CRP. Recent studies have shown high levels of CRP to be a useful predictor of heart disease.

Recent illness, chronic conditions and lifestyle account for some but not all of the explanations for the association between high CRP levels and socioeconomic standing.

"We found that even after accounting for various risk factors, people in poverty still had higher CRP," said Dawn Alley, another corresponding author and a recent doctoral graduate from the USC Davis School. "This suggests that even beyond issues like health behaviors and chronic conditions, there is something about poverty that makes people sick, and at least part of this effect is working through CRP."

The study also found that African Americans, Hispanics and women are more likely to have high levels of CRP, and that obesity is the largest contributor to above normal CRP levels.

The findings, which were funded by the National Institutes of Health, provide a better understanding about risk factors for poor health outcomes later in life.

The Division of Geriatrics at the UCLA School of Medicine also contributed to the study.

Time to Take Another Look at Medicare Drug Plans - New York Times
Maybe you already signed up for Medicare Part D, the prescription drug benefit plan, and maybe you didn’t. Either way, experts strongly urge that every Medicare recipient take a second look.

Enlarge This Image

Stuart Bradford
Those already in a plan may want to consider changing plans during the next sign-up period, Nov. 15 through Dec. 31. Those who are still on the fence about whether to join a plan may want to enroll now, before the penalties for delayed enrollment increase significantly.

Though legislation is pending in Congress to drop the premium penalties, at least for this first year, they are still in place and amount to 1 percent of the average national monthly premium for each month that you didn’t sign up.

If you haven’t yet signed up and do so in November, you will pay a premium penalty of 7 percent — 1 percent for each month since May. If you wait a year, the premium penalty will be 19 percent, and the average national premium may be higher as well. Furthermore, these penalties are not a one-time matter; they will stay with you as a higher monthly premium for as long as you are in a Part D plan.

People who currently have drug benefits through other insurance plans should not join a Part D plan unless it is much better than their current coverage.

They will not be penalized for joining a Part D plan at a later date unless they lose their current benefit and fail to sign up for a Medicare plan at the next opportunity. Deane Beebe of the Medicare Rights Center, a nonprofit advocacy group in New York, pointed out that people with drug benefits through a non-Medicare plan risked forfeiting their current coverage if they signed up for a Part D plan.

Some Problems

There are two main problems with Part D:

1) There are far too many choices. California, for example, has 55 stand-alone prescription drug plans, not counting dozens more in individual counties. Each plan has its own premium, its own formulary for the drugs it covers, its own deductible and its own copayments for individual drugs. Anyone taking half CLICK FOR FULL STORY - New York Times

Tyler Morning Telegraph - A HUSBAND'S MEMORY FADES IN BATTLE WITH ALZHEIMER'S , BUT NOT A WIFE'S LOVE
Sue and Paul Kiely have been married for 24 years. Paul was diagnosed with Alzhe-imer’s disease five years ago, and now relies on his wife to take care of him.(Photo by AMY PETERSON)

Homer would not wax poetic for Paul and Sue Kiely. Nor would Shakespeare immortalize their relationship with searing drama. Neither would Keats devote reams of paper to quiet, tragic triumph of their marriage.
Great love stories may have more pomp and fire than their 24 years together, but that does not render Mrs. Kiely's tireless devotion to her husband any less poignant, any less bittersweet, or any less romantic.
It's fetching him a glass of water when he doesn't realize he hasn't drunk in four hours. Or sitting in the next chair while he relentlessly reads aloud every line of a medical ad. Or gently showing him the wedding pictures when he can't remember that she is his wife.

"We had a great love affair," said Sue Kiely. "I just can't walk away from that."
From the first time he lost a memory to the first time he thought men were hiding in their attic, she has stayed at his side. Now in his fifth year battling Alzheimer's disease, Kiely cannot function on his own, his brain eroded by the degenerative disorder which afflicts millions across the globe.
And even though his wife has lost her companion, her confidante, her intellectual partner and the love of her life, she gets out of bed every day to live with, care for and even dote on her husband.
FOR A MOMENT
Five years ago, Kiely was saddened but healthy, reeling from the loss of his daughter to leukemia. When the Kielys arrived at his other daughter's house after the funeral, he glanced at his wife and asked, "How did we get here?"
"I attributed it to stress," Mrs. Kiely remembers. "A moment of forgetfulness that was quite pronounced. Then
more

Changing minds in Alzheimer's research - Los Angeles Times Opinion Page
Scientists have moved away from plaque and tangles in the brain toward developing better treatments for the disease.
By Greg Critser, GREG CRITSER, the author of "Fat Land and Generation Rx,"

THIS WEEK, major scientific and medical societies concerned with Alzheimer's disease are marking the central event in the evolution of this modern malady: the centennial of the case of Auguste D as presented by Dr. Alois Alzheimer at a medical conference in November 1906.

Something else will not be marked as loudly: the slow but gradual end of Alzheimer's as we know it — and the Americanization of dementia science.

It was Alois Alzheimer who gave us the basis of the modern conception of the disease, that of a dementia caused by a buildup of plaque between neurons and fibrous tangles inside brain cells. This he did through his examination of a 51-year-old woman named Auguste D, who came to him at a hospital at Frankfurt am Main. He found her anxious, disoriented, apathetic, unable to care for herself, often delusional and unable to remember key personal details of her life. As Auguste told Alzheimer at one point: "I have lost myself." Slices of her brain at autopsy showed that Frau D's brain had extensive plaque and tangles.

