The Forgetting Page 6

  If Khachaturian was correct, and the average duration of the disease was set to more than double, then the problem would be even worse than epidemiologists were predicting. Either way, it was clear that if Alzheimer’s disease was not conquered reasonably soon, it would become one of the most prominent features of our future. Nationally, the number of nursing home beds would at least quadruple. (The stay of Alzheimer’s sufferers in a nursing home is, on average, twice as long as that of other patients.) We would need vastly more home health care workers, elder-care nurses and physicians, assisted living facilities, day-care programs and support groups. (There was already a grave shortage of qualified professional caregivers—and, due to the low pay, a shocking annual turnover rate of 94 percent.) Family leave would also have to be redefined. Progressive nations would likely adopt a system of employee flexibility for senior care (extended leave, flexible work hours, and so on) similar to the one recently implemented for new parents in the U.S.—with the added caveat that revene parenthood lasts significantly longer and is more draining than conventional parenthood.

  All this would cost money, and would require a painful shift in resources away from other public needs. Public officials would be forced into difficult decisions. Would the U.S. government, for example, continue to allow an Alzheimer’s patient to give away all assets to his children in order to qualify for government-sponsored care? Would governments require citizens to have some sort of dementia or frailty insurance?

  And what about public safety issues? With as many as fifteen million people suffering from insidious (and largely invisible) cognitive decline, how would we insure street and highway safety without automatically invalidating all driver’s licenses of senior citizens?

  There was a dual race on, then. Researchers were racing against one another, and against time. The prize for the winner of this race—if there was to be a winner—would be worldwide fame, nearly unparalleled professional esteem, enormous wealth, and the pride of knowing that you were personally responsible for preventing an ocean of future human suffering.

  One glimpse into the magnitude of an Alzheimer’s cure: In the nearly fifty years since Jonas Salk and Albert Sabin introduced their vaccines against polio, somewhere between 1 and 2 million lives have been saved. Curing Alzheimer’s disease sometime in the first decade of the twenty-first century would save as many as 100 million lives worldwide in the same length of time.

  The far-flung researchers kept in touch by E-mail, phone, and fax, and accomplished much in their labs spread out all over the world. Still, every so often, they needed to come together physically, to be in the same room to check their progress, to goad each other, critique and criticize each other, to energize.

  In 1999, the gathering place was Taos. They came from everywhere, a global convergence of neuromolecular intelligentsia sitting on fold-out chairs in Bataan Hall to share knowledge and probe their ignorance. There was still so much they didn’t know: Why are women more susceptible to Alzheimer’s than men? Why are Cree and Cherokee Indians less susceptible than the rest of us? What is it about the environment in Hawaii, as contrasted with Japan, that apparently doubles one’s chances of getting Alzheimer’s? Why do a third of Alzheimer’s victims develop Parkinson’s disease but not the other two-thirds? Why do some cigarette smokers seem to be less likely to develop Alzheimer’s than nonsmokers?

  After ninety-plus years, the field was littered with half-answers to these questions—and far more basic ones: Does Alzheimer’s have one cause or many? Is it really one disease or a collection of very similar diseases? Which come first—plaques or tangles? Why do they always originate in the same part of the brain? How long do they proliferate before they begin to affect brain performance? Why do some people accrue a brain full of plaques and tangles but never display any symptoms of the disease? Is anyone naturally immune to Alzheimer’s?

  So, humbly, they gathered. With respect for the vexing nature of this disease, the molecular biologists and geneticists spent thirty hours listening to theories of plaque and tangle formation, and intervention strategies. After each short talk, they quickly lined up behind a microphone in the aisle to poke the presenter with questions, looking for holes in the research and analysis. The tone was alternately respectful and suspicious, and occasionally hostile.

  Hostile because of the billions of dollars at stake, and also because of a fracturing debate within the community about which aspect of research mattered most. A nearly one-hundred-year-old question still had not been answered: Which are closer to the root of the problem—the plaques or the tangles?

