The Inheritance

by Niki Kapsambelis

  “In some ways, it was kind of a relief to him to know,” his wife said. “I think he didn’t feel like he had to hide things and pretend everything was all right.”

  Jerry and Sharon had always been practical, and they jumped into action as soon as they got home. He took early retirement from OSU Tech; they arranged for retirement and disability payments. They also purchased a piece of property in Beggs, Oklahoma, that was large enough to create the family compound Jerry had long dreamed of. In earlier, happier times, they had imagined they would grow old in the country, surrounded by the laughter of their grandchildren. But now there were practical reasons for the move: More family members would be nearby to help as Jerry required more care.

  “He never showed to me how hurt or worried he was,” Sheryl recalled. Her father remained upbeat, as he always had been. Just as he had once fed the needy, he thought of his disease as an opportunity to help other people; he wanted to participate in research to help find a cure.

  The drug the NIMH recommended for Jerry, tacrine, was the first ever approved by the FDA that had been developed specifically to treat Alzheimer’s symptoms. Sold under the brand name Cognex, it was a cholinesterase inhibitor, which prevents the breakdown of a chemical called acetylcholine, which aids memory, thinking, and reasoning.

  • • •

  Cognex followed a circuitous route before it got to Jerry DeMoe, since federal regulators did not exactly welcome the drug with open arms. In 1991, an FDA advisory committee rejected Cognex, saying its side effects—including liver damage—outweighed any small benefit it might offer. Although its inventor, a California doctor named William K. Summers, had claimed that Cognex dramatically helped Alzheimer’s patients and downplayed the side effects, the FDA cast doubt on his research methods and conclusions.

  For the Warner-Lambert company, which had hoped to market Cognex, this setback was devastating. At least one investment analyst estimated that the drug would have been worth $1 billion in annual sales.

  But the disappointment didn’t last long. Two years later, the FDA reversed itself, and the advisory board said despite the side effects and questionable benefits, the drug should be available to patients because they basically had no other options. At least one panel member called it “a matter of conscience.”

  Summers, who took a sabbatical to promote the drug’s approval to the FDA, hailed the reversal as a vindication, calling it “a great day for Alzheimer’s patients and their families.” He predicted that once ordinary doctors got their hands on Cognex, the world would see the amazing benefits he had reported in his studies. Jerry DeMoe began taking the drug in 1995.

  But Jerry never saw the improvements that Summers promised. Plaques and tangles continued to collect in his brain, and his symptoms continued to worsen.

  Soon after the diagnosis, Sharon made herself a vow: She would care for Jerry at home, and would never send him away, as Gail had done with Moe. When they moved to the new property in Beggs, Sheryl, who was now fourteen, would start at a public high school to free up Sharon’s time for her husband. It was a scary transition for Sheryl, a shy child who wasn’t sure what to expect from her new home or her new school. And she was saddened to leave their old house, where she had spent every holiday, birthday, and family gathering of her young life. She described it as “a pretty and sweet season of my life, gone.”

  Jerry was still well enough to drive his daughter to school, but his speech was becoming difficult to understand; it was one of the first major pieces of his character to disappear.

  As she watched Jerry working on his old GMC truck, tinkering with his tools, Sheryl saw his frustration. A simple sentence—I’m going outside—would turn into “a long, exhausting guessing game,” she said. He compensated by poking fun at himself when he forgot a word, trying to laugh away the embarrassment, the way his North Dakota family might have. Though she had told herself she would stick by him, Sheryl grew impatient and began spending less time with her dad and more with the new school friends she eventually made.

  “I knew this was one of the stages of the disease, but I hated it,” she would later write. “This wasn’t my dad, he was perfect, and this man can’t even talk normal. What happened?”

  As the difficulties of her own teenage years took hold, she began withdrawing from both of her parents, often acting selfish and rude.

  She hoped for the impossible, that one day her father would go to the doctor’s office and learn that the drug he was taking had stopped his disease. Every night she prayed: Please make him better.

