Losing It

For several years now, Murray Tate has been watching his life--daily rhythms, details regarding his loved ones, directions to the gas station up the street--slip away from him a little at a time.

Alzheimer's is like that.

Murray Tate has vivid memories. Working his way backward through his life, he lets his customary reserve fall away as he describes farming wheat as a boy near the Canadian border outside of tiny Crosby, North Dakota. Nearly six and a half feet tall, he sags his shoulders and holds his 73-year-old arms out in front of him like a man about to be handcuffed. "I used to run a team of four horses in front of a plow until I could barely hold the reins, then go home and do the chores," he says. Murray was the eldest of five children; his alcoholic father left when he was 11 years old. His mother always called him the steady one, the surrogate father who never lost his temper. In high school, while his family was on welfare, he was an A student who lettered in four sports. But Tate himself volunteers none of this information, preferring to sum up his childhood in a simple declaration. "I worked hard--daylight 'til dark."

His most detailed memories are of his 38 years with the Chicago and North Western railroad company. He started there shortly after being discharged from the Army after World War II. The Omaha Railroad, as it was called back then, wasn't hiring, but he had an uncle who knew a superintendent, and on the day he applied they called him in for night duty shoveling coal. The hours were hard and irregular--if you didn't work, you didn't get paid; if the phone rang at 3 in the morning, you got dressed and went. But he tenaciously scaled the union's seniority ladder until he was "number-one man" for the last 15 years of his working life. "Number-one man gets the best jobs," he says, as if this were the last fact on earth.

That meant sitting up in the cab as the engineer on the runs back and forth from Elroy, Wisconsin, just east of Eau Claire. "We'd haul 75, 100 freight cars in one long string," he says. "That's a pretty big job. You've got to know your business."

At one point his wife Lois interrupts the reverie. "Tell him about the last time you were on a train," she says. "Coming home from your sister's in Portland."

The three of us are sitting in the living room in their retirement townhouse in Roseville. "It was two years ago in June," she explains, turning toward me. "We got on the train at 4 o'clock on a Sunday and didn't get home until 8:30 Tuesday morning and during that time he was not with me. He was very confused. Then we get off the train down here at the Amtrak station and he's fine, like nothing happened." She swivels back her husband's way. "Remember? Remember when you thought you were standing on your friend Burt Hendrickson, who had been dead for a year?"

"Well--" Tate begins.

"Remember when you got off the train, wanted to go up and drive it, and the conductor had to put you back on?" To an old railroad man like Murray, this is a greater breach of protocol than standing on his dead friend, and he winces and lets out a curse under his breath. "I remember part of it," he says.

"He was in the upper berth and he kept undoing his straps and finally I thought he was asleep, so I went to the biffy. When I came out, he was trying to get into the sleeper across the hall because he couldn't find his glasses," Lois Tate says.

"I don't know what happened; something got triggered," Murray says. "It was raining, one hell of a rainstorm. I've never seen such a rainstorm."

"You couldn't figure out why you weren't getting wet," Lois says.

"There was a big red ball--about so big--and I felt it was going like this," Murray says, forming his hands around an imaginary object the size of a basketball and then whipping his arms from side to side. "It was shooting at something and I was trying to aim it. It was early in the morning."

But Murray remembers that he was not scared. "It's like the little guys we've got running around the yard here at night. Sometimes they're on the couch over there. And sometimes when I go upstairs, there's this one guy," he adds with an ominous chuckle, "he's about 7 or 8 feet tall, walking with me up the stairs. At the top he stops in front of me. I ducked the first two or three times he showed up. Now I just go through him."

I look hard at Tate to see if he's pulling my leg, a reaction that provokes a quick, nervous laugh. Over on the couch, Lois is sitting with a tight smirk, slowly nodding her head.

"Oh, it doesn't happen all the time," Murray says. "I guess it depends on whether you are tired or not, or what you ate, or some darn thing." He nods toward the picture window. "But there is always something in that yard."

r. William Frey reaches down with both hands into a big white bucket and brings up the brain of a woman in her late 80s who died the day before. He slides it gently into a silver pan. There is only one way to make a definitive diagnosis of Alzheimer's, and that is by examining the brain tissue under a microscope. Because there is currently no cure or effective treatment, this type of examination almost always occurs post-mortem.