  Alois Alzheimer thought it was the tangles. “We have to conelude,” he wrote in 1911, “that the plaques are not the cause of senile dementia but only an accompanying feature.”

  Most, however, now said the plaques. In a field where there were so many open questions and possible approaches, the vast majority of researchers in this room and elsewhere were focused tightly on the issue of plaque formation, while relatively few were concerned with tangles and only a handful of others busied themselves with important issues like inflammation, viruses, and possible environmental factors.

  The disparity bothered many. “When I was a little girl, I wanted to go into science because I thought it was a very open community,” Ruth Itzhaki, a biologist from the University of Manchester, told me one morning in Taos. “I learned better. It is, in fact, a very cynical community layered with politics and filled with people who just want to follow the herd.” Itzhaki was herself embittered by her struggle to fund research linking the herpes simplex virus 1 (HSV1) with Alzheimer’s.

  Could Alzheimer’s be herpes of the brain? It was not the most prominent theory of the day, but no one could rule it out. Nearly all humans are infected by HSV1 by the time they reach middle age. The virus mostly seems to lie dormant but can become active and create cold sores and other hazards in times of stress. Whether or not HSV1 does any damage depends largely on individual levels of immune response and on genetic makeup.

  In her presentation, Itzhaki said she had found evidence of HSV1 presence in the temporal and frontal cortex of the brain, as well as in the hippocampus—three areas closely associated with Alzheimer’s. She posited that the virus might be interacting with a particular gene to set the disease process in motion. If proven true, a massive new global infant immunization project would be in order.

  But the crowd in Taos did not seem very interested. Her talk drew little in the way of response. The focus quickly shifted back to plaques.

  One evening I got a telephone call from a friend. He was telling me what a tough day he’d had on the job; he’d made several mistakes. “If you have Alzheimer’s, I must have a double dose of it,” he said.

  I could feel myself entering a state of rage. “Do you forget simple words, or substitute inappropriate words, making your sentences incomprehensible? Do you cook a meal and not only forget you cooked it, but forget to eat it? Do you put your frying pan in the freezer, or your wallet in the sugar howl, only to find them later and wonder what in the world is happening to you? Do you become lost on your own street? Do you mow your lawn three or four times a day? When you balance your checkbook, do you completely forget what the numbers are and what needs to be done with them? Do you become confused or fearful ten times a day, for no reason? And most of all, do you become irate when someone makes a dumb statement like you just made?”

  “No.”

  “Then you don’t have Alzheimer’s,” I said, and hung up.

  —L.R.

  Lafayette, Louisiana

  Chapter 5

  IRRESPECTIVE OF AGE

  Late one night in the early 1950s, Meta Neumann, a neuropathologist at St. Elizabeth’s Hospital in Washington, D.C., got word that an elderly colleague of hers, the clinical psychiatrist Dr. P., had died. It came without warning. That very morning. Dr. P. had ably led a vigorous meeting of hospital staff.

  Situated on a three-hundred-acre campus across the Anacostia River in the southe
ast quadrant of the District, St. Elizabeth’s was at the time the premier mental hospital in the United States. It had been founded a century earlier, in 1855, the first national mental health facility, as part of a massive effort throughout the Western world to rehabilitate the mentally ill. By the mid-twentieth century, St. Elizabeth’s housed between seven and eight thousand patients. The poet Ezra Pound was confined there from 1946 to 1958 for his pro-Fascist broadcasts from Italy during World War II. In 1981, it became the home of John Hinckley, Jr., Ronald Reagan’s would-be assassin.

  St. Elizabeth’s also had the oldest pathology lab of any mental health institution, including an unmatched archive of twenty-three hundred brains taken from deceased residents. These preserved brains floated in formaldehyde inside large clear glass jars. For more than a decade, Neumann had been the curator of the brain bank, regularly adding specimens to it and using it for research.