  It never happened. When their church held a laying-of-the-hands service to heal him, Jerry had his only moment of clarity in what felt like years, and became very emotional. Sharon was deeply moved by the service. But Sheryl, a skeptical adolescent, was frustrated that God had not yet cured him.

  Outwardly, her parents maintained their composure. Her mother asked her to talk about her feelings, but Sheryl shut her out. What she didn’t know was that privately, Jerry’s vast reserves of positive thinking were rapidly being depleted; to his wife, he talked about suicide. Behind her composed façade, Sharon was thinking about it, too. She turned to her faith to carry her through. When she spoke to God, her request was simple.

  “I mostly wanted help; how to help him, and how to help the situation,” she said. “My prayers became shorter, and I was desperate.”

  Gail called to offer her support. To Sharon, it was a lifeline, even when they didn’t talk about the disease. They laughed and joked; Gail believed in using humor to relieve some of the emotional burden.

  “We knew the pain. I knew what she felt, and she knew what I felt,” Sharon said. “It was someone who I knew understood completely.”

  As Jerry’s disease progressed, he became irritable and angry, as had his brother before him. He spent a lot of time in front of the television. Jerry’s grandchildren adored him; they called him “J-Pa” (Sharon was “Meemaw”). Though he had once loved children, their noise and commotion began to irritate him.

  At the same time, Sheryl was consumed with shame over how she was treating her parents, but she couldn’t seem to break free of it; every day, her father only got worse. The Cognex had not slowed down the Alzheimer’s progression, and it was apparent that he was fighting a losing battle. He tried to fling open the car door when his wife was driving; he ran away from church. Sometimes, he hid outside their house where Sharon could not find him.

  Miserable at home, Sheryl found solace in the company of her boyfriend. In January of their senior year in high school, he proposed; he even asked Jerry and Sharon’s permission to marry their younger daughter. Jerry was lucid enough to give his blessing. Like her cousin Karla before her, Sheryl married the man she had been dating since eighth grade.

  In August 2000, a radiant eighteen-year-old Sheryl wore a sleeveless white gown, one hand carrying a bouquet of yellow roses, the other hand tucked in the crook of her proud father’s arm. Lori McIntyre made the trip to see her young cousin’s wedding. But when the preacher asked Jerry the traditional question—“Who is giving this woman in marriage?”—he could not find the words to answer. His wife said them on his behalf, then helped him sit down.

  Before the couple left on their honeymoon the next day, Jerry pulled his new son-in-law aside to say, “Take care of my little girl.” A dozen years and four babies later, the thought of it still makes Sheryl cry.

  • • •

  After Sheryl moved out, Jerry became more aggressive, more bewildered. As had been the case so many years ago with his uncles—Wanda DeMoe’s brothers, who questioned their own images in the mirror—he became angry at his reflection, so Sharon covered all the mirrors in the house with sheets. It felt as if they were mourning him already, a Jewish family sitting shiva for the dead. He confused his wife with Wanda, his late mother. Sometimes, angry and belligerent, he grabbed her, but Sharon was not afraid. It was not until he failed to recognize her as anyone but a stranger that she finally broke down.


  She wished she could detach herself from her husband enough to send him to a nursing home, the way Gail had, a decision she now understood better. And while many people described Gail as one of the strongest people they had ever met, Sharon wasn’t so sure.

  “I know how that goes. You can really make people believe that,” she said. “I know there were weaknesses, but she hid them well.”

  Although Jerry comprehended less and less as time went on, he was aware enough of his surroundings to feel the sting when the neurologist in Tulsa who had been running his tests for the research trials determined that his contributions were no longer useful; he had deteriorated to the point where he couldn’t answer questions. He was devastated by the idea that he could no longer help.

  “He really wanted to do something,” Sharon said. “In his mind, that was very important, and I know it is to all of the DeMoes. That was a setback.”

