Did the World Just Gain Hundreds of Millions of Alzheimer’s Patients?

The mood matched the spectacle. Joanne Pike, the Alzheimer’s Association’s president and C.E.O., announced that recent advances had brought the campaign against the disease to a “pivotal moment.” Maria Carrillo, its chief science officer, hailed a groundswell of progress. That optimism followed decades of disappointment. Between 1974 and 2020, the U.S. government spent roughly twenty billion dollars on Alzheimer’s research without seeing the approval of a single treatment designed to act on the disease’s underlying biology, let alone stop or reverse its course. Today, Alzheimer’s afflicts roughly one in nine Americans over sixty-five and, along with related dementias, has been estimated to cost the economy about three-quarters of a trillion dollars a year. In surveys, it ranks with cancer as the disease people fear most. That’s understandable. Alzheimer’s dismantles the self by degrees. It typically starts by robbing patients of recent memories—conversations they just had, where they put important objects—before corroding the basic functions of adult independence, from paying bills to managing medications. Eventually, it leaves patients unable to speak, move, swallow, or recognize close relatives. “We estimate a man by how much he remembers,” Ralph Waldo Emerson wrote, about a decade before an Alzheimer’s-like dementia left him scarcely able to write his name. But at the conference many seemed to think that the disease could soon join scurvy and smallpox in the annals of yesterday’s afflictions. That excitement is widely shared. In June, Bill Gates had posted about “a golden age of Alzheimer’s research.” These high hopes rest largely on two developments. First: drugs. Since 2021, the Food and Drug Administration has approved three antibody treatments meant to slow the disease’s progression. All target amyloid, a protein fragment that can accumulate into the plaques that have long been associated with Alzheimer’s and that many researchers believe plays an important role in its development. Two drugs—lecanemab, sold as Leqembi, and donanemab, sold as Kisunla—are on the market and are covered by Medicare. The second development concerns diagnosis. Until recently, measuring amyloid levels in living patients required expensive PET scans or invasive spinal taps. Blood tests developed over the past five years approach the accuracy of those methods. The F.D.A. cleared the first such test in May, 2025; three more have followed. “For the first time,” Gates wrote, “we have simple blood tests that tell you whether you have Alzheimer’s.” A disease that could once be confirmed only after death is now, in Gates’s telling, as easy to detect as high cholesterol. Combined with drugs that promise to slow deterioration, such tests are raising hopes of achieving a long-sought goal: treating prospective patients early enough that symptoms never appear. The result has been to give new urgency to one of the most fiercely debated questions in contemporary medicine: What, exactly, is Alzheimer’s disease? Kewman was adopted as an infant, and his concerns about Alzheimer’s began in 2016, when he signed up for genetic testing through 23andMe. When his results came back, he was given the option of learning his genetic risk for late-onset Alzheimer’s. “Of course, being a curious guy, I said yes,” he told me, his hazel eyes alert behind brow-line rectangular glasses. It turned out that he carried two copies of a gene called APOE4, making him much more likely than the average person to develop Alzheimer’s dementia. “It took a while to sort of absorb that information,” he said. Several years later, he was informed that his brain contained a moderate accumulation of amyloid plaques. Alzheimer’s, he told me, is “at the bottom of my desirable ways to die.” A Quaker from the age of seventeen, he worries less about what it might do to him than about what it might mean for his loved ones. He and Sandy do not have long-term-care insurance, and he knows that the disease can impose “a terrible burden on family,” one that “can deplete your assets pretty dang fast.” Sandy spent more than twenty-five years as an intensive-care nurse and understands the difficulties that could come with the disease. Yet Kewman remains cognitively normal. “We’ve taken care of our bucket lists and keep making bucket lists,” she said. When I asked him whether he thought of himself as having Alzheimer’s, he paused. “It’s a good question,” he said. “I have some of the changes associated with Alzheimer’s disease.” He meant the amyloid deposits. “So, in some sense, I do.” He quickly qualified his answer: many people with those changes never develop the “full-blown disease,” with its deterioration of “memory, behavior, functioning, independence.” I asked Sandy the same question. “No,” she said. Not long ago, most physicians would have agreed.

“What month is it now?” “The eleventh.” “What is the name of the eleventh month?” “The last one, if not the last one.” “Which one?” “I don’t know.”

