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Evelyn C. Granieri is that rarest of 21st-century doctors: she still makes house calls. On a warm Thursday morning toward the end of August, the New York–based geriatrician, outfitted in a tailored white suit and high heels, rang a doorbell at a seven-story red-brick apartment building in the Riverdale section of the Bronx and was buzzed in.

“You look gorgeous!” the doctor exclaimed when she greeted her patient, a 99-year-old woman with white hair and a wry smile, in the dining room of her apartment. In an hourlong conversation, Mrs. K (as we’ll call her) recalled, in moving and sometimes mischievous detail, growing up in Poland, where soldiers on horseback took her brother away; coming to America on a ship and working in her parents’ grocery store in Queens; and dealing with male colleagues in the real-estate business when they got “fresh.” But when Granieri asked how old Mrs. K was when she got married, she looked puzzled.

“I can’t remember,” she said after a pause. A cloud passed over her face. “Was I married? To whom?” A framed photograph on a nearby table memorialized her 50th wedding anniversary.

Spirited and funny, her personality intact even as her memory deteriorates, Mrs. K is one of more than five million Americans with dementia. Far from the gleaming research centers where scientists parse the subtle biochemical changes associated with Alzheimer’s disease and other forms of the condition, clinicians like Granieri, chief of the Division of Geriatric Medicine and Aging at Columbia University Medical Center, confront its devastating reality every day. And, often, they talk to relatives of patients. As Granieri and two interns probed Mrs. K’s memory with small talk and measured her blood pressure, a niece called from Manhattan to see how her aunt was doing.

Almost every dementia patient has worried family members huddled in the background, and almost every story about dementia includes a moment when loved ones plead with the doctor for something—any medicine, any intervention, anything—to forestall a relentless process that strips away identity, personality, and ultimately the basic ability to think. Unfortunately, Evelyn Granieri is the wrong person to ask. In 2010 she served on a high-level panel of experts that assessed every possible dementia intervention, from expensive cholinesterase-­inhibiting drugs to cognitive exercises like crossword puzzles, for the National Institutes of Health; it found no evidence that any of the interventions could prevent the onslaught of Alzheimer’s. She can—with immense compassion, but equally immense conviction—explain the reality for now and the immediate future: “There really is nothing.” Dementia is a chronic, progressive, terminal disease, she says. “You don’t get better, ever.”

These conversations have always been difficult for doctors and families alike, but perhaps never more so than in the past year, when public reports about dementia research have bounced between optimism and gloom. In the fall of 2011, financial analysts were giddily projecting a global Alzheimer’s market of $14 billion a year by 2020 and touting a new generation of drugs known as monoclonal antibodies that were in advanced human trials. A year later, the prospect for the drugs no longer looked so positive. This past August, the giant drug makers Pfizer and Johnson & Johnson suspended advanced clinical trials of one of the monoclonals because it showed no effect in patients with mild to moderate Alzheimer’s. A few weeks later, another leading pharmaceutical manufacturer, Eli Lilly, announced inconclusive results for a monoclonal drug it too was testing against the protein deposits called amyloid plaques that are characteristically found in the brains of Alzheimer’s patients. The disheartening results prompted some critics to start writing epitaphs for the prevailing hypothesis about the disease—that these amyloid deposits are causing the cognitive impairment.

“The field is in a precarious place right now,” says Barry D. Greenberg, director of strategy for the Toronto Dementia Research Alliance, “because tens of billions of dollars have been invested in the development of new treatments, and nothing—not a single disease-modifying agent—has been identified.” Granieri often sets off on her house calls from her second-floor office at Allen Hospital—literally the last building in Manhattan, on the northernmost tip of Broadway. That may sound like an out-of-the-way outpost in medicine’s battle against dementia, but in reality it sits at ground zero for the looming medical and societal catastrophe. The hospital’s catchment area includes upper Manhattan and parts of the Bronx, one of the three densest concentrations of nursing home facilities in the entire United States, according to Granieri. “Here we sit, right in an epicenter,” she says.

The epicenter is a contentious place these days. Frontline clinicians like ­Granieri are increasingly frustrated with the narrowness of dementia research. In the patients they treat every day, they see a disease that is complicated and insidious, often with multiple causes and murky diagnostic distinctions. In contrast, they see a research enterprise focused on several favorite hypotheses, and they see a drug industry that has profited handsomely from expensive, marginally effective treatments sought by desperate families.

Academic and pharmaceutical researchers, meanwhile, continue to throw money at the dementia problem—but finally, they insist, with better aim and much shrewder treatment strategies. They have begun to assemble a list of diagnostic markers that they believe may reliably indicate the first signs of Alzheimer’s disease 10 or 15 years before symptoms appear, and they are gearing up to test new drugs that can be given to healthy patients, in an attempt to block the buildup of amyloid long before dementia’s onset. Indeed, to hear researchers tell it, this summer’s highly publicized clinical-trial failures are already ancient history. They are finally doing the right kind of science and hope to get the right kinds of answers, the first glimpses of which may appear in the next several years.

As Granieri and other physicians who treat dementia patients know, the stakes could scarcely be higher.

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Credits: Galerie Beckel Odille Boïcos, William Utermohlen

Tagged: Biomedicine, memory, aging, Alzheimer's, dementia, Alzheimer’s Disease

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