The Inheritance

by Niki Kapsambelis

  Scans had illustrated brain changes in mutation carriers decades before their symptoms appeared, convincing Reiman that treatment had to begin even earlier than many in the field thought—before the age of twenty-eight. At a minimum, the Colombia trial—which targeted only amyloid, since tau prevention treatments were not yet available for human trials—should be the definitive test of the amyloid theory, saying once and for all who had it right: the Baptists or the tauists.

  But clinical trials are expensive, and medical research is a results-driven field.

  “By the way, the field’s not going to give us that many more shots on goal,” Reiman said. Drug companies, feeling pressure from their investors, would not keep sinking money into expensive failures. And many researchers depended on such funding to do their work, and on successful research to keep their jobs. “So we’d better get it right.”

  Twenty

  EVERYONE SEES THE POWER

  WHEN BILL KLUNK was a graduate student at the Washington University School of Medicine in St. Louis, he first crossed paths with John Morris, who was completing a postdoctoral fellowship. Because both men were interested in the science of brain disorders, and specifically Alzheimer’s disease, they continued to communicate as professional colleagues. Thirty years later, that relationship would lead the DeMoe family to their first real shot at a meaningful treatment.

  Like Reiman and Tariot, Morris believed that Alzheimer’s formed much earlier than anyone had ever suspected, and that identifying the right time to administer a drug was the key to preventing—or at least delaying—the disease.

  In 2008, in an effort that paralleled what was happening at Banner, Morris began taking his first steps toward early prevention. From Washington University, where he was now a professor of neurology and head of its Alzheimer’s Disease Research Center, he launched an international study of people who carried the known Alzheimer’s mutations. Klunk, who headed the sister center at the University of Pittsburgh, contributed his patients—with their permission—to Morris’s larger effort.

  Morris called his study the Dominantly Inherited Alzheimer’s Network, or DIAN. He sought to enroll four hundred people who came from families with the mutation, though they didn’t have to be carriers to participate—siblings like Karla, who did not carry the gene, could still serve as controls. Participants would undergo cognitive testing and neurological exams, donate blood and spinal fluid for testing, and have their brains scanned to measure physical structure as well as any amyloid deposits. After they died, DIAN scientists would study their brains at autopsy.

  Morris wanted to know: What were the first abnormalities to appear in the brain of an Alzheimer’s patient? How long before symptoms of dementia appeared did that happen? What biomarkers changed when, and in what sequence? By answering those questions, which mirrored the ones Reiman and Tariot were asking, Morris hoped to better pinpoint the optimal time to intervene with drugs.

  He also wanted to compare the pathologies between mutation-triggered and run-of-the-mill Alzheimer’s disease, to see how comparable the rare form was to the one that was stalking the general population. If they were able to find a drug that helped the mutation carriers, that comparison would theoretically help predict whether that success might cross over for everyone else.

  “We know the mutation carriers are going to develop symptoms,” he said. “Everyone sees the power of intervening.”

  Because of its size, Morris’s study would set the stage for clinical drug trials, and he already had a team in place. The trial segment of DIAN would be led by Randy Bateman, a distinguished professor of neurology at Washington University’s School of Medicine, as its principal investigator.

  DIAN would grow to span fourteen research centers: three in Australia, one in London, two in Germany, and eight in the United States. Starting in 2012, one of those sites would be the University of Pittsburgh, and Bill Klunk’s Pittsburgh Compound B would be used for the amyloid brain scans at all the sites. Through their relationship with Klunk, the DeMoes were also able to enroll in DIAN, thus expanding their research contributions internationally. Some DeMoes would be too far advanced in their disease state to qualify for the drug trials; but they encouraged their children to enter.

  • • •

  With her firstborn gone and her second son now living in a nursing home, Gail was growing increasingly more fragile, though she still had good days. She continued her lifelong habit of jotting down poems and ditties, and once she learned how to navigate her home computer, she became adept at social networking. A regular haunt of hers was Facebook, where even her grandchildren’s friends wrote to her. Off-line, her own friends continued to drop by the house, just to check in and socialize.

  On bad days, without the responsibility of caring for Doug, she did not get dressed or get out of bed. If she was awake and lucid enough to speak when Karla called to check on her, she talked about Brian.

  “It’s hard on that old lady,” said Brian’s son, Yancey, and he was right.

  But the stress was also getting to Karla, who did what she could to help her mother from across the state. She set Gail up with a life-call service in case she fell and needed assistance while Dean was at work. She arranged for a housekeeper. She worked tirelessly, and even when Matt and her children told her to slow down, she could not. One of their rooms was filled with documents related to Alzheimer’s to help her keep track of her family’s journey. And though she usually managed to talk about her siblings matter-of-factly, she sometimes became overwhelmed at the thought that one day they would all leave her, and she would be the lone survivor of what had been a large and thriving family. She was not sure she would be able to function when that happened.

