The Thief of Thought

by Nushin Rashidian

Lynn Peterson forgets things. When she couldn't recall the name of the restaurant where she and her husband celebrated his 80th birthday, she wrote down the name to remember it.

“I would look at that piece of paper and say, ‘Oh, look how simple that is,’” she says. “And then, in a few minutes, I would lose it again.”

Peterson, who’s 74 and lives in Upland, California, hopes that her memory loss will stop there. But her family doctor believes she's at risk for Alzheimer's, the form of dementia that took her older sister's life, and that nobody knows how to prevent or cure.

The many varieties of dementia, whose causes range from Parkinson's disease to a series of strokes, lead to memory loss and a host of other symptoms, including difficulty walking, visual hallucinations and tremors. Alzheimer's disease, the most common form, accounts for 60 to 80 percent of dementia cases and now afflicts 5.3 million Americans, a number projected to reach an alarming 13.5 million in 40 years.

“It is a rising tide, it's truly an epidemic, and you will become very aware of it,” says Guy Eakin, research director at the American Health Assistance Foundation. “If people don't think they know someone with Alzheimer's disease, they're wrong. They almost certainly do.”

Alzheimer's slowly and irreversibly destroys the brain’s ability to function. What causes the death of brain cells remains incompletely understood, but evolving imaging technology has provided some visible clues. The Alzheimer's-afflicted brain appears shrunken. In its folds, the two telltale signs of Alzheimer’s — known as plaques and tangles — form and spread. They appear first in the region responsible for memory creation, which explains why forgetfulness is an early warning. These red flags are evident, however, only after the damage is done.

“We don't have good enough biomarkers,” says neurobiologist Frank LaFerla, director of the Institute for Memory Impairments and Neurological Disorders at University of California, Irvine. Elevated cholesterol, he points out, serves as a warning for heart disease. But “we don't have that yet for Alzheimer’s where we can screen an individual before they have memory loss and say, ‘Hey, unless you change your habits, you're on your way to developing Alzheimer's disease.’”

LaFerla's team was the first to breed a mouse whose brain developed both plaques and tangles, a step towards understanding how and why they form. The researchers found that every human brain creates beta amyloid, the protein that leads to plaques. Normal brains discard it, but in an Alzheimer's patient, the proteins accumulate inside and outside the brain cells, forming plaques that resemble tiny Brillo pads.

One way plaques lead to tangles, LaFerla says, is that plaques cause inflammation. In response, the immune system becomes overactive, partly mitigating the problem, but also worsening it by causing phosphates to build up on the tau protein, which then twists and tangles.

“At one point, it was vehemently debated,” LaFerla says of this sequence of events, “but so much data is emerging that it's becoming much more accepted.”

What results is a progression that Ipsit Vahia, geriatric psychiatrist and researcher at the Stein Institute for Research on Aging at the University of California, San Diego, describes as “negative development.” People with Alzheimer's disease unlearn the things they’ve learned in reverse order — the most recent memories are the first to go.

But the brain’s degeneration does more than just ruin memory; it progressively impairs even the most primitive functions, such as swallowing, until the body finally stops functioning. With no reliable prevention or treatment, Alzheimer’s is always fatal; it has passed diabetes to become the sixth leading cause of death in the United States, and climbing.

The cost of caring for an Alzheimer's patient averages $33,725 a year, an amount that doubles when the value of unpaid care from family and friends is included. The total cost of care for all Alzheimer's patients this year will reach $172 billion, the Alzheimer's Association estimates; by 2050, it will top one trillion dollars.

“When you start thinking about the cost to our economy to both treat people and to care for them, and the amount of lost time caregivers have to endure,” Eakin warns, “we're really looking at staggering costs to the U.S. economy.”

Moreover, as 70 million baby boomers age and have unprecedented impact on the health care system, the nation will need 3.5 million more healthcare providers—including nurses, pharmacists, and physicians—by 2030, according to the National Academy of Sciences. The number of geriatricians will need to increase fivefold.

“We do not have the medical staff, we do not have the facilities, we do not have places to put these people,” says Ed Markin, research director at the Alzheimer's Research Foundation.

Yet the primary burden of caring for those with dementia still falls on family members, whose own health often suffers as a consequence. Caregivers are at heightened risk for problems like depression and high blood pressure. They lose hours at work, forgo promotions, sometimes leave their jobs altogether. It's a demanding, often lonely task to help people who still want to assert their competency and independence.

“This is a disease that costs an amazing amount to provide care to individuals, and part of that cost includes the caregivers’ time and stress,” says Colin Depp, psychologist and researcher at the Stein Institute. “It has a remarkable effect on the community in multiple ways, in reducing quality of life of the family.”

While nothing can yet cure Alzheimer’s, researchers are seeking treatments to slow its progression or stave it off. This summer's International Conference on Alzheimer's Disease shed some light on the importance of cognitive stimulation, LaFerla reports. His own research on cognitive stimulation shocked him: His team learned that it slowed the rate of memory decline in mice, and also reduced plaques and tangles. A recent human study shows that cognitive stimulation also slows cognitive decline in people, and LaFerla is hoping that participants will show reduced plaques and tangles as well.

In additional to behavioral experiments, LaFerla’s is overseeing researchers from several California universities as they experiment with stem cells to see if cell replacement could be a potential Alzheimer's treatment.

Now that scientists know more about the disease and its risk factors, and have animal models to study, they see reasons for optimism. Patients like Lynn Peterson, and their families, hold onto hope, too.

But Depp remains cautious in his predictions. One of the better outcomes, he says, would be keeping the number of Alzheimer's diagnoses where it is.

“Medicare will still be in trouble no matter what,” he says. “But I think there will be new treatments in the next ten years and hopefully they will lessen the impact of the increase. So, maybe we can get it to the point where it's as big of a problem as it is now.”

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