At times, Deter seemed to recognize what was happening to her. “So anxious, so anxious,” she said when Alzheimer asked whether his questions were difficult. Told to write the number 8, she repeated, “I have lost myself, so to say.” Deter never left the asylum. Her speech deteriorated into shouts and hums and eventually almost disappeared. She died in 1906, roughly five years after Alzheimer first saw her. By then, he had moved to Munich, but he had her brain sent to him. Examining it, he detected three abnormalities: deposits of a substance, later identified as amyloid beta; tangles of fibrils inside neurons, now known to be composed largely of tau proteins; and a reduced number of neurons. In Deter, features that would become closely associated with Alzheimer’s appeared together: amyloid plaques, tau tangles, and profound cognitive decline. Both amyloid beta and tau are normally present in healthy brains; the plaques and tangles are abnormal aggregations of these molecules. At the time, however, Alzheimer’s disease did not mean what it does today. When Emil Kraepelin, Alzheimer’s supervisor, named the condition in the 1910 edition of his influential psychiatry textbook, he conjectured that it differed from dementia, then the catchall term for cognitive decline in old age. Although Kraepelin recognized that plaques, tangles, and neuronal loss could also occur in the ordinary dementia of old age, he noted that Alzheimer’s patients were unusually young, sometimes in their forties or fifties, and that their illness could take an especially severe course. For much of the twentieth century, “Alzheimer’s disease” was therefore virtually synonymous with “presenile dementia.” It was not until the nineteen-seventies, more than sixty years after Kraepelin named Alzheimer’s disease, that it came to encompass late-onset dementia. The figure most responsible for this was Robert Katzman, a reserved, soft-spoken neurologist who chaired the department at the Albert Einstein College of Medicine, in the Bronx. In the nineteen-sixties, his mother-in-law developed confusion and memory problems. She was sixty-four—just below the conventional cutoff for senile dementia—and so she was diagnosed with “presenile dementia,” or Alzheimer’s disease. The line struck Katzman as suspiciously arbitrary. “It became obvious that Alzheimer’s disease was a single entity regardless of age of onset,” he later recalled. Medicine had a powerful model for deciding that apparently different illnesses were really one disease: identify a common cause. In the nineteenth century, the physician Robert Koch showed that pulmonary consumption, intestinal disease, and swollen lymph nodes could all result from the same bacterium, Mycobacterium tuberculosis. In a two-page editorial published in 1976, Katzman argued that some instances of early- and late-onset dementia should be grouped together as Alzheimer’s disease. His evidence was chiefly descriptive. Both could involve plaques and tangles. He could not show that a single causal process produced both conditions, as Koch had done with tuberculosis. But the shared features, he maintained, were enough. In 1977, Katzman, Butler, and others convened a conference at the N.I.H., in Bethesda, in part to settle the question of classification. Katzman remarked that he had expected “more argument,” but the participants seemed to agree “that Alzheimer’s disease and senile dementia are one.” When the group discussed what to recommend to the American Psychiatric Association for the next edition of the Diagnostic and Statistical Manual of Mental Disorders, one attendee asked, “Does anybody here seriously believe they are two different diseases?” Three years later, the Alzheimer’s Association was founded; four years after that, the new definition of the disease was formally codified, when six experts, including Katzman, published the first widely accepted diagnostic criteria for the disease. These criteria remained centered on symptoms. A diagnosis of “probable Alzheimer’s disease” depended primarily on progressive cognitive decline, particularly memory loss. Plaques and tangles could confirm it, but only after death. Although the diagnosis covered a much larger population, a living patient still had to show cognitive impairment to qualify. Back then, researchers would have had no way of knowing about Kewman’s amyloid deposits. All they would have seen was a cognitively normal person—by their criteria, someone without Alzheimer’s. Then, in 1984, researchers at the University of California, San Diego, isolated the main component of the plaques that Alzheimer had first observed: aggregations of the peptide now known as amyloid beta. Months later, the same group identified a similar protein fragment in the brain of a person with Down syndrome, a condition linked to an unusually high risk of Alzheimer’s-like pathology and dementia. The discoveries helped elevate amyloid from a hallmark of the disease into a possible culprit. In 1992, the molecular biologists John Hardy and Gerald Higgins proposed what became known as the “amyloid-cascade hypothesis.” Amyloid, they argued, was the “causative agent of Alzheimer’s disease.” Its accumulation, in their account, triggered tau abnormalities, killed neurons, and produced dementia. The hypothesis soon became the leading model of Alzheimer’s. Its champions, branded Baptists for their emphasis on beta-amyloid deposits, marshalled plenty of supporting evidence. Rare inherited mutations that virtually guaranteed early-onset Alzheimer’s affected the production of amyloid. People with Down syndrome carried an extra copy of the gene for the amyloid precursor protein. These observations suggested that when amyloid accumulated more readily, Alzheimer’s would follow. The therapeutic strategy seemed obvious: remove amyloid. If that worked, a treatment would be of enormous commercial value. The excitement spread widely. “A cure for Alzheimer’s might be within the grasp of researchers,” New Scientist announced. Elan quickly began testing its vaccine in people. In 2002, however, the trial was halted after some participants developed meningoencephalitis, a dangerous inflammatory condition. Meanwhile, drugmakers explored a related approach: supplying the antibodies directly. They infused patients with laboratory-made monoclonal antibodies, or mAbs, designed to bind to amyloid and help clear it. The approach would eventually produce lecanemab and donanemab. For years, though, it failed. The first anti-amyloid antibody tested in large clinical trials appeared to affect amyloid but did not slow cognitive decline. MRIs also revealed, in some patients, brain swelling and microhemorrhages. (These were given the benign-sounding name “amyloid-related imaging abnormalities,” or ARIA—which feels as abstruse as calling a knife wound a “blade-related imaging abnormality.”) Other antibodies, such as gantenerumab and crenezumab, were also abandoned, after faili