  The most reliable help for Gail came in the form of Chelsey Determan, who adored Jamie’s mother. In fact, the two women—young mother and great-grandmother—became the closest of friends. Gail was enchanted with Savannah, her youngest grandchild, and often referred to her as “the apple of Grandma’s eye.” She kept tea sets for her in Karla’s old bedroom, so they could have parties; Gail kept Savannah for sleepovers, and the little girl grew into a precocious little spitfire with a butterscotch-colored ponytail, like her father in appearance but far more confident. When she visited her uncle Dougie in the nursing home, she played easily with all the elderly residents; she had none of the shyness that children sometimes display around old folks.

  Chelsey looked after Gail as though she were her own mother, fussing over her prescriptions, pitching in whenever she was needed. She made the time.

  Gail called her a godsend.

  • • •

  Jamie worked long hours and remained characteristically worried about life, but he doted on his little girl, calling her by her nickname, Nanna. He tried to be strict with her but was often disarmed by her sass. When he visited the University of Pittsburgh to contribute to the DIAN study, he and Chelsey always brought Savannah along with them, and she was a favorite among the staff there.

  When a psychiatrist interviewed Jamie about his life, asking him what he did to keep busy, he didn’t know how to answer.

  “You mean besides work?” he said. The truth was, not much. He was assigned to a rig that operated around the clock. Depending on where it was located, he sometimes put in a fourteen- to fifteen-hour workday, and his schedule placed him on the rig two weeks in a row, then off two weeks. He was earning a six-figure salary, and it was helpful that he never had to schedule vacations, but it was brutal, dirty, exhausting work—not to mention dangerous.

  But even during the spans when he had two straight weeks off, Jamie struggled to occupy his time. He blamed the oil boom for ruining Tioga’s small-town atmosphere.

  He didn’t really talk about it much, but Chelsey could tell he was depressed. She also thought she detected some subtle lapses in his memory. You had to be around him daily to really sense it; he didn’t get lost, didn’t forget major events, nothing like what Brian and Doug were experiencing when their emp
loyer flagged them.

  Depression is extremely common in Alzheimer’s patients, particularly in the early stages of the disease. The National Institute of Mental Health established formal guidelines for diagnosing depression in someone with Alzheimer’s, reducing emphasis on verbal expression but including irritability and social isolation.

  Chelsey and Jamie had known each other for six years, but “if you ask Jamie, he always says three. It’s fine,” Chelsey said, laughing her rich, deep laugh. By now, an engagement ring winked on her finger, but they hadn’t set a date. Nobody was really sure when, if ever, they’d actually marry. “Always. It’s always ‘three.’ ”

  But sometimes, he had trouble recalling other details, too. Like their first night in Pittsburgh on that trip, when they’d taken Savannah to a Pirates game; they’d left before the end and watched the final inning on the hotel TV, but Jamie hadn’t recalled that the next day. Or the trip they’d taken to the Minot State Fair: They had driven in and met up with a friend, but Jamie thought for some reason that they’d all driven there together.

  He’d never been great about following story lines in movies or television shows, and he was tired all the time. He was never overly happy. Dean had told him he’d still be the same person, and he wanted so much to believe that. He longed to return to the man he had been before the diagnosis: the one who’d had the guts to persuade Chelsey to dance, who broke hearts across town and could party with his nephews Yancey and Tyler just as easily as he could with his older brothers. He just didn’t know how to get back to that place in his life.

  The research specialist asked Chelsey if circumstances were growing more difficult. Could she rate her own stress levels on a scale of one to ten?

  “You can have a lot of stress, just dealing with it,” said Chelsey, and her voice caught as she struggled to hold back tears. “I talk to Jamie’s mom a lot.”

  She wondered if antidepressants would help Jamie, but she knew he would resist taking them. Like Dean, he eschewed medication. He didn’t even drink much.

  While antidepressants are one treatment for depression in Alzheimer’s patients, researchers have found that other approaches—support groups, reengagement in favorite activities, celebrating small successes, exercise—also make an impact. Jamie said he would try. Reassuring the patient that he would not be abandoned was also important, and Chelsey made it clear that she would stand by him.

  • • •

  For the first time since his arrival at the research center three days before, Jamie finally relaxed when he settled into the big recliner they kept in the lab where they’d be scanning his brain. His arms were covered in bruises from all the needle sticks; one of the nurses apologized for how much trouble she had putting an IV line in his arm.

  “Don’t tell Chelsey or Savannah,” he said, referring to the chair, because he wanted it all to himself. Then he remembered: They couldn’t come in here, anyway.

  He was in the Positron Emission Tomography (PET) Research Center, part of the Department of Radiology at the University of Pittsburgh School of Medicine. Because she was only five years old, Savannah was banned from the center; the research team was concerned about her exposure to radiation. In fact, Jamie wasn’t allowed to hug her or pick her up after his brain was scanned with PiB and a radioactive form of glucose; he might still be shedding radiation. As a precaution, the research team had booked a second hotel room for Savannah and Chelsey to share, and Jamie would sleep alone.

  PiB clung to the amyloid accumulating in Jamie’s brain; the research team compared those physiological findings with the results of his written cognitive tests, answers to questions, and physical examination. They also measured how each part of his brain metabolized the radioactive glucose.