  Now Dr. P.’s brain would become an unexpected addition to the collection. The morning after his sudden death, Neumann performed an autopsy on him. She was a specialist in neurodegenerative disorders, and so it didn’t take her long to notice something unsettling about the brain of Dr. P. It was badly sclerotic. The arteries in his brain were severely clogged with fatty deposits, much like heart vessels before a major heart attack.

  In itself, the cerebral arteriosclerosis was not unusual; indeed, Dr. P. had a classic case. What made it curious was that prior to his death he had not exhibited any of the symptoms of senile dementia. At the time, the medical establishment believed senile dementia—dementia in old age—was caused by cerebral arteriosclerosis, the slow buildup of fat in the brain’s arteries over time. Medical schools in the early and mid-twentieth century taught as gospel that there were two clearly distinct types of dementia, easily separated by the age of onset:

  Alzheimer’s disease—

  A very rare disease afflicting people in their forties and fifties, characterized by plaques and tangles. Cause unknown.

  Senile dementia—

  A relatively common condition affecting the elderly (sixties and older), caused by cerebral arteriosclerosis.

  Senile dementia was not regarded as a disease, just an unfortunate side effect of getting old. Few had questioned this distinction, but in Meta Neumann’s autopsy lab on that particular morning in 1952, it didn’t hold up. According to what she saw in his brain. Dr. P. should have died in a senile fog. But Neumann and her husband, Robert Cohn—also a neuropathologist at St. Elizabeth’s (they had met during an autopsy)—had spoken with Dr. P. just before his death, and found him to be perfectly lucid.

  If Dr. P. had fatty deposits in his brain, and he wasn’t senile, logic dictated that fatty deposits must not cause senility. So, Neumann wondered, what does?

  It was a question she could seriously explore on her own. With her own in-house brain bank, she had all the resources she needed at her disposal to examine a large number of cases of diagnosed senile dementia and see if the brains did, in fact, show sclerotic changes. She and Cohn began the hard dicing.

  Two hundred and ten brains later, her hunch was confirmed. Just as Neumann had suspected, few of the dementia brains showed sclerosis. Instead, they showed plaques and tangles. These were Alzheimer’s brains.

  Alzheimer’s was not a rare disease after all. It was the leading cause of dementia, by far, in people of all ages. “The clinical picture was the same,” says Cohn, “irrespective of age.”

  The question of what Alzheimer’s disease was, exactly, had been a great sad muddle for many decades, ever since Alois Alzheimer first shared details of his remarkable five-year interaction with Auguste D. as both patient and lab specimen. If the case of Frau D. was destined to be an important part of the history of neuroscience, it was impossible to tell by the initial hearing. Alzheimer discussed his findings at a regional conference for German psychiatrists in November 1906, where he was met with indifference. At the lecture’s conclusion, conference chairman Alfred Hoche, a leading psychiatrist from Freiburg, called for questions or comments. No one spoke a word. After a long silence, Hoche called again for questions. Again, nothing. Dementia, death, plaques, tangles—no one in the room seemed to much care. Hoche himself couldn’t even muster a comment as a courtesy. “So then, respected colleague Alzheimer, I thank you for your remarks,” Hoche said finally. “Clearly there is no desire for discussion.”

  But the following year, Alzheimer’s written report of the autopsy, “A Peculiar Disease of the Cerebral Cortex,” was published to a more enthusiastic audience: his boss, Emil Kraepelin.

  Kraepelin was the most ambitious and authoritative psychiatrist of the day. In his Handbook of Psychiatry, he published the first psychiatric nosology, or classification of diseases. By the early 1890s, it had become an international bestseller, a seminal text. Kraepelin published new editions every few years, and his colleagues regarded his updates and modifications with close attention. By the time of Auguste D.’s death in 1906, Kraepelin was nearly unrivaled in his influence, and not shy about using it.

  But Kraepelin was also a man in need. The radical contention of his Handbook was that a vast number of mental illnesses were actually organic diseases, with distinct pathologies. The trouble was, he had no proof—no recorded link between mental distress and the alteration of brain tissue. With no evidence to back up his claim, many of Kraepelin’s peers loudly doubted his central notion, arguing that brain diseases would never be so easily classifiable from the study of structural changes in the brain. At a 1906 conference in Munich, three prominent psychiatrists confronted him. “There can be no talk of nosological specificity,” insisted the distinguished Berlin academic Karl Bonhoeffer.

