Alzheimer's In The Family

By MICHAEL D. LEMONICK

Anne Nagel seems determined to greet every last one of her guests personally. "I'm so happy to see you! I'm so glad you could make it," she says, flashing her infectious smile over and over. Some five dozen family members--brothers, sisters, children, nieces, nephews, grandchildren--have crowded into Maguire's, an old-fashioned wood-paneled Irish bar and restaurant in the Bayside section of Queens, N.Y., festooned on this chilly, bright November Saturday with pink and purple balloons for her 90th-birthday party.

To an outsider, Anne appears perfectly normal. She is impeccably dressed, her white hair is immaculate, and she wears a corsage of pink baby roses on her lapel. She engages in conversation, cracks jokes and seems thrilled to be surrounded by so many loved ones. But talk to her daughter Barbara Reiter, and it's clear that Anne isn't normal at all. She insists that she didn't know about the party, even though, Barbara says, "I told her about it every day for at least a week." Barbara got her mother dressed that morning and took her to the beauty parlor as well. "I could have taken her Friday," says Barbara, "but she has a tendency to put Vaseline in her hair."

Anne Nagel, ne Weiss, is almost certainly in the early stages of Alzheimer's disease ("almost," because a definitive diagnosis can be made only after death). The disease probably also afflicts her sister Helen, 88, and her brother David, 94. Her brother Nathan and sister Sylvia, both now dead, also had Alzheimer's. That's half the 10 Weiss siblings suffering the memory loss and cognitive impairment of this terrifying disease.

Why are the Weisses so vulnerable to Alzheimer's? One reason is that they tend to live long lives; advanced age is a major risk factor for late-onset Alzheimer's. But scientists are convinced that defective genes are also involved. Four have already been located--one known as ApoE has been linked to late-onset Alzheimer's--and last week several new mutations on a gene associated with the much rarer early-onset Alzheimer's were tentatively identified, but it's clear that there are more genes to be found. That's why the National Institute on Aging (NIA) began last fall to recruit families with multiple Alzheimer's victims, scanning their DNA to see how the genes of the healthy differ from those of the sick.

The Weisses are one such family, which is why Brenda Goldfine, 64, Helen's daughter and Anne's niece, was in Dr. Richard Mayeux's office two weeks ago. The Columbia University neurologist, executive coordinator of the NIA's Alzheimer's Disease Genetics Initiative, quizzed her about her family history. Then he asked whether she had noticed any problems with memory. "I'm not the girl I used to be, that's for certain," she said. "It isn't terrible, but I think I make more mistakes than I used to." She got the day and month wrong when Mayeux asked, but she passed the rest of the cognition and memory tests "with flying colors," he says. "She did spectacularly well."

Compassionate as Mayeux is, this is a scientific exercise for him. For Brenda, it's her life. While most people in middle age have a vague fear of joining the 3.5 million Americans who have Alzheimer's, the Weisses know their genes put them at the head of the line. Watching her mother's mind slip away bit by bit--Helen can barely talk and has trouble remembering how to use a toilet--Brenda may well be getting a chilling glimpse into her own future. But she is impressively sanguine about her fate. "It hasn't changed the way I live," she says. "It's not on the forefront of my brain. I don't know if I'll have Alzheimer's or if I won't, but worrying isn't going to help."

That doesn't keep her cousin Barbara Reiter, 56, daughter of the birthday girl, from worrying anyway. Like Brenda, she's philosophical. "How do I feel about it?" she asks. "If one thing doesn't get you, something else will." But she's also scared. "Anybody who has experienced their parents getting older and losing them is at some point going to experience the fear of 'What's going to happen to me?'"

Barbara and her cousins make a lot of jokes about Alzheimer's and "senior moments." But, she says, "I think that's just a knee-jerk reaction to being frightened. It's covering up the sadness." If scientists find the gene or genes responsible for her family's affliction and devise a test--something that could come out of Mayeux's research--she won't be in a rush to take it. "Some people can go in and get tested for the gene for breast cancer," she says. But while there are treatments for breast cancer, there aren't yet any for Alzheimer's. As long as that's the case, she says, "I don't really want to know."

Barbara's son Matt, 26, who lives with his grandmother Anne four days a week, also isn't interested in knowing. "If somebody came up tomorrow and said, 'This is the cause of Alzheimer's,' I'm obviously going to do whatever I can to try to avoid it," he says. "If Alzheimer's was being caused by food additives, I'd stop eating those. But if things are going to happen to my brain, there's not much I can really do about it."

So far, Mayeux's work with the Weisses and the other 250-odd families participating in the study hasn't yielded any new Alzheimer's genes, but, he says, "the feeling is that we're very close." Over the next three years, he hopes to recruit 1,000 Alzheimer's-afflicted families, which should considerably boost the chances of success. "The hope," says Mayeux, "is that someday patients have a genetic profile done, just like they have their cholesterol done, and we'll say, 'Look, this is what's wrong. And you've got to take this medication. Otherwise you're going to develop Alzheimer's over the next few years.'"

But for now the Weisses can only feel some satisfaction from helping medical science and hope that they will somehow beat the odds. And as they made clear at Anne's 90th-birthday party, where everyone ate and drank and laughed their fill, they will do their best to enjoy life as it comes. --Reported by Sora Song/Bayside

With reporting by Sora Song/Bayside