PET scans peer into the heart of dementia

There’s no question that tests to detect cancer before it causes any problems can save lives. But such tests can also cause harm through overdiagnosis and overtreatment.

A study published online yesterday in JAMA Internal Medicine indicates that the majority of people are never informed by their doctors that early warning cancer tests may detect slow-growing, or no-growing, cancers that will never cause symptoms or affect health. Undergoing surgery, chemotherapy, or radiation for such cancers provides no benefits and definite harms.

The study authors, both at the Max Planck Institute for Human Development in Berlin, did an online survey of 317 men and women in the United States. They ranged in age from 50 to 69 years, the age range when people generally undergo cancer screening tests. The survey asked if a physician had told them about the possibility of overdiagnosis and overtreatment, an online survey to find out how many had been told by their doctor about the possibility of overdiagnosis and overtreatment. It also tried to gauge how much overdiagnosis the participants would see as okay when deciding to have or reject cancer screening.

The researchers found that only 9.5% of people were informed of the risk of overdiagnosis and possible overtreatment when discussing cancer screening with their doctors. Compare that with 80% who said they wanted to be informed of the possible harms of screening before having a screening test.

Informing patients about the risks of screening isn’t easy to do in a brief office visit. It’s complicated information. And the researchers suggest that many doctors don’t have a good grip on relative benefits and harms of screening. They cite a study showing that barely one-third of U.S. doctors were able to provide correct estimates for the extent of overdiagnosis for mammography (breast cancer screening) and PSA testing (prostate cancer screening).
Testing differences

Of the common cancer screening tests, experts disagree most about mammography and PSA testing. A mammogram every year or other year for women age 50 and older has broader acceptance. But some studies suggest that the life-saving benefits of mammography are overstated. And doctors rarely discuss the risks of finding spots that aren’t cancer or spots that are cancerous but would never have cause harm before they recommend yearly mammograms.

PSA testing is even more controversial. Once widely recommended, the general recommendation is now that doctors not order a PSA test without first having a discussion about the pros and cons of testing. The highly respected United States Preventive Services Task Force recommends against screening men at average risk of prostate cancer.

In contrast to breast and prostate cancer screening, checking for colorectal and cervical cancer has more solid evidence behind them. Colonoscopy and cervical cell sampling (Pap tests) not only detect early cancers, but detect polyps and pre-cancers. Removal or other treatment can actually help prevent cancer. Mammograms and PSA tests, by contrast, can only detect early cancers.
Don’t overlook prevention

If your doctor recommends a screening test, ask him or her about the risks as well as the benefits, and to put them in perspective. Then you can make an informed decision about whether the test is something you should have.

Keep in mind that cancer screening is already somewhat tailored to personal risk. People with a family history of certain cancers should start screening at earlier age and get screened more frequently. They also may require different types of tests. In the future, genetic testing will help guide screening recommendations.

The promotion of cancer screening sometimes overshadows the importance of cancer prevention. There are many things you can do to help protect yourself against cancer:

    Maintain a healthy weight.
    Don’t smoke or use other tobacco products.
    Either avoid alcohol or drink an average of no more than one alcoholic beverage per day.
    Avoid binge drinking, even if the average amount of alcohol you drink is moderate.
    Eat a diet rich in vegetables, especially the green leafy ones. They are rich in folic acid. For women, folic acid may offset any increased risk of breast cancer if you drink alcohol.
    Increase your fiber intake. It may lower your risk of colon cancer.
    Stay physically active and try to find time every day for dedicated exercise. Aim for at least 150 minutes of exercise per week.What’s bad for your heart is often bad for your brain. High cholesterol, high blood pressure, diabetes, and unhealthy “hardening” of the arteries increase your risk of mental decline or dementia later in life. A study published online today in Neurology opens a window into how cardiovascular disease affects the brain and may even lead to some important insights into Alzheimer’s disease.

Researchers from the University of Pittsburgh and the University of Virginia found that elderly people with the stiffest arteries were most likely to show the kinds of damage to brain tissue often seen in people with dementia. Although heart-unhealthy lifestyles have been linked to increased risk of Alzheimer’s disease—the most common form of dementia in older adults—the results of this study suggest there may be a silver lining: “This is more evidence that cardiovascular health leads to a healthy brain,” says University of Pittsburgh researcher Timothy Hughes, PhD, the lead author of the study.

In the past, getting a close look at both brain and artery health could only be done in people who had died, since an autopsy is necessary to get samples of brain tissue. The Neurology study provides a view into living brains—and a chance to study the changes that build up to full-blown dementia.

“There have not been many studies that look at amyloid pathology in living people in combination with evidence of vascular disease on imaging to predict development of dementia,” says Dr. Gad Marshall, an assistant professor of neurology at Harvard Medical School and Alzheimer’s researcher at Brigham and Women’s Hospital.
Peeking into brains

Hughes and his fellow researchers conducted a study of 91 elderly men and women, average age 87, still living independently in their communities. Each underwent a special kind of PET brain scan to look for beta amyloid, the sticky protein that collects in the brains of most people diagnosed with Alzheimer’s disease. Deposits of amyloid, called plaque, lead to the devastating changes in mind and memory that are the hallmark of Alzheimer’s disease.

Although none of the participants showed signs of dementia, about half of them had significant amounts of amyloid deposits in their brains. “We did not expect to see so much plaque in so many participants in the study without dementia,” Hughes says.

The study participants also underwent a series of tests for cardiovascular health. One measured arterial stiffness, an indicator of the health of the body’s network of arteries. Most people know arterial stiffness as “hardening of the arteries,” brought on in large part by the effects of high blood pressure and other damage to artery walls. In general, arteries stiffen with advancing age. People with the stiffest arteries were much more likely to show two kinds of changes in the brain:

    More amyloid plaque appeared in PET scans. Such plaque has been linked to Alzheimer’s disease.
    More damage to the “white matter” of the brain seen on MRI scans. White matter is composed of the nerve fibers that shuttle messages between the various brain centers. White-matter damage is a marker of trouble in small arteries responsible for nourishing brain tissue. “The MRI scans were picking up disease in the small arteries of the brain that are likely being caused by vascular disease in the body,” Hughes explains.

Two “hits” to the brain

Besides confirming the ravages of cardiovascular disease on the brain, the study provides some clues that could help solve a longstanding puzzle about the relationship between amyloid protein and Alzheimer’s disease. Many people with significant amounts of amyloid in their brains do not show symptoms of dementia. Yet aging can sometimes nudge them over into dementia. What happens in the brain to make that happen?

One possible answer is known as the “two hit” theory of amyloid and vascular disease. Some research suggests that “amyloid collects in the brain over years and decades until the brain can no longer compensate for it and cognitive impairment begins to set in,” Hughes says. The combination of amyloid deposition and damage to small arteries that nourish brain tissue could, hypothetically, tip the scales. “Amyloid deposition and vascular disease may be the double hit that may really cause a person to convert to dementia.”

That’s speculation right now, but being able to track both amyloid protein deposits and physical damage to the brain over time in living people could get us to an answer—and a powerful way to head off dementia. “Vascular health leads to brain health,” Hughes says. “That’s the big overarching theme here. If the same is true in younger adults, it might give us a way to prevent amyloid deposition in later life.”


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