Smithsonian.com

What a deteriorating brain looks like. Image courtesy of National Institute on Aging

It’s been called the holy grail of medical research, a discovery that could profoundly change what it means to grow old. The personal costs of Alzheimer’s disease to its victims, and the family and friends who have to watch its insidious assault on their loved ones, is enormous.

The financial costs are equally staggering. The cost of caring for the more than 5 million Americans with Alzheimer’s–there are 35 million worldwide–already is estimated to be $200 billion a year. By 2050, it’s expected to top a trillion dollars.

But the search for a treatment that cures Alzheimer’s, or even slows it down, has not gone well. Over the past 20 years drug companies have seen one trial after another end in failure. Nothing, it seemed, could kill the beast. Two more big studies of new drugs–one developed by Pfizer and Johnson & Johnson, the other by Lilly–will be completed this fall. And while the drugmakers hope that this time they’ve found an answer, there’s been much speculation that if they haven’t, they may throw in the towel.

Earlier this week, though, thousands of the world’s leading Alzheimer’s researchers and experts at an international conference in Vancouver, heard some heartening news for a change. A cure for Alzheimer’s remains as elusive as ever, but scientists seem to be making headway in slowing down the horrific mental deterioration that makes the disease so terrifying.

In one study, for instance, researchers were able to stabilize the conditions of four Alzheimer’s patients for three years. That may not sound like much–only 16 people were in the study–but any indication that the downward spiral could be stopped offers no small promise. The four patients who didn’t decline mentally were the only ones in the study who received the same dosage of the same drug–an intravenous immune system treatment called Gammagard–for all three years.

Whether or not this turns out to be another splash of false hope won’t be known until a larger trial is completed next year. And even if the results are positive, plenty of challenges would remain, including the cost. In its current form, Gammagard, created by Baxter International, costs between $3,000 and $6,000 a month.

Preventive medicine?

While the Gammagard research involves patients already reflecting the effects of Alzheimer’s, another proposed study, announced at the conference, would focus on people who are showing no symptoms, but who have an abnormal protein in their brains believed to be an indicator of the disease.

Most Alzheimer’s experts now believe the reason attempts to fight it with drugs haven’t succeeded is that they’ve been started too late. It’s thought that more than 50 percent of critical brain cells are already lost by the time a patient displays even mild cognitive impairment.

So the key may be to battle the disease long before it makes its presence known. In fact, according to an Alzheimer’s timeline developed at Washington University Medical School in St. Louis, the first effects can be detected in the body 25 years before the onset of cognitive decline.

To see if drugs can be more effective on people who haven’t yet been formally diagnosed with Alzheimer’s, the planned study will involve 1,000 people over the age of 70 who have buildup of amyloid beta plaques in their brains but have shown only a minor loss of cognitive skills.

Half of the participants will be given a still-to-be-determined drug, the other half a placebo. They also will be provided with counseling to reassure them that having amyloid in their brains doesn’t guarantee that they’ll develop Alzheimer’s. The Boston scientists who would do the research won’t know until this fall if they’ll receive the federal funding they need.

A low risk mutation

Just before the conference, there was more positive news. A study published a week ago in the journal Nature by a team of Icelandic researchers identified a genetic mutation that greatly reduces a person’s risk of getting Alzheimer’s.

The scientists found that people with the mutation, which is very rare, produced about 40 percent less of the proteins that become the amyloid plaques linked to Alzheimer’s and other memory loss. For some researchers, this confirms that plaques are the culprit. Rudolph Tanzi, of Harvard Medical School and a scientist who helped discover the gene mutation, thinks a path has been drawn.

He believes researchers need to attack amyloid plaques as aggressively as heart disease experts have gone after high cholesterol.

“We’ve got to have that same focus with Alzheimer’s disease,” he told NPR, “and I’m hoping that this paper will galvanize us to say, ‘OK, this is our target.”

Cause and effects

Here’s more that recent research has learned about Alzheimer’s:

• Both too little and too much sleep can raise your risk of Alzheimer’s. A study of 15,000 women 70 or older had worse brain functioning if they typically slept five hours or nine hours a night than women who averaged seven hours a night.The researchers also discovered that if the amount of time a woman slept changed by two or more hours per day as she progressed from mid-life to old age, her brain functioning deteriorated more than those who didn’t change their sleep patterns.
• So does binge drinking. People 65 and over who say they binge drink at least twice a month are two and a half times more likely to suffer cognitive declines than those who don’t drink that much. Binge drinking, as defined for this research, is consuming four or more drinks on one occasion.
• If your walk is slower, so’s your brain. A number of studies presented at the conference concluded that an older person’s slowing gait can reflect a parallel decline in memory and thinking skills.
• Pumping iron can help stave off dementia. While all exercise helped women between 70 and 80 hold on to their memory and cognitive skills in several studies, those who did strength training–lifting weights or using resistance bands–seemed to benefit the most.
• Soon you could be screened for Alzheimer’s with a blood test. Two separate reports published in the Archives of Neurology say that markers have been found in blood that distinguish those with Alzheimer’s from those who don’t have it. Currently, testing is both expensive and invasive–it involves brain scans and spinal punctures.

