Issue Date: September 2, 2001

In this article:
Great hope for the future
More on Alzheimer's
A chat with author David Shenk at 3 p.m. ET Tuesday September 4, co-sponsored by usatoday.com.

Alzheimer's:

A Conversation About Memories Lost

The new book "The Forgetting" (Doubleday, $24.95) is David Shenk's bid to focus attention on the epidemic of Alzheimer's disease in the same way Randy Shilts' 1987 book, "And the Band Played On", awakened the nation to the scourge of AIDS. The time is ripe: Baby boomers and younger adults not only tend to afflicted parents, but soon will start entering the demographic themselves as the first boomers reach age 65. Shenk, who spent three years synthesizing "all we know and all we anticipate" about Alzheimer's, began his quest after overhearing two men have an emotional, haunting conversation about the disease.

Personal tragedy brought USA WEEKEND Senior Editor Constance Kurz to the topic. Her mother, Virginia, died of end-stage Alzheimer's in 1998 at age 75, after years of decline.

Shenk and Kurz compare what they've seen and learned about the devastating disease.

Kurz: In your book, you call Alzheimer's "death by a thousand subtractions." Nancy Reagan has called the disease that ravages her husband "the long goodbye." My mother's Alzheimer's felt like a slow, deepening fog, like the Carl Sandburg poem she used to read my sister and me: "The fog comes on little cat feet."

Shenk: One of the profound things I learned is that Alzheimer's is an excruciating long-term disease. It robs us, degree by degree, of the person we love over a period generally recognized to be, on average, eight years.

Yes, that was about the time frame for Mother. My father believed he could pinpoint the weekend -- Easter 1988 -- when he first noticed her repeating herself and losing short-term memory.

One of the interesting things is that we have no idea when the disease actually starts, when the plaques and tangles that are the markers of the disease start to creep into your brain. It's conceivable that you could be accruing plaques and tangles in your 20s, 30s and 40s.

The numbers cited in your book are alarming: In the 1970s the United States had 500,000 sufferers; today it's 5 million. And researchers project triple the number -- 15 million -- by 2050. What's up?

Anyone would wonder: Is there something about modern life that is contributing to these numbers? It turns out the rise is very strictly attributed directly and only to the rise in longevity. Go back 100 years, and the average life expectancy in an industrialized country was in the 40s. So the number of people who lived long enough to get Alzheimer's wasn't enough to attract attention.

Are there predictors of who might get Alzheimer's?

Researchers haven't been able to nail down any significant differences in risk. They have a strong feeling that environmental factors help trigger what is ultimately a genetic condition. But it is not as simple as "If you smoke, you are twice as likely to get Alzheimer's." The only difference worth noting: Women get Alzheimer's slightly more often than men.

If your brain gets a daily workout, does it prevent the disease? Mother was a great reader and loved to travel.

The notion of "use it or lose it" is valid. Scientists say being smart and exercising your mind as vigorously as you can for as long as you can will not guarantee you of escaping Alzheimer's disease, but it may well push it off until later in life. What is unsound is the prejudice that someone with Alzheimer's is not intelligent or lived a lazy-thinking life. It strikes Nobel laureates and brilliant professors and mathematicians and artists and writers and presidents of the United States! I mean, for all the knocks Ronald Reagan got, the guy wasn't dumb.

There is a huge social stigma surrounding this disease that is really ignorance. It's people not understanding Alzheimer's and being really freaked out: "I don't want to be a part of it. Is it contagious?" The only way to get rid of it is to educate people. Even if you don't experience this disease yourself or in your family, you will see it. It's too common to miss.

Can you explain what's happening in the Alzheimer's brain -- the difference between plaques and tangles?

Sure. Alzheimer's, since German doctor Alois Alzheimer identified it in 1906, has been recognized to be a disease in which two major foreign invaders come into the brain. One is plaques, and the other is tangles. Plaques are large, round, sticky balls of junk. If you looked at a diseased brain in the microscope, you would see gooey balls sandwiched between neurons. Tangles are long, menacing strings inside neurons. They wrap around the cell's nucleus and squeeze it.

So it's like kudzu of the brain?