  Robert Gaupp, the new director of the University Hospital for Psychiatry and Psychotherapy in Tübingen, agreed, stating unequivocally, “No psychological symptoms can be explained from anatomical findings.”

  Alfred Hoche twisted the knife a bit further, poking fun at Kraepelin for what he saw as foolishness. “The search for illness types is a hopeless hunt for a phantom!” teased Hoche.

  Only Kraepelin’s protégé Alois Alzheimer came to his defense. He did so not only out of loyalty, but also because he had the perfect ammunition. “I can verify [this] anatomical doctrine,” Alzheimer told the critics flatly. “Twelve days ago, on April 8, a Frankfurt patient, Auguste D., died. I have had the clinical history and the brain sent to Munich, and I have undertaken to document in this case that there is indeed an anatomical doctrine.”

  Kraepelin’s most formidable rival, Viennese neurologist Sigmund Freud, was not at the Munich conference. Freud was fashioning the new school of psychoanalysis out of the proposition that an enormous number of mental problems were neuroses of the mind, not organic diseases of the brain. Where Kraepelin saw the brain as a cell-based organ at the mercy of biological processes, internal mishaps caused by what he called “autotoxins,” Freud saw it as a reservoir of thoughts and emotions that played off against one another and competed for dominance. Further, Freud insisted that mental health was not a simple matter of healthy vs. diseased, but more of a continuum. He saw no clear line of demarcation between emotionally healthy and emotionally sick persons.

  These competing views would eventually come to be embraced as dually legitimate and coexistent, but in the first decade of the twentieth century, Kraepelin’s organic psychiatry and Freud’s psychoanalysis were a pair of sumo wrestlers on a small bamboo raft: two ideologies aggressively competing for the hearts and minds of Central Europe. Co-existence was not considered acceptable to either side.

  Kraepelin wrote scathingly of Freud as early as 1899, sarcastically calling his ideas “highly remarkable conceptions” and dismissing what he and his colleagues saw as an obsession with sex. “If … our much-plagued soul can lose its equilibrium for all time as a result of long-forgotten unpleasant sexual experiences,” Kraepelin remarked, “that would be the beginning of the end of the human race.” To the organic psychiatrists standing with Kraepelin, Freu
d’s ideas were little more than Schweinerei—“smut.” In 1906, Walther Spielmeyer, one of Kraepelin’s colleagues, called Freud’s work “mental masturbation.”

  Freud responded with equal acidity. When Otto Gross, one of Kraepelin’s clinical assistants, wrote a book that attempted to synthesize both sides of the debate, Freud commented, “What interests me most about Gross’s book is that it comes from the clinic of the Super-Pope, or at least was published with his permission.”

  The critically important brain physiology vs. psychology debate was really just beginning, and would last through the twentieth century and beyond. Along the way, Alzheimer made a significant contribution. As both the physician at Auguste D.’s side and the pathologist examining her brain, Alzheimer established a direct link between her dementia and the plaques and tangles clouding her cortex. This wasn’t irrefutable proof of an organic brain disease, but it was the first solid evidence. “Alzheimer … offered a causal relation between neuropathological and psychopathological alterations,” says psychiatrist and historian Matthias M. Weber. “… For this reason, Alois Alzheimer was perhaps the most important coworker of Emil Kraepelin.”

  After Kraepelin read Alzheimer’s article, he immediately seized on the detailed descriptions and moved quickly to formalize the discovery. Grateful to Alzheimer for bolstering his organic doctrine, he probably also wanted to reward him. So he named the disease after him. In the 1910 edition of his Handbook, Kraepelin mentioned Alzheimer and his work numerous times before blurting out a surprising and indistinct reference to Morbus Alzheimer: