In 2006 former television journalist Meryl Comer described in the Alzheimer’s & Dementia journal what it’s like to care for a husband with early-onset Alzheimer’s disease. “At night I slip between the bed covers, careful not to disturb the stranger lying there,” she wrote. “Soon he will wake screaming and flailing his arms as if fighting off demons. … Exhausted, I drift off only to reawaken and find myself lying by his side in a pool of urine.” Eleven years earlier, before his diagnosis at age 58, Comer’s husband, Harvey Gralnick, had been chief of hematology and oncology at the National Institutes of Health (NIH). Now he was detached from reality and unpredictably violent. He knocked out her two front teeth once when she tried to bathe him—an incident she left out of her article. Comer clung to one hope. “Today,” she wrote, “the field is on the brink of major breakthroughs that may lead to more effective treatments and, ultimately, to prevention.”
Seven years after Comer wrote that article, things are worse. Her husband lingers on, protected at home from the secondary infections that kill many Alzheimer’s patients in nursing homes. Now her 93-year-old mother—who in 2006 was just beginning to exhibit Alzheimer’s-related paranoia—has full-blown symptoms and lives with her as well. Comer, who has been named president of the Geoffrey Beene Foundation Alzheimer’s Initiative, puts in 12-hour shifts caring for her husband and mother and spends $100,000 a year on home nursing care, none of it covered by Medicare. She expects to go bankrupt eventually.
Alzheimer’s disease remains incurable and 100 percent fatal. Because of modern medicine’s successes, more people are outliving heart disease, cancer, and stroke, only to be hunted down by Alzheimer’s and other forms of dementia. It’s hard to conceive of a worse way to die than to lose one’s mind. Asked last year in a Home Instead Senior Care/Marist Poll which disease they were most afraid of having, 44 percent of Americans named Alzheimer’s, as many as named cancer and stroke combined.
If nothing is done, Alzheimer’s will become the “financial sinkhole of the 21st century,” says gerontologist Ken Dychtwald, chief executive officer of Age Wave, a consulting firm. Already, treating dementia of all kinds costs more than heart disease or cancer, more than $150 billion a year in the U.S., including the value of informal care, according to a Rand Corp. study released on April 3. That number could more than double by 2040 as baby boomers age into the Alzheimer’s danger zone, Rand says. Compounding the economic impact, women, who provide most of the care, are often forced to drop out of the labor force.
A medical breakthrough could change everything, as it did with HIV/AIDS, which has gone from being a death sentence to a manageable illness. With Alzheimer’s, nothing of the kind is happening. Up until last year there were high hopes for a new class of drugs that sweep beta amyloid protein from diseased brains. The drugs reduced beta amyloid as advertised but didn’t improve patients’ thinking.
Alzheimer’s research funding at the NIH was 6 percent lower in 2012 than in 2009, when it was supplemented by economic stimulus funds. It’s falling an additional 4 percent this fiscal year because of sequestration. The NIH gives Alzheimer’s only 9 percent of the money it spends on cancer and 16 percent of what it spends on HIV/AIDS, even though it has made far more progress against those diseases.
The tight research budgets are discouraging “the bright young people who are making the greatest advances,” says Dr. Michael Shelanski, co-director of the Taub Institute at Columbia University Medical Center in upper Manhattan. There are lots of intriguing leads, but the success rate for the NIH’s National Institute on Aging (NIA) grant applications last year was just 16 percent, Shelanski says. “We’re spending more and more time writing more and more grant applications. And the person with the best ideas may not be the person who enjoys writing grants.”
