By Kathleen Fackelmann USA Today
About a decade ago, June Pond noticed that her husband, Marshall, was starting to miss appointments at the travel agency he ran. At first, she thought it was nothing more than forgetfulness for a man in his 70s.
But when the memory lapses continued, she became worried. After a battery of tests, Marshall was diagnosed with an early form of Alzheimer's, a progressive brain disease that begins with mild memory lapses and ends with people unable to recognize their closest relatives.
Currently, there's no proven way to avoid that slide to full-blown dementia. So Marshall Pond enrolled almost two years ago in a preliminary study of a drug that he hopes will prevent his worst nightmare.
The drug is Lipitor, one of a group of prescription drugs called statins that millions of Americans take to lower their cholesterol and their risk of heart disease. Researchers now are testing those same drugs to see if they also lessen the ravages of Alzheimer's.
''I think this must be helping,'' June Pond says. ''People usually go downhill pretty fast.'' Marshall's memory, she says, hasn't worsened. He's able to carry on a conversation with a friend. In fact, most people don't realize Marshall has Alzheimer's at all.
The researcher for the Lipitor study, Larry Sparks of the Sun Health Research Institute in Sun City, Ariz., believes statins may hold the line on Alzheimer's or perhaps prevent it from developing in the first place.
Scientists know that too much cholesterol in the blood can clog arteries in a process that can lead to a heart attack. But many researchers now think that high blood cholesterol also affects the brain.
''Excess cholesterol may be instrumental in the formation of senile plaque,'' Sparks says. That plaque, the hallmark of Alzheimer's, is an abnormal cluster of dead or dying brain cells and toxic proteins that short-circuit memory and other crucial brain functions.
Ten years ago, most researchers simply dismissed the link between cholesterol and Alzheimer's. But that attitude began to change when more than a dozen studies suggested otherwise.
Ongoing research to better define the relationship between the two has the potential to help an estimated 4 million Americans who currently suffer from Alzheimer's. If a cholesterol-lowering strategy can be shown to prevent it, the findings would help millions of baby boomers who face the growing threat of the disease, which can strike people in their 50s but is most common after 65.
The nation desperately needs a preventive strike against this brain disorder, says Bill Thies, a vice president at the Chicago-based Alzheimer's Association. Without it, his group estimates, the number of Americans with Alzheimer's will jump to 14 million by 2050.
''We're on the ascending limb of an epidemic,'' he says.
There's no doubt Alzheimer's disease is a complex illness, one probably caused by genetic, environmental and perhaps other factors. Still, if this new theory pans out, it could mean something as simple as lowering blood cholesterol levels could help reduce the risk of a disease that robs the mind of memories and, in the end, even of rational thought.
The research also gives Americans another reason to lower elevated blood cholesterol levels with a low-fat diet or with drugs.
''If you lower your cholesterol levels right now, you'll be healthier,'' Sparks says, noting that such a step reduces the risk of heart disease and may offer the bonus of warding off Alzheimer's.
More evidence on the cholesterol theory will be presented later this month at the International Conference on Alzheimer's Disease and Related Disorders in Stockholm, Thies says.
In addition, he says, researchers will present findings suggesting that people who take steps to reduce their risk of heart disease, such as eating a healthy diet or reducing blood pressure, can reduce their risk of Alzheimer's.
Similar plaques
In the 1980s, Sparks noticed that people who had died of heart disease had deposits in their brain that looked surprisingly like the senile plaque of Alzheimer's disease.
Sparks knew those people had clogged arteries or atherosclerotic plaque caused by too much cholesterol in the blood. He wondered whether that excess cholesterol also caused a different kind of plaque in the brain.
He did a laboratory study in which he fed rabbits a high-fat, high-cholesterol diet. After eight weeks, he found brain deposits that looked just like the beginnings of Alzheimer's disease.
Results from those studies and others began to jell into a new theory. The evidence suggested that too much cholesterol in the blood somehow got brain cells to dump a toxic protein called beta amyloid. Outside the brain cell, that protein began to clump together to form the senile plaque.
Sparks began to think about testing that theory.
''We've got cholesterol-lowering drugs approved by the FDA, and they're safe,'' he reasoned. ''Let's see if they help treat Alzheimer's.''
Sparks did that by giving Lipitor to about 100 men and women with the earliest stages of Alzheimer's. The findings from that study, which was funded in part by Pfizer, the company that makes Lipitor, won't be in for another year, he says.
Lipitor is one of five statin drugs on the market today; Pravachol, Lescol, Zocor and Mevacor are the others.
New research suggests the statin drugs may also prevent Alzheimer's from developing. The latest and largest study of that connection was done by Robert Green of the Boston University School of Medicine. Green and his colleagues studied 912 people with Alzheimer's and more than 1,600 who did not have the disease.
The researchers looked at each group's medication history and, in particular, whether they had gotten a prescription for a statin drug. They found that the healthy people in the study were much more likely than the Alzheimer's patients to have a history of taking these drugs.
People taking statins reduced their risk of developing Alzheimer's by nearly 80%, says Green, who presented his team's findings in April at the American Academy of Neurology meeting in Denver.
His team also looked specifically at people with the ApoE4 gene, a gene that puts them at risk of Alzheimer's disease. This study found that such people also cut their chances of Alzheimer's by taking statin drugs.
No one knows how this gene increases the risk of Alzheimer's. But scientists do know that people with the ApoE4 gene tend to have high blood cholesterol levels. The elevated cholesterol puts them at risk of heart disease, and it may boost their chance of developing Alzheimer's, Sparks says.
Green's study also showed that statin drugs offered the same shield against Alzheimer's for African-Americans, a group that may be at higher risk of developing the disease.
While Sparks and others see a link between Alzheimer's prevention and lowering cholesterol, researcher David Drachman of the University of Massachusetts-Worcester has an alternative explanation as to why statins may help. He says the drugs also boost the blood flowing to the brain and may offer some protection.
Conclusive proof needed
Moreover, cautions David Knopman, a neurologist at the Mayo Clinic in Rochester, Minn., the study by Green and his colleagues doesn't offer definitive proof that such drugs really stave off Alzheimer's. To get that evidence, scientists will have to do a large clinical trial, one that could take many years to complete, he says.
Still, the statistical link between statin use and reduced risk is strong. ''This association looks very real,'' Green says.
In addition, several other studies suggest these drugs protect against Alzheimer's disease. For example, Canadian researcher Kenneth Rockwood of Dalhousie University in Halifax, Nova Scotia, studied 2,300 people and found that those who were taking statins were 75% less likely to develop Alzheimer's.
Yet, scientists such as Thies of the Alzheimer's Association say it's still too early to recommend that healthy people take cholesterol-lowering drugs solely to ward off dementia.
He says the studies have yet to prove such drugs prevent the disease. And, like all drugs, they have side effects, which include a potentially fatal muscle disorder.
Beyond that, no one knows what the drugs would do if they were given year after year to healthy people.
''We don't know if there are any unexpected side effects,'' Knopman says. ''That's the caution.''
Despite such concerns, Thies and others encourage people who already have Alzheimer's disease to consider volunteering for a study of such drugs.
For Maurine Longstreth and her 78-year-old husband, Harold, of Sun City, Ariz., the unknown risks had to be weighed against a race with time.
He's in the early stage of Alzheimer's and has been taking Lipitor for about a year.
Maurine describes the day-to-day progression of the disease: Harold forgets what he had for breakfast. He has forgotten key moments from their past. And he has gotten lost coming home from the doctor's office.
''I am hoping,'' she says, ''that Lipitor has slowed things down.''
