Twenty-Four
THE LUCKY ONES
DOUG’S MOVE INTO the Tioga nursing home marked another grim milestone in Karla’s life. Coupled with Dean’s decision to return to the oil fields, and following closely on the heels of Brian’s death, she was reminded more than ever that she would soon be the only sibling left, and she was cracking under the strain.
Compounding her stress levels was the fact that she was now working two jobs. By day, she worked as an administrative assistant at a college; by night, she moonlit at a service that typed legal paperwork. There were days when she worked from 8:00 a.m. to 10:00 p.m. Like Gail, she developed tremors in her hands, and when she was home, she cried; sometimes, she even had to leave work early to regroup.
It helped to talk to Gail, which she did constantly—not just about the disease, but about any little details that came up in the course of her daily life. And Gail unburdened herself, too, both of them recognizing that they shared an understanding of how hard it was to survive the death of people they both loved.
“We’d dump all our problems and then say, ‘Well . . . have a nice day,’ ” Karla said.
Karla was turning fifty, but she had realized a fundamental truth: All your life, you will find a time when you simply need your mother.
• • •
In the summer of 2008, twenty-three-year-old Chelsey McIntyre, Steve and Lori’s youngest, was facing the toughest dilemma of her life. She was a student at the University of Wyoming and had just discovered she was pregnant.
She had been dating a fellow student, Jeremy Francom, who had graduated and planned to move to an Indian reservation to become a teacher. The relationship was fizzling out when, about a week before Jeremy was scheduled to move, Chelsey found out she was expecting.
“It was very hard,” she recalled. “It took a long time for me to come to terms with it.”
Not knowing where else to turn, she called the one person who always seemed to know what to say: her grandma Gail. Predictably, Gail—lover of all children, especially babies—was thrilled at the news. Her enthusiasm bolstered Chelsey’s courage, and finally, the prodigal daughter called Lori.
“She was upset at first, and then I think it finally set in: We’re going to actually have a grandbaby. That’s what she wanted,” Chelsey said. Lori’s wish was coming true; she would know at least one grandchild before Alzheimer’s took away her ability to connect.
Chelsey’s bigger concern, she confessed to her mother, was telling Steve. He was adamant that she finish college, and she just couldn’t bring herself to tell him about this complication. So Lori broke the news. For weeks, there was nothing but silence from Idaho, where Steve and Lori were now living.
“I’ve had time to think about this,” he said, when he finally called Chelsey. “I wanted to process it before I said something I didn’t mean. I just really needed to think about it.”
And then he told her: “I really think this happened for a reason.”
• • •
Though Jeremy was committed to raising his daughter, Chelsey didn’t think they should marry just because they had a child. They remained on friendly terms and stayed involved with each other’s extended family, and they worked hard to coordinate their parenting styles, even when he moved three hours away to begin his teaching career.
Claire Kennedy Francom was born in March 2009. As she grew, she and her cowboy boots were inseparable. She divided her time between her mother’s home and her father’s, despite the distance. When she was with Jeremy, she loved to Skype with her mother; when she visited Steve and Lori, she bossed her grandmother around, as though they were the same age. Emotionally, because of the disease, they often were.
With Claire’s arrival, Chelsey began to question whether she wanted to learn her own genetic status. Knowing she could have passed the mutation along to Claire, she decided to wait. Her own mother’s diagnosis had been devastating, and she was already worried. Adding to the burden of young motherhood seemed like a bad idea, and both her parents were adamantly opposed to any of their daughters finding out their status, fearing the knowledge would burden them unnecessarily in their young adulthood.
“It’s hard to make that decision,” Chelsey said. “Do you have kids no matter what? You need to live your life as normal as possible. Or do you think about the next generation?”
The notion of parenthood was encroaching more each day on Chelsey’s cousins. Following seven years of college, Dean’s daughter Lindsey graduated with a doctoral degree in physical therapy. After some initial hesitation, she enrolled in the DIAN study at the University of Pittsburgh. She waited until she was sure that she did not have to learn her genetic status to participate.