Dr. Jang-Ho Cha, a neurologist with an M.D. and a Ph.D., quit basic research out of frustration. He was an associate professor at Harvard Medical School and Massachusetts General Hospital for 14 years until 2010. “In the first six months of 2009, I wrote nine grants. Each one is like writing a Ph.D. dissertation. None got funded,” Cha says. “I said to myself, ‘You just went 0 for 9. What’s your plan for the next year? Just take more shots on goal?’ ”
Cha jumped to Merck as a director of clinical research, overseeing drug trials. He’s still contributing to medicine—albeit not to basic research—and getting paid more for it. Plus, he says, “My hardest weeks at Merck are like my easiest weeks at Mass General.” His advice to Congress? “Science is hard. More money would absolutely help.”
A brain destroyed by Alzheimer’s disease looks like a shrunken, rotting cauliflower. At the microscopic level, fragments of beta amyloid protein form clumps called plaques that seem to block communication between neurons. Tangles of another protein called tau kill brain cells by preventing nutrients and other supplies from reaching them. The disease spreads through the brain, knocking out memory, then speech and thinking, and finally basic functions like swallowing. Nearly half of people aged 85 and up have Alzheimer’s. But the disease begins to do damage long before symptoms appear. By the time boomers who lose their keys are laughing nervously about having a “senior moment,” they might be on the path toward illness.
The failure of clinical trials last year made clear the need for radically new strategies against the disease. Most of the time, though, what seem like crazy ideas really are crazy ideas. It takes a high tolerance for failure to make the occasional breakthrough. And in an era of tight funding, the tolerance for failure is low.
Dr. Marc Diamond of Washington University School of Medicine in St. Louis blames “grossly inadequate” research funding for making the peer reviewers who judge grant applications overly cautious. He’s investigating whether the tau protein in Alzheimer’s is like the misfolded proteins called prions in mad cow disease. (Dr. Stanley Prusiner, who won the Nobel prize in medicine for discovering prions, is pursuing a similar idea.) “Initially we couldn’t get our papers published, and we couldn’t get funded,” Diamond says. For application review panels, the safe course is to reject out-of-the-box ideas: “If you say no 100 percent of the time, you’re going to be right 95 percent of the time,” Diamond says.
Dr. Richard Hodes, director of the NIA, says his agency understands Diamond’s gripe and is directing money to certain innovative ideas even when they don’t meet peer reviewers’ thresholds for funding. Also, instead of just waiting for grant proposals to come in, his organization is soliciting proposals for an ambitious new approach that goes beyond testing individual candidate molecules and looks instead at whether “interaction among multiple pathways” causes Alzheimer’s, Hodes says. Researchers are refocusing on pre-symptomatic cases and teaming up with researchers who study brain damage in athletes and veterans.
Politicians on both sides of the aisle claim to support more funding for research. President Obama is proposing to give the NIA $80 million more for Alzheimer’s funding in the fiscal year beginning Oct. 1; unlike past step-ups, the sum would become part of the base funding, not just a one-year infusion. On April 2, Obama announced he will seek $100 million for a BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative. Newt Gingrich made Alzheimer’s a signature issue of his campaign for the Republican presidential nomination last year. House Majority Leader Eric Cantor (R-Va.) argued in a February speech that “smarter federal investments in medical research” are key to containing long-term health-care costs.
It’s customary to warn that the U.S. risks falling behind in research, but in this case work in other countries is all to the good. A World Wide Alzheimer’s Disease Neuroimaging Initiative is coordinating research in the U.S., Canada, Western Europe, Japan, Australia, Taiwan, South Korea, Argentina, and China. “I really believe that if you look at the problem from many different angles, things will link up eventually,” says Hermona Soreq, who runs an Alzheimer’s research team at the Hebrew University of Jerusalem.
Nancy Reagan described Alzheimer’s disease in her husband as a long goodbye. “It’s not a long goodbye. It’s a day-to-day horror,” says George Vradenburg, chairman of USAgainstAlzheimer’s, an advocacy group. With no cure in sight, boomers are trying to dodge Alzheimer’s by eating fish and flaxseed and doing crossword puzzles—the 21st century equivalent of wearing garlic against the black plague. The only sure defense is a medical breakthrough. It can happen, but only if the world makes it a priority of the first order.