  A staff member wheeled a canister down the hallway from the room where they’d manufactured a dose of PiB in Chet Mathis’s beloved cyclotron. When the cyclotron was not in use, they covered it with a protective tarp; a cafeteria was located directly overhead, and syrup from the soda fountain had once dripped through the ceiling onto the cyclotron, giving Mathis fits.

  A technician, his hands coated in gloves, removed the freshly made PiB from its canister and injected it into the IV line that had finally been placed in Jamie’s battered forearm. Jamie squeezed his eyes shut and grimaced. He hated this part, hated feeling abandoned in the scanner. He asked if someone could please check on him every fifteen or twenty minutes, so he at least had some point of reference to know how much longer he’d be there.

  He’d made the same request the previous year, and nobody remembered to do it.

  “Sometimes it feels like you’re in there for hours,” he said.

  For most of the DeMoes, the research visit was an act of pure altruism. They knew they would not benefit from what they were doing—they were already past the point where experimental drugs might help them. That was part of what made their commitment so admirable: They didn’t have much time left, perhaps only a handful of years at best—and they were still giving so much of it up to advance the science beyond their life spans. In Dean’s case, he was taking time off from work that he needed to earn money for his family after he was gone. As symptoms advance, Alzheimer’s patients struggle more with travel. For Lori, each visit significantly and permanently subtracted from her ability to reorient herself once she returned home, and her symptoms worsened with each trip. Nothing deterred them.

  But for Jamie, the motivation was much more personal. In the few minutes before he had to climb into the hated scanner, he was thoughtful, almost philosophical.

  “You want to know why I do it?” he asked. “Probably a lot for Savannah, or maybe in my mind, that they’ll find a cure for me. It’s different for me, being ten years younger than Dean [sic]. I’m hoping maybe something—even not, maybe, a total cure, but something, maybe, where I could get five more years out of my life.”

  His best friend, Rikki Rice, knew the main reason Jamie wanted to buy time.

  “All he ever says about Savannah is that he hopes to see her graduate. If there’s one thing he talks about the most about the whole family disease, it’s seeing his daughter graduate from high school,” Rikki said as he sat at the Rig II bar in Tioga after a long workday. “His biggest fear is that he won’t be around, or not mentally stable.”

  Suddenly, the thought of what lay ahead overcame Rikki, and the big man sat in a bar filled with roughnecks, his drink on the table in front of him, and began to quietly weep.

  “I don’t want to see him like that,” Rikki said of his friend. “I don’t know how to prepare for it.”

  Twenty-One

  LANDSLIDE

  ON OCTOBER 28, 2012, the DeMoes’ cousin Dawn died at a Wisconsin nursing home. She was fifty. Though she had never been able to participate in the DIAN study, her brain was sent to the University of Pittsburgh, joining Brian’s, so she could posthumously contribute to a cure.

  Her daughters, Leah and Alayna, were part of the study; they wanted to do their part to combat the disease that had taken so much from their mother’s generation. But they refused to allow Alzheimer’s to change their life’s course. Leah had a second baby in 2015. Later that year, Alayna would also start a family. The way Leah saw it, some families have a predisposition to cancer, or heart disease, or diabetes. It wasn’t a reason to give up on life. She had fought too hard for this one. She vowed that she would be, to her children, the mother she never had.

  Her father kept reminding her to keep her mind on the present, not the future.

  “What’s wrong with twenty-five great years?” he asked. “Be grateful for the time you have, and then move on from there.”

  • • •

  Dawn’s sisters, Robin Harvey and Colleen Miller, were also part of the DIAN research cohort.

  Robin just adored the staff at the Alzheimer’s Disease Research Center, most especially Bill Klunk, who always seemed to be looking out for her best interest.

  Robin had known since 2006 that she
had inherited the Alzheimer’s mutation. She was saddened by Dawn’s death, but she had little contact with Leah or Alayna and nothing but contempt for her sister Colleen. None of them ever outgrew their sibling rivalry; if anything, it deepened as their troubles, compounded by the disease, continued to mount.

  Robin was married to her first husband long enough to have a son and daughter before they split up when the children were toddlers. A few years after her divorce, she met her second husband, Mike Harvey, with whom she had three daughters. But by 2004, that marriage also was dissolving.

  On a late July weekend in 2004, Mike took the three little girls—then eight, six, and four—camping on the Eau Claire River in Douglas County. It was a peaceful, lazy summer day until a piece of the riverbank crumbled under two of the girls, and they plummeted into the water. Frantic, their father dove in to save them.

  A group of high-school boys who had been idling on a nearby bridge pulled the girls to safety, but Mike and another bystander, who had also attempted to help, both drowned.

  Two years later, Robin learned she had Alzheimer’s disease.

  “I was hoping—usually, one in the family doesn’t get it,” she said, perhaps thinking of her cousin Karla. “I mean, I knew my mom’s mom had it, but I didn’t really think about it, you know? I was just living my life. . . . Yeah, I cried.”

  She was furious with Leah for refusing to get a genetic test before having a baby, and she wasn’t afraid to say so. She urged her own children to find out their mutation status before making that decision.