“For right now, I’m perfectly content not knowing,” she said. “If different treatment options become available, I might reconsider. But it’s still at the point where finding out does not benefit me in any way, and it’s not worth the emotional distress.”
She became engaged to her boyfriend, Jon Sarkilahti, and together they bought a house in Minnesota. She knew she wanted to have a family, and she worried about how the mutation might affect those plans.
“Should I even have any kids? I struggled with that for a very long time,” she said. “Knowing that the gene is in the family, would that be wrong of me, bringing a kid into this world, knowing that they had a fifty-fifty chance of having it? Or even if they don’t have it, watching me struggle with it if I do have it?”
The question of children continued to dog the DeMoes: Did they have a moral obligation to discover their status? Hearing the scenario, bystanders often assumed the answer was obvious: Yes, anyone capable of childbearing, or of fathering children, should find out. If they tested positive, they should not have children.
But the day-to-day reality for someone who actually lives that situation is far less black-and-white. Deb DeMoe, who turned so often to her faith for answers, consulted her pastor. He pointed out that any number of circumstances or illnesses could take children from their parents: Accidents. Cancer. Meningitis. Watch therefore: for ye know not what hour your Lord doth come. The only difference in the DeMoes’ case was the fact that they had some warning.
Though Lindsey decided against knowing, it was important to her that she contribute to a treatment, even if she never needed it herself.
“After Brian passed away, I wanted his life, and my grandpa’s life, and all the other family members that had gone through the disease to be worth something, and to be able to leave a better legacy than how they passed away,” she said.
• • •
A few months after Brian’s death, Karla’s daughter, Amber Hornstein, was married in an elegant church wedding in Fargo, attended by three of the family’s littlest members—Savannah, Claire, and Kassie’s daughter, Brianna—as flower girls. The entire extended family gathered to celebrate, including the cousins from Oklahoma and Wisconsin, and Gail was thrilled.
Slender, blonde, and blue-eyed, Amber made a stunning bride. She was working as a physician’s assistant when she married, and a year later, she would enter medical school. She had been in high school when her uncles and aunt started getting diagnosed.
“It was the second or third [diagnosis] when I started to pick up that wow, this was serious,” she recalled.
Like the rest of her family, Amber was worried about her mother.
“There are times when I think she would rather have the diagnosis,” and spare one of her siblings, Amber said.
Her father, Matt, did not doubt that this was true.
“She’s always thinking about it, always talking about it,” Matt said. He summarized Karla’s philosophy this way: “This is my fate. This is my job. This is my responsibility now, to take care of my family.”
Karla was always at her happiest when she was surrounded by twenty relatives in a single room. “She’s never going to lighten her load, until the day she dies,” said her son, Cole. “She will never stop.”
For a time, her
daughter Amber had toyed with the idea of working for Bill Klunk, shadowing him.
“I live it every day,” she said of the disease. “More than anything, I would love to find a cure.”
Though she gave up the idea of working in Pittsburgh, she did put her medical training to use within the family, checking up on everyone’s prescriptions and helping them interpret information. She believed her experiences would help to shape her into a better doctor.
One night at Grandma Gail’s house in Tioga, Amber was sitting up talking with her cousin Chelsey McIntyre, who broke down crying and confessed something she hated to admit: She resented Amber and Cole for being free of the disease, for never having to watch their mother lose her mind, for never having to worry about passing the mutation on to their own children.
“I was shocked—so shocked,” Amber said. “I know I’m lucky.”
But thoughtfully, she added: “I guess I didn’t realize how lucky I was until that moment.”
And though some of her cousins had already been cleared, in the back of Amber’s mind, a terrifying thought smoldered: “We’re having all these no’s, but I feel like a yes is coming on,” she said. “It makes me physically ill to think about it.”