Video bonus: Enough with all this talk about memory loss. Take a break and watch how a “World Memory Champion” trains his brain. Be very jealous.

More from Smithsonian.com

The Race for an Alzheimer’s Miracle

Building a Human Brain

Is there an end in sight for Alzheimer's? Image courtesy of Flickr user Susan NYC

If you made it through the Grammy Awards Sunday night, you probably saw onetime country pop star Glen Campbell. And you may know that, like almost every singer who had a few hits in the 1970s, Campbell’s in the middle of a farewell tour.

But this isn’t some Rolling Stones’ “I-can-still-dance-and-wear-tight-pants” spectacle. This is a real Farewell Tour. Because Campbell, now 75, has Alzheimer’s disease. And it won’t be long before he won’t remember lyrics or how to play the songs he’s performed thousands of times. Then things will get considerably worse.

In a perfect world every Alzheimer’s patient would get a farewell tour, a chance to make one last sweep through a life before all the names and connections and memories get locked away inside a shuttered brain. But most don’t, and instead disengage from the world as their family and friends watch, with no way to slow the cruel decline. Right now there are more than 5 million people with Alzheimer’s in the U.S. alone, with that number expected to triple by 2050.

Unless…

Researchers discover a miracle drug that stops the downward spiral before it gets started. There’s been talk of this for years now, suggestions that scientists were getting close. It hasn’t happened. But just last week hopes were raised again with the report that researchers at Case Western Reserve in Ohio had made a remarkable discovery. After treating mice with a drug called bexarotene, usually a treatment for skin cancer, they found that, within 72 hours, the animals were able to start remembering things again.

The news set off a frenzy of calls to doctors from people anxious to know if this really was some magic cure. Could it actually reverse the horrible effects of Alzheimer’s on humans?

No one knows yet. It’s entirely possibile it will have little or no effect.  The scientists at Case Western hope to start a  small trial on humans this spring, which could last four months. But after that it’s hard to say how this will play out because the patents on bexarotene as a cancer drug, held by the Japanese pharmaceutical firm Eisai, Inc., run out this year and so far it hasn’t shown interest in funding the new research at Case Western.

Meanwhile, two other big pharmaceutical firms, Pfizer, Inc. and Eli Lilly will have data from trials on their own Alzheimer’s drugs later this year. Talk about high stakes–particularly for Pfizer, which badly needs a big seller, now that the patent on Lipitor, its cholesterol medication that was a cash cow for so many years, has run out. Can you imagine what it will mean to be first on the market with a truly effective Alzheimer’s treatment?

Darkness spreads

Two other discoveries announced this month, while not quite as dramatic as the bexarotene study, could be almost as pivotal in finding an effective treatment. The first, confirmed in separate studies at Harvard and Columbia, found that Alzheimer’s spreads from neuron to neuron along paths that nerve cells use to communicate with one another. And that suggests that one way to stop the disease would be to find a way to prevent cell-to-cell transmission.

In the other key finding, UCLA scientists determined that a brain imaging tool they developed could effectively track the buildup of memory-dimming plaque deposits in the brain, which could allow treatment to begin even before symptoms appear.

Consider them two more pieces that may help solve the nastiest brain puzzle of all.

Brain drains

Here’s more recent news on memory research:

• Shocking news: Researchers at UCLA found they were able to improve memory by using electrical stimulation on the part of the brain where the first signs of damage from Alzheimer’s usually appear.
• Forget how to count calories? Older people who consume more than 2,000 calories a day could double their risk of memory loss. That’s what scientists at the Mayo Clinic concluded after a study of 1,200 men and women in their 70s and 80s.
• Another reason not to wake me up: More evidence of the value of a good night’s sleep comes from researchers at the Washington University School of Medicine in St. Louis.  They determined that there may be a link between “disrupted sleep” and the buildup of amyloid plaque in the brain, a marker of Alzheimer’s.
• Is 40 the new 60? A recent study in London found that cognitive function could actually start declining in people as young as 45.
• There’s an app for that? Yes, there now actually is a Facebook app, created in Singapore, that allows you to experience Alzheimer’s disease. It’s called Sort Me Out and it’s designed to give you a sense of what it feels like to lose your friends and memories.

Video bonus: Neuroscientist Daniel Wolpert thinks we give our brains too much credit.  In this TED talk, he argues that their real purpose is not to let us think, but rather to help us move.