  The problem came to a head when, at one appointment, the doctor entered with an unfamiliar colleague and startled Jerry; Sharon slid in front of him, but it was too late to prevent Jerry from getting agitated and upset. The doctor, who was worried about his own safety, called security and suggested a psychiatric ward.

  Sharon froze, not knowing what to do, and they took Jerry away and dosed him with Haldol, a powerful antipsychotic. She had no idea what her rights were, or how to advocate for him.

  “They completely knocked him out,” said Sharon. “He didn’t even do anything. I mean, I could have handled it. I don’t know what the doctor thought. They wouldn’t let me get him out.”

  She went to visit him, a newly pregnant Sheryl in tow; he asked to be taken home, but the hospital hadn’t released him yet. To distract him, Sharon turned his attention to their daughter.

  “Sheryl’s here. Isn’t she getting fat?” Sharon teased.

  Not understanding the joke, Jerry gave his wife a dirty look. But Sheryl’s laugh relaxed him, and they explained.

  She was having a boy, Sharon said. Jerry was finally going to get his boy.

  • • •

  When Jerry was released, instead of placing him in an institution, Sharon brought him home and found another doctor. That arrangement worked briefly, but the ugly truth about Alzheimer’s, of course, is that it never gets better. It can be contained and controlled for a while, sometimes for months, sometimes for years; but in the end, the disease always wins, and the symptoms boil over, burning whoever is attending the pot. Sharon would learn, as many caregivers do, that it’s not a question of love or devotion or commitment. Finally, she caved and called a nursing home.

  Her intent was to have him stay there for two weeks, just enough time for her to rest. She was exhausted. But then he tried to escape and was moved to a different facility. He asked to come home.

  By the time Sheryl and her husband welcomed their son on June 21, 2002, and brought him to meet his grandfather, Jerry didn’t even know they were there.

  After a brief hospital stay, Sharon contacted a hospice, installed a hospital bed in their living room, and brought him home.

  “I thought he was going to live for years like that, and I was willing to take care of him that way,” Sharon said. “I don’t know if I was in denial. Nobody really sat me down and told me that he was really bad . . . I thought I’d rather have him sick than not at all.”

  In total, Jerry DeMoe lasted at home for only about ten days. Years before he ever developed Alzheimer’s disease, he and Sharon had discussed their end-of-life wishes; neither of them wanted life support or to be resuscitated when their time came.

  One night, Sharon pulled her air mattress beside the bars of his hospital bed.

  “I wanted to get in bed with him, just lay beside him,” she said. “I climbed in there. Well, I couldn’t get out. I weighed more than he did at the time.” She laughed fondly at the memory. She had eventually struggled her way out. “But I got to cuddle him a little, anyway,” she said.

  Thinking about this man she had loved her entire adult life, she still felt the unspoken magic that had brought and kept them together.

  “He was a sweet guy; he was caring. He was macho and masculine, but yet he had a soft heart and cared about people,” she mused. “I was a spoiled brat, actually. I don’t know how he put up with me, because he wasn’t that way.

  “I guess he loved me.”

  • • •

  On September 17, 2003, Sharon called Sheryl to say: Come home. It’s time to say good-bye.

  Numb, Sheryl was unsure what to expect. It wasn’t like the movies; there were no comforting final words, no peaceful deep sleep. There was only a shell of her father, once so vibrant and loving. She wanted to tell him how sorry she was for how she had acted toward him for all those years.

  At some point, in those final hours, she did hold his hand. It was cold and skinny, not the warm, strong grip of the man who’d held her as a little girl. She could not make herself speak; she hoped that he felt her love through that hand.

  Nine

  THE FRUITS OF PERSISTENCE

  BY 1995, HAVING isolated three autosomal dominant mutations that guaranteed Alzheimer’s disease—APP, PS1, and PS2—science had a small group of patients who could potentially offer some clues about the way the disease developed. With a simple blood test, doctors could identify that a person had one of the mutations and was definitely going to get the disease.