• • •
After the champagne toasts were given at Amber’s wedding and the dancing was done, after the plates were cleared away, the extended family gathered at Karla and Matt’s house, including Sharon and both her daughters, Sherry and Sheryl, who had made the trip from Oklahoma. It was then that Karla realized Sharon’s older daughter, Sherry, had the disease. Amber’s premonition had been correct.
In between working, planning the wedding, and handling the aftermath of Brian’s death, Karla had compiled a series of family photos into a slide show that she titled “Too Early, Too Many.” It brought back the memories that had formed the mosaic of their lives: Moe holding Brian, as a baby, in his own mother’s house; the DeMoe siblings, first as clean-cut, Brady Bunch–era youngsters, later as shaggy-haired teens; cousins and babies, aunts and uncles. Here were Dawn, Colleen, and Robin Miller as little girls in dresses Pat had sewn. There were Jerry and Sharon, standing together and smiling, and later, Sharon, smiling bravely as her husband lay in frail repose beside her.
The family sat, transfixed by the scenes from their life; many began weeping. The juxtaposition of the occasions, this one so close to the joy of the wedding, reminded them of the obligation that fate had assigned to them: Tragedy would intertwine with their blessings until they found the thread that would lead them out of the labyrinth.
Twenty-Five
FOLLOW THE SCIENCE
IN 2011, WHILE the DeMoe family regrouped at Amber’s wedding, about fifty of the Colombian paisa were traveling in groups to the Banner Institute in Phoenix for brain scans that marked the beginning of what Lopera had long sought for his families: a sliver of hope. Eleven of the paisa already had symptoms; nineteen had no symptoms but carried the mutation that would guarantee the disease; and twenty were noncarriers. They were anywhere from twenty to fifty-six years old, and for many of them, the trip to Phoenix was the first time they had ever traveled outside of their immediate home turf or sat on an airplane.
Tariot and Reiman welcomed the group, most of whom they’d met previously on their trips to Colombia. They asked their guests: What would make this trip more comfortable for you?
The answer was unanimous. The Colombian kindred, to whom family was paramount, wanted to visit the doctors’ homes. They wanted to see how these men lived, eat the food they ate, meet the people who were important in their lives. If they were truly going to trust these men to lead them out of this ancestral curse, they wanted to know whose hands they were grasping. And so it came to be that Pierre Tariot and his wife, Laura, welcomed groups of the paisa to their gracious, Southwestern-style home. They shared food and drinks, mingled, visited.
“We remembered what you told us, so welcome to our home. My house is your house,” Tariot said. “You asked what’s important to us, and you’ve asked why on earth we have your pictures on our walls at work.”
The family members looked at him expectantly.
It was to remind him, every day, what his work was for, he told them. When he was discouraged, he wanted to see why he could not give up. And when he scored small victories, he wanted to see who would benefit.
Afterward, they sat around the dining table, a group of people who had never met one another but were distantly related and genetically linked by the mutation in their bloodline. It was their second day in Phoenix, and the experience was sobering, bonding; the potential history of the moment loomed large in the atmosphere.
“This is so hard,” someone said at last. “Half the people at this table are going to die from Alzheimer’s disease.”
Thinking about it a year later, answering the question he had been asked countless times, Tariot said: “So why are we inspired? How could you not be?”
• • •
Obtaining visas for natives of Colombia—a country the US State Department eyes with suspicion—was just one of the myriad complications facing the Banner team as they prepared for drug trials. For starters, they needed to find a drug, and it had to be the right one. The paisa had been waiting generations for the medical field to advance to the point where it might start offering answers instead of asking questions; the doctors were mindful of that burden and of the narrow window of opportunity that had opened to them. But they also had to run trial participants through a battery of tests to determine their baseline status on key biomarkers. In short, the doctors wanted to observe the amount of amyloid they had in their brains, if any, as well as other indicators of how the body was manifesting the disease. These results would serve as a basis of comparison later, after the paisa received the drug injections, to determine whether the medication had had any effect.