Yet Auguste D's case was hardly tidy. Yes, she had plaque and tangles; no, she did not have brain lesions (dead areas) and artery problems normally associated with brain dysfunction.

For a century, most of neuroscience used Alzheimer's observations to, essentially, reason backward. What causes the tangles, which seem to starve brain cells? What causes the plaque, which seems to mix up neural communication? And how do such changes lead to dementia? The focus on plaque and tangles has led to important discoveries about how brain disease develops, including inflammation, infection, chromosomal aging and beyond. But that narrow focus also has yielded no major therapeutic advances.

In many ways, it took a presence like Ronald Reagan, a perpetually sunny Californian, to wrest the disease from the grim determinism of fin de siècle Germany's model of Alzheimer's. The late president's candor about his condition, and wife Nancy's energetic dedication to the cause, helped transform dementia science. The result is a number of new approaches that, while more promising than classic plaque-and-tangles theory, require a leap of faith. Stem cells are one such tack. If you can grow new neurons, you might be able to rewire demented brains.

More radical: What, for example, if one abandoned "reasoning backward" from plaque and tangles altogether? That is the bombshell dropped last summer in the pages of the journal Alzheimer's & Dementia. After studying Alzheimer's patients who were given experimental doses of the diabetes drug Avandia, Allen D. Roses, head of the neurological drugs lab at GlaxoSmithKline, and Ann M. Saunders theorized that what causes Alzheimer's dementia is not plaque and tangles. Instead, the disease results from a "dysfunction" in the way brain cells of a certain genetic stripe use glucose, leading to destroyed dendrites, neurons' main way to communicate. Roses did not leave the implications of his theory hanging. Targeting impaired glucose — not plaque and tangles — should be a priority for early detection and treatment.

On the other end of the new research wave are academic entrepreneurs who are asking: Can we find a public health intervention that can slow the growing dementia rates in large populations? To that end, the National Institutes of Health has begun trials on omega 3 oils. But it is California — and particularly Los Angeles — that is at the leading edge of such work.

A number of promising experiments are underway, including the work of Greg Cole, a professor of medicine and neurology at UCLA, on the use of curcumin, a spice in curry powder, and its ability to retard dementia-linked changes in Alzheimer's-prone rats. USC has a number of experiments underway as well, many inspired by the pacesetting work of Caleb Finch, arguably the world's leading gerontological thinker.

Instructively, dementia and cognitive impairment, not Alzheimer's, have been the hot topics at the major Alzheimer's conventions in recent years. And for good reason. Not all dementia is caused by plaque and tangles (stroke is a leading cause), and not all plaque and tangles lead to dementia. Aging does not inevitably lead to dementia either.

Where gerontological wisdom once held that anyone who lived to 110 or older would be demented and/or afflicted with plaque and tangles, such has turned out not to be the case. Jeanne Calment, the Frenchwoman who lived to age 121, was cognitively unimpaired to the end. And gene science and brain scanning are showing that dementia is hardly the linear disease that Alzheimer and his successors proposed. Environment catalyzes genes, genes catalyze environments. Reagan's dementia has become a hot topic among researchers for this reason. What role did the environment created by his neglectful alcoholic father and emotionally absent mother play in the origins of his disease? Did the fact that he was easily able to quit smoking indicate a shortage of certain, later critical, brain receptors?

But whether caused by plaques, tangles, genes or childhood experience, there is clearly a huge dementia wave coming. We as a society are getting older, and we are doing so in a uniquely American way — as big-time consumers of fat, sugar, booze and drugs — legal and illegal. And so the boomer pattern of neural aging slowly but surely emerges. Boomers might come in with "normal aging issues," said Annette Swain, a San Fernando Valley clinician. "But on closer examination, they have a significant 'other' problem — the untreated diabetic with brain issues because of uncontrolled blood sugar. Or long-term pot users — in their 50s and early 60s — who are utterly puzzled by the fact that they have slower reaction times. The same with alcohol abuse and bad eating patterns, or improper use of prescription drugs."

She pauses. "What they don't seem to get is that it matters how you've lived your life."

Instead, the boomer ethos has turned to — what else? — gadgets and games, Sudoku and Brain Age. It's true that such brain teasers can impart small increments of "cognitive reserve," and they're fun. But they hardly address the real issues. "I am afraid we are going to get into the habit, you know, of sitting around the pool and debating whether Sudoku or Brain Age is better for making our brains healthier, while as a society we resist dealing with real medical issues and their detection, everything from mild cognitive impairment to dementia," said J. Wesson Ashford, who sees demented patients at the Stanford/VA Alzheimer's Research Center of California. "Only about one-half of dementia patients are ever diagnosed as such. We have got to get better at that."

To do so, Ashford and his colleagues recently issued an international call for annual screening for dementia in people older than 75, and a baseline "dementia discussion with your physician" at age 50. It is a bold initiative, considering that there is no treatment for Alzheimer's. It is also a generational challenge. Ashford believes that the benefits of anxiety reduction for those who discover they are not at risk, along with risk reduction and symptom reduction for those who are, are worth it.

The response to his call? "So far, there's really only one word," he said. "Apathy." It's a symptom worth attending to. Do it for the Gipper.