Right. You've got plaques between neurons and tangles inside neurons. It's the only disease that has these two distinct bio markers. They've spent 100 years trying to figure out which comes first, how they interact and which causes the disease -- or if it's both.

When Mother was moved to an Alzheimer's unit, I found her one day singing songs with a group of people. It knocked me out: She remembered five verses to a song when she could barely sustain a conversation.

I wish I could say having to live through that is unique. That kind of thing is common. Basically, there are two kinds of memories. Long-term memories have the potential to last forever. It turns out that it takes months to form a long-term memory, but once it's there, it's there. The other type is short-term memory. What Alzheimer's does early on is create the inability to form any new memories.

Sometimes the results are almost humorous. My sister gave my mother a beautiful bag of gifts for Christmas. After unwrapping everything, Mother put the gifts back in the bag. Ten minutes later she said, "Oh, look! There's something for me!" She enjoyed herself all over again. And sometimes it brought potential tragedy: She would forget she had taken medication and try to take it again.

There can be pleasantly innocent moments. But, as you say, it is extremely debilitating. From fairly early on, people who are experiencing this have to be watched because they can make fatal mistakes.

When my mother was diagnosed, she was otherwise in good health. She had a sister eight years her senior still alive. We were terrified: "My God, she could live like this for years. What are we going to do?" But the end was very quick, seven months. It got to where she couldn't swallow. One afternoon I sat with her for an hour trying to get her to eat a pear and a small cup of green beans, saying, "Chew, chew, then swallow." It was like turning off lights in the house. One after the other, the systems fail.

If she got all the way to the swallowing problem, she was at the biological end of Alzheimer's disease. At the very end, you can't sit up, move your head. Turning off lights is a perfect metaphor: one by one, in almost perfect reverse order of how the brain is turned on in developing infants. In fact, a doctor in New York came up with a term that is quite eerie -- "retrogenesis" -- which means "back to birth." In the final stages of Alzheimer's, the plaques and tangles have taken care of the thinking part of the brain and are moving into muscle control and beyond, into regulatory functions like breathing.

One day, Mother suddenly said to my sister, "I haven't seen Nanny and Pampa [her parents, who died in 1955 and 1966] for a long time. They are going to be worried because they don't know how to find me." By this time, we'd learned not to correct her. Kathleen said: "You know, I haven't seen them for a long time, either. But they know exactly where you are." And that calmed Mother.

I heard of people who have been in a war and they go back to those experiences. Something you said is very important to emphasize: There is no point in fighting these hallucinations and misperceptions and memories. The only choice you have is to accept that this is their world now and to do your best to make them feel comforted in that world.

Cover photograph by Alexandra Michaels, Image Bank; photo at right by Jim Krantz, Stone

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Great hope for the future

Alzheimer's is an intricate puzzle. Doctors haven't even begun to lay out all of the disease's pieces, or pathology.

Research leads most scientists to conclude that Alzheimer's is due to beta-amyloid, a plaque that builds up on the brain, deadening brain function. A unique wrinkle: Animals don't get the disease, so tests on mice bred to have brain plaque are far from conclusive.

Still, each bit of research brings scientists closer to their goal: preventive therapies and a cure.

Four treatments are on the market today. Called anticholinesterase drugs, they help nerve cells in the brain communicate more efficiently. But these medications treat only symptoms of Alzheimer's -- memory loss, depression -- and provide only moderate benefit to half of those who try them. What's worse, the drugs don't stop the disease's downward progression, even if prescribed early.

Human tests are under way on therapies including anti-inflammatories (such as Advil or Motrin), estrogen, vitamin E and the herb ginkgo biloba. Studies of large populations hint that each of those substances might work: For instance, several studies of women showed a link between early estrogen use and a lower rate of Alzheimer's.

The best hope now lies in two pharmaceutical drugs in human trials. One, a vaccine called AN-1792, was shown in studies of mice to stimulate an immune response against the plaque. The other, a gamma-secretase inhibitor, was shown in mice to block the enzyme that produces the plaque.

Researchers have great hope that results, due in two to three years, will provide invaluable clues to help solve the puzzle.
-- Frappa Stout

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