While the research team searched for the right drug to test, the paisa came to Phoenix to get their baseline PET scan readings. It was critical for the team to know when amyloid began depositing in the brain, so they could identify the youngest possible age for inclusion in the trial.
What they found shocked them.
Doctors normally describe the early stages of Alzheimer’s as mild cognitive impairment. If you start to forget appointments or can’t remember the steps involved in completing a task, mild cognitive impairment (or MCI, for short) is likely the term that will appear in your medical records. In people who carry the mutation, this description might apply in their midforties, a startlingly young age. But what the Colombians’ brain scans revealed was proof of what people like Paul Aisen had been saying: that even a decade before that, long before a person’s behavior is at all affected, the brain is changing in ways too subtle to appear to the outside world.
In the paisa, amyloid began increasing at the age of twenty-eight and appeared to plateau at the age of thirty-six, but mild cognitive impairment wasn’t noticeable until an average age of forty-five. A diagnosis of dementia happened at around fifty-one. This is consistent with the idea that the tau cascade happens after the amyloid plateaus and is associated with the worsening symptoms.
Since the subjects were all from the same family, and lived in the same part of the world, the number of biological and environmental variables was much smaller than, say, with the DIAN test subjects, who came from all over the world and could have been affected by any of the three known mutations.
“This is a special population,” Reiman said of the paisa. “The power we have to see things with this one mutation, it’s amazing.”
What’s more, he saw similar changes occurring in the brains of people with the more common ApoE4 genetic risk for Alzheimer’s, the type that both the Banner group and Aisen and Sperling were studying. The brain of a thirty-year-old ApoE4 carrier, for example, wasn’t metabolizing glucose as quickly. Some middle-aged people experienced brain shrinkage. And the higher the genetic risk for Alzheimer’s among people in their early sixties, the more amyloid the
re was in their brains. Those results convinced Reiman that the disease was similar enough in both populations that anything that succeeded with mutation carriers would also benefit people who suffered from the more common form of the disease. They appeared to be on the right track.
As the Colombians rotated into Phoenix for their baseline scans, Tariot and Reiman invited fellow Alzheimer’s researchers from around the country—who were not directly involved in their efforts—to attend meetings so they could outline their idea for a drug trial. There, they made their pitch: If preventing amyloid accumulation before the tau cascade began would halt Alzheimer’s, this was their chance to prove it.
To spread out the risk pool—so the paisa would not become the sole guinea pigs for an American pharmaceutical company—the study would include a handful of Americans under the auspices of the FDA; in Colombia, that country’s equivalent—Instituto Nacional de Vigilancia de Medicamentos y Alimentos, or INVIMA—would regulate participation.
As is often the case with scientists, the researchers’ meeting hosted by Banner yielded no complete consensus; some said the Banner team was onto something important, some said they were setting themselves up for an impossible task. On the final day, each person in the room briefly summarized his or her opinion. The last doctor to speak was Francisco Lopera. His closing words were: “Remember that our families are waiting for you.”
• • •
While members of the Banner team looked for an anti-amyloid drug to test on the Colombians, they had to court the pharmaceutical companies carefully and ask unexpected questions. If the companies had ulterior motives, they wanted to suss those out.
One of those questions was: Why are you willing to put this asset at risk? The very idea of spending millions to create a pharmaceutical and offer it to a wholly unique population was riddled with business risk factors that many companies would consider unacceptable. The drug could unveil complications unique to the paisa or the PS1 mutation that might doom its prospects for the general population; it could prove to be unsafe; there were no guarantees the FDA would approve it. If they did, competitors looking at the study’s results could potentially use the information to reverse-engineer the drug and steal it. And to date, not a single Alzheimer’s drug had succeeded in budging the disease.
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