Frey is the research director of the HealthPartners Alzheimer's Treatment & Research Center at St. Paul Ramsey Hospital, where he presides over one of the world's largest brain banks. Approximately twice a week, a bucket arrives at Ramsey containing the brain of someone thought to have suffered from Alzheimer's or some other degenerative neurological condition. Frey or one of his assistants then sends about two-thirds of the brain on to the neuropathologist for an official diagnosis, and cuts the rest into 10 cross-sectioned slices that are frozen in liquid nitrogen and stored for further analysis. Something over 1,700 brains have come through the Ramsey clinic. Nearly 1,000 are still in their freezers.

"You need a microscope for an exact diagnosis," says Frey, "but it's clear that this woman had a degenerative brain disease." A normal brain weighs about 1300 grams; this one is barely 900. "A third of the brain is missing from atrophy, from nerve cell loss and degeneration. That caused these invaginations to widen," he says, pointing to the crevices, "and the ventricles to enlarge," he adds, lifting and spreading the lobes to expose a large, cave-like hollow in the lower middle of the mass.

After a little cutting he locates the hippocampus, an apparatus about the length and width of a large worm. Tucked inside the temporal lobes, it runs from the front to the back of the brain and functions as sort of a central memory switching terminus. The hippocampus is critical to short-term memory, and it is almost always damaged in Alzheimer's patients.

Frey's cross-sections reveal that the brain's grayish surface does not extend throughout the tissue; visually at least, it's more like a thick rind surrounding predominantly white brain matter. Generally speaking, this outer gray matter functions as storage space, while the white matter is more involved with the transmission and movement of information. Damage to the white matter is common in diseases such as multiple sclerosis; Alzheimer's mostly attacks the gray matter.

But this is all very general, Frey warns me near the end of our talk. "It's important to remember that the brain is very complex, and different functions are using parts from all over, so it is a little hard to get too specific. Frankly, we don't know much about what some areas do. We're in the dark a lot of the time," he says.

"We know a lot about what happens to the brain [in Alzheimer's cases]," concurs Dr. David Knopman, director of the University of Minnesota's Alzheimer's clinic. "But we don't know why it starts to happen."

What happens is that the brain cells in Alzheimer's patients begin to degenerate and die, particularly in the areas involved with memory and cognition. More specifically, nerve cells in the brain fail to produce enough of a substance called acetylcholine, which is the chemical messenger primarily responsible for transmitting memory information from one cell to the next. This deterioration is accompanied by an accumulation of abnormal proteins that further disrupt brain functions. One of these abnormal proteins, amyloid, causes degenerative nerve cells to harden and form plaque; another protein, tau, is found in dying cells that are twisted into fibrous tangles. These plaques and tangles are what the German psychiatrist Alois Alzheimer saw under a microscope in 1906, providing a medical explanation for the progressive dementia from which a certain segment of the population--mostly elderly--had always suffered. Today microscopic plaques and tangles are still the definitive physical basis for an Alzheimer's diagnosis.

After Alzheimer's discovery, there were no major research breakthroughs until 1976, when the acetylcholine deficiency in the brain cells of Alzheimer's patients was confirmed. Initially, this was thought to be a momentous breakthrough, akin to the discovery that patients with Parkinson's disease had a dopamine shortage in their brain cells. But whereas Parkinson's patients improved markedly when given dopamine-replenishing drugs, acetylcholine treatments proved far less effective for Alzheimer's patients. The reason, apparently, is that the degeneration of brain cells in Alzheimer's patients is a more complex and systemic process: While the brain cells that produce acetylcholine appear to be affected first and most severely, other types of cells and other chemical transmitters are breaking down as well.

The most significant aspect of Alzheimer's research in recent years involves the likelihood of a genetic element at the roots of the disease. Experts in the field now generally concede that there are people whose genetic makeup puts them at a much higher risk of developing the disease, and tests to determine the presence of "Alzheimer's genes" have recently been made commercially available. Many experts question the value of the tests, however, because they are not definitive and because the disease, in any case, remains incurable.

The genetic connection may be pointing a way toward new treatments that effectively reduce the number of Alzheimer's cases. Studies using sophisticated brain imaging techniques have shown that people who are genetically at risk for Alzheimer's but not yet manifesting symptoms tend to have reduced glucose metabolism in much the same way that Alzheimer's victims do. This would seem to indicate that the disease starts attacking the brain a long time--maybe even decades--before any symptoms are apparent. Because those symptoms become noticeable relatively late in life, it follows that any means of delaying their onset would reduce the eventual number of Alzheimer's cases. According to one Duke University researcher, a five-year delay in the onset of symptoms would reduce the number of Alzheimer's patients by half.