  In the years that followed, time became the chief roadblock to finding a prevention therapy for Alzheimer’s. The standard approach would be to gather thousands of volunteers, including healthy people; give them experimental treatments and placebos; then see what drugs budged symptoms in people who ultimately developed dementia. But that process required too many healthy volunteers, too much money, and too many years—longer than the life of most drug companies’ patents—to achieve any meaningful results.

  Such trials were attempted. The National Institutes of Health conducted its Alzheimer’s Disease Anti-inflammatory Prevention Trial, nicknamed ADAPT, on twenty-four hundred elderly volunteers beginning in 2001. Participants were given anti-inflammatory drugs, and the study’s research team tracked them to see whether the medications cut down on the risk of Alzheimer’s after age seventy. Concerns over cardiovascular side effects sidelined that study in 2004, but the participants were followed for seven more years before researchers concluded that the drugs didn’t help them. Meanwhile, as a generation of baby boomers continued to age, a tidal wave was building. Science couldn’t afford to wait.

  • • •

  In addition to the logistical problems facing the field, a debate began brewing among scientists over the key mechanisms responsible for the disease. On one side, which became the prevailing view, researchers believed that an excess of beta-amyloid protein caused the disease. This theory gained traction after UC San Diego pathologist George Glenner detailed the structure of beta-amyloid in 1984. Since Alzheimer’s patients had plaques forming outside their brain cells and beta-amyloid was the plaques’ main ingredient, a hypothesis formed that beta-amyloid played an important part in the disease’s development. The fact that genetic mutations led to overproduction of beta-amyloid seemed to support this theory, and in time, scientists who adhered to it were nicknamed the “Baptists” (for the first initials of beta-amyloid protein).

  But the other side argued that neurofibrillary tangles forming inside the brain cells, and not plaques, were the primary culprit. This group was called the “tauists,” after the tau protein, the chief ingredient in the tangles.

  In a healthy brain, cells receive nutrients through a transport system made up of structures called microtubules, which run in parallel lines that look like railroad tracks. The tau protein, which normally has some phosphate molecules attached to it, binds to the microtubules and stabilizes them to keep everything running smoothly.

  In an Alzheimer’s brain, an abnormally high amount of phosphate molecules attach to the tau, causing it to break off from the microtubules and attach to
other tau threads, forming tangles inside the cell. Without tau, the microtubules disintegrate, and the cell becomes unable to communicate with other neurons. Eventually, the neuron dies. With it die the connections networking it to other neurons and the synapses that transport memories. When enough cells die, the affected parts of the brain begin to shrink.

  Regardless of whether amyloid or tau was the primary disease trigger, researchers also faced another major obstacle: Nobody had any way to look at Alzheimer’s in a living brain. They had to wait until the patient died, then examine brain tissue during an autopsy.

  That made perfecting any kind of drug treatment maddeningly difficult. In order to stop the disease, scientists needed to track the way it developed so they could try to predict its path and test treatments. Without being able to see the brain’s response to the drugs, neurologists wouldn’t be able to pinpoint what was and wasn’t working. If they could figure out a way to fix their brain-imaging problem, researchers would be able to watch the disease unfold in real time, which would help them narrow their approaches for drug therapy.

  But basic biology was working against them. The body’s natural filtering system, known as the blood-brain barrier, prevents most substances (including anything with an electron charge) from crossing into the brain through a series of tightly joined cells.

  • • •

  In 1994, this was the challenge facing Chet Mathis, a radiochemist at the University of Pittsburgh who specialized in developing compounds to image the brain. He’d arrived there two years earlier because the university had a well-respected medical school stocked with psychiatrists who were itching for someone to help them create images of serotonin and other neuroreceptors, which are the chemicals the body produces to communicate information throughout itself. Today Mathis speaks reverently of the school’s dedicated cyclotron—a one-hundred-ton, $2 million particle accelerator used in physics—the way other professors speak of perks like parking spaces and posh faculty clubs.