For that reason, part of the $310 million in federal funding devoted to Alzheimer's research now goes toward developing drugs and treatments to retard the progress of the disease. There is currently one drug on the market, Cognex, designed to prevent the breakdown of the acetylcholine chemical, but it appears to be effective in only about 20 percent of Alzheimer's cases, most of them early-stage.

In addition to a number of new drugs currently being tested, there may be some over-the-counter preventative measures available. For reasons no researcher fully understands, anti-inflammatory drugs have been effective in reducing Alzheimer's symptoms; the incidence of the disease is very low in people with arthritis who take a large amount of painkillers such as ibuprofen. And Frey notes that Vitamin E may help protect the health of the brain's receptor cells. Meanwhile the demand for improved Alzheimer's drugs and treatments is obviously huge. An estimated 4 million people in this country now have the disease, and the steady aging of the population has that number climbing rapidly.

Because Alzheimer's involves such complex, diffuse brain processes, it is a disease of infinite variation. "Alzheimer's is like a different disease in each person," says Nina Grafenstein, the Alzheimer's program director at the Lake Ridge Health Care Center in Roseville. "Each one is as individual as a snowflake."

urray Tate was diagnosed with Alzheimer's shortly before Christmas in 1993. His symptoms came on so gradually they were easy to overlook. There were little incidents, sure--like the time in 1989 when Lois started canning tomatoes while Murray set up the home entertainment system they had just bought. About four hours later, her work finished, she found her husband sitting cross-legged on the floor and staring helplessly at the pieces. Another time Murray, who had always liked working on cars, poured windshield wiper fluid in with the crankcase oil.

Then one day he got hopelessly lost buying gas, just a mile or so up the street. "I spent about two hours trying to come home," he says ruefully. "The streets seemed to be going a certain way and I was going along and I knew I was right but I was wrong. I knew I was right but then I knew I was wrong, everything else said I was wrong." He chuckles. "I had a hell of a time. I knew the house was what I was looking for. I finally stopped in at a service station and got directions and I still got lost. He told me to just go down this road and take a right. And I went down the road and I knew I was right. But I was wrong again."

He and Lois went to see Dr. Richard Nadler, a geriatrician and internist who had been their physician for about three years. He asked Tate some basic questions: What is the year, date, day of the week? Nadler offered three words--Cadillac, rose, ball--and asked Tate to repeat them, first immediately and then after three minutes. Nadler then told him to focus on the number 100 and subtract by sevens: "an exercise where you have to remember the instructions and then remember how to carry them out," Nadler explains. Overall, the doctor saw that "there were some important things that drifted by Murray."

"When the doctor asked him what year it was," Lois confides, "Murray would say 1934."

Some tests were run to rule out other possible causes for the memory lapses, like low thyroid production or a minor stroke. Two heart attacks had forced Tate to retire from the railroad 15 years earlier, and while Alzheimer's is the diagnosed cause of more than 60 percent of the dementia symptoms experienced by people over 65, the second-most prevalent diagnosis, encompassing nearly 20 percent, is a mini-stroke, or "multi-infarct dementia," common to people with heart problems. There was also a period in his life when Murray Tate drank heavily, which could have had an impact on his brain activity. Another possibility was that he had a relatively rare brain disorder called Lewy Body Disease, which is characterized by hallucinations and delusions even at a fairly early stage.

"Even when you do a brain biopsy," says Nadler, "the diagnosis is not 100 percent. It might be possible [that Murray has Lewy Body], or he might have Alzheimer's. There are a number of problems that can give you dementia of the sort he has. Unfortunately there are very few that you can do anything about."

When Nadler told Tate that it was likely he had an incurable, degenerative brain disease, he remembers Murray saying, "'Oh yeah, I can see that.' He was very matter-of-fact, as if now he had an answer to an important question. He had to take it home and process it."

After learning the diagnosis, the Tates enrolled in the Family Workshop, a now-defunct seven-week program designed to give families exposure to practical information and get them working together to better cope with the demands of the disease. Dr. Wayne Caron, a family therapist who worked in the program in conjunction with a gerontologist and an occupational therapist, says he assumed incoming families had already gone through a long ordeal before the diagnosis. "The symptoms of Alzheimer's can be slowly emerging for years. All that time, a person is struggling with the feeling that something is wrong with me but I don't know what it is. The family feels it too."

According to members of the family, Murray was always stoic. "He's a classic Norwegian," Lois says. "Y'know, the one who loved his wife so much he almost told her." More privately, Lois and at least three of the four children in the family believe Murray's repressed emotions stem from his traumatic childhood, including physical abuse, and the responsibility he bore at such an early age. "The way our dad used to show us he loved us was to fill our cars with gas and give us a $20 bill," says Joellen, the second-oldest child. Her favorite memories are of playing out in the garage while Murray tinkered on the junk cars he'd buy for $50 and sell for a modest profit once he'd gotten them running. Any conversation between them consisted of small talk; occasionally she'd hear Murray whistle or sing to himself, happy to be caught up in the task at hand.

But about a year or two before his Alzheimer's diagnosis, Joellen saw a marked change in her father's emotional makeup during her biennial visits from her home in Alaska. "About four years ago, there was a point where any time you left he would break into hysterical sobs," she recalls. "I think it was because he thought it was the last time he would be alive to see me. The first time it happened, that might have been the first time I saw my father cry."

The other children have similar memories. "He'd get emotionally charged up and just hang on to it," says Ross, the only son. "He'd be quiet, just sit there watching TV with tears in his eyes. I'd ask him about it and get a minimal response; he'd turn the other way or go off to another room." Maureen, the youngest daughter, says, "I think he was worrying about what was happening to him, and he was hanging on as hard as he could until his grandson and granddaughter were born. I think that was important for him. In his own way, I think he has been more emotional. He has told my mother he loved her. And I've probably seen him cry more times in the last five years than in my entire life."

Nevertheless, Caron concedes he found Murray "remarkably sanguine after learning of something that would have horrified most people." He attributes this in part to Murray's stoicism, in part to his previous near-brushes with death ("they've already cracked his chest open"), and to the support of his family, noting that the people who experience the most difficulty are the ones who are alone.

Dr. Knopman, the neurologist, favors a more medical explanation for Murray's "sanguine" reaction to his condition. "Only rarely do people get distraught," he says. "Part of the reason it doesn't happen more often is that one of the fundamental aspects of the disease is to impair insight. The patient is less likely to understand the implications for his future."

t is difficult to know exactly where Murray Tate stands on the continuum of Alzheimer's deterioration. Life expectancy generally ranges from five to 15 years once the symptoms have become apparent, which, if you date the condition from the home entertainment center episode, puts him at six or seven years. His panic attacks have mostly subsided and his children say he seems more at peace with himself.

"Sometimes I'll start downstairs without thinking and sort of wake up and wonder, 'What the hell am I doing over here?'" he says. "Sometimes I'll be doing a little job and need the pliers or a screwdriver or some damn thing. But I'll go get it and forget what I'm doing. I have to sit down for two or three minutes until it comes back to me. But I don't worry about it. It's amazing how little the little stuff bothers you if you just let it go."

While he is holding forth in great detail at the kitchen table about the Army and the railroad, the phone rings. It's a representative of the cemetery where Lois's parents are buried, calling to get some information. He is able to supply the first and last names of his late in-laws and tell the caller that he and his wife have moved to a new condo in the past two years. But when he is asked to supply his new address, he draws a blank until he remembers that it's printed on the wristband that he wears in case he gets lost.

"Last weekend our old neighborhood group got together; it happens about four times a year," he says. "We all built on the same block years ago and we sit around and B.S. about what happened in the '50s and all that stuff. I'll be sitting there and I'll go to say something I'm thinking about and then I can't. It don't really want to come out. They don't even know it. I don't talk a hell of a lot anyhow. They are all talkers and I just sit there and be quiet--look at this guy, look at that guy, and pretty soon things get cleared up again. Well, not exactly cleared up but--"

So you'll be listening to people but you won't really know who they are for a while?

"Yeah, that's right."

So you have to be patient?

"Oh yeah. And if you have been in that situation before, it makes it that much easier."

It weighs more heavily on Lois, but she's used to bearing a lot. She raised their four children while Murray worked his crazy hours for the railroad--"When he was home he wasn't so much like a dad as an uncle that came to visit," she says--and through the years they both came to value their independence. As Murray has lost his to the disease, it's obviously been hard. Even Lois admits she has always verbally dominated Murray. Now his Alzheimer's disease has given them each a trump card: She can always dispute his version of events; he can always say he doesn't remember what she told him.

"Sometimes my dad will walk into the living room and say, 'Which way is up?' then turn around and wink at me," says Joellen. "He's pretty sharp and lucid sometimes, and during those times I think he says to himself, 'I'm going to give her hell.'" But Joellen also remembers a time about a year and a half ago when her father got lost in a shopping center. When she found him, he was crying and panic-stricken. The first words out of his mouth were, "Where's your mother?"

"He'll come in," Lois says, "and I'll ask if he's shut the garage door. He tells me that he did, and then a neighbor comes by at 10:30 at night to say that our garage door is open. He went to bed the other night and left six lights and the television on. The other day after I'd told him to put on some deodorant, he came back and there were two big white spots underneath his arms--on the shirt.

"I do a lot of praying for patience, but so many times God says no. Because I holler a lot; sometimes I really let loose. And he ignores me," she says, breaking into a hearty laugh. "And that isn't brand-new either.

"He hardly laughs anymore. Sometimes I can get kind of a grin out of him; mostly it's just nervous chuckles. When it was just the two of us before he didn't laugh much, but I knew how to trigger it. We liked to dance. He's forgotten how. We went to a wedding last June and he didn't know where to put his feet. We used to mostly polka--now that's gone. Music is often the last thing Alzheimer's people lose," she says.

To alleviate some of her burden, Murray goes to daycare three or four times a week at Lake Ridge Health Care Center just a mile down the road, where he often has breakfast and lunch and reads the morning paper. "They'll latch on and keep a conversation going if you say something," he observes with a note of appreciation in his voice; when the weather is nice, he sits out on the sundeck with three or four other regulars and tries to rustle up a card game. Murray has played cribbage since the days on the farm when there was no electricity and the nearest neighbors were 15 miles away. Nowadays he lasts no more than a game or two before his concentration fades.

For her part, Lois attends a weekly support group of Alzheimer's caregivers. "A gal in that group asked me, 'What are you going to do when he gets violent?' And I said, 'Pray that his heart takes him first.' I guess many of them go violent or go comatose. When he stops knowing me it will be difficult. Right now he just doesn't know my birthday. But then he never has. We can't afford a private hospital. If and when the time comes, I hope to get him into the VA."

any medical professionals believe that the dominant memories in Alzheimer's patients are often the ones that confer a sense of identity. Most of all, Murray Tate remembers the railroad. When Lois brings out pictures of Murray at a reunion with his railroad buddies last year, there is a uncharacteristically broad smile on his face. "Murray was one of the best," says Al Fohrman, a retired brakeman who worked alongside him for better than two decades. "He could sense when things weren't quite right, when you needed to pick up the pace a little bit or get something straightened out. Very few people I ever worked with had such a feel for the job. We worked long, tough hours together--probably spent more time together than we did with our wives."

When his mind starts to wear thin, Tate usually goes back to the railroad. Nearly an hour into one of our conversations, I ask him if the disease ever scares him. "No reason to be scared," he says. "I never paid any attention to it. Because when you are working on the railroad, you don't keep up with anything else. It's a one-shot job, more or less."

"Is it hard to remember what I'm saying?" I ask.

"Sure it is. You've got three or four diesel engines. You're pulling 200 cars, keeping them in line all over the track."

Occasionally when he's lost, something will shock him back to the present. When I ask whether he has any grandchildren, he says, "No." No grandchildren? I repeat. "Wait a minute. What am I talking about? My boy has got a son and my daughter has got a girl. A lot of that stuff, you just get a glimpse of it and then you don't see it anymore. And I don't know what causes that. I don't know." It is the first and only time I see him angry.

But the mood abruptly lifts. "Sometimes I think I am just as sharp as I was a few years back. Because I used to--hell, when I was a kid and I wanted to go to college, I wanted to be a civil engineer. Couldn't do it now, because, well, just like when I try to write, I can get out about one word, maybe two words. Then it gets worse and worse."

Because of the Alzheimer's?

"Yeah. You have to be tougher than it is. If the doctors can't handle it in 10 years, I'll get rid of it. I won't let it get me off. We'll go in and cut the old germs out, or whatever it is they've got. When they started this prednisone study, that's why I did it," he says, referring to a clinical study of anti-inflammatory medications in which he's enrolled. "I only have a few minutes to go; why tie up some young guy for a few months, or years? Give it to an old guy and see what happens. And if they found out what is causing this Alzheimer's in the head, or if they don't find out, all they've lost is just what little of the life I've got left. Or whoever is studying it, I've been through enough of this. I've lived a lifetime, maybe two or three or four or five. I have no regrets." CP

Mary Ellen Egan and Rebecca Harrison contributed to research for this story.

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