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A new line of attack on Alzheimer’s

Redefinition of illness could speed research

PUSHES EARLY DETECTION Alzheimer researcher Reisa Sperling said a shift in thinking is needed to find disease- modifying treatment. PUSHES EARLY DETECTION
Alzheimer researcher Reisa Sperling said a shift in thinking is needed to find disease- modifying treatment.
By Chelsea Conaboy
Globe Staff / April 19, 2011

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Alzheimer’s disease cannot be clinically diagnosed until it begins to lay waste to a person’s mind, a vexing reality for those who study it, suffer from it, or care for a loved one. Within a decade, that could change, according to scientists who today released a new definition of the disease.

Researchers are on track to develop tests that can identify Alzheimer’s in the brain before a loss in memory and reasoning abilities. Better detection could lead to more effective treatment.

The new definition, the first since 1984, says that Alzheimer’s does not begin with dementia. Instead, it is a long, degenerative process that starts years before symptoms emerge.

By redefining the disease, scientists hope to provide a framework to expedite research into the causes and treatment of Alzheimer’s.

The definition, published online as four papers in the Alzheimer’s Association journal Alzheimer’s & Dementia, includes a road map designed to guide scientists in their pursuit of tools for early diagnosis.

That focus “is the shift we need to make if we’re really going to get to disease-modifying treatment,’’ said Reisa Sperling, lead author of one paper and director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital in Boston.

The new definition includes a preclinical stage in which damage caused by a buildup of an abnormal protein in the brain called beta-amyloid might be detectable before symptoms begin. Researchers who are hunting for better ways of finding and treating Alzheimer’s are using high-tech snapshots to identify its earliest signs. Those medical scans are not in routine use today, but could foreshadow future diagnostic techniques.

One doctor compared the situation to a time decades ago when blood pressure was not part of a regular medical exam. Instead, the first evidence of hypertension was a stroke or heart attack.

The goal is to develop tests for reliably measuring those early signs of Alzheimer’s and how or whether they will lead to disease. Just as someone who has precancerous cells may not develop cancer, patients who show early biological signs may not develop Alzheimer’s, Sperling said.

Individual risk factors, including genetic predisposition and family history, determine how quickly the disease progresses in a patient, she said.

The intention, said William Thies, chief medical and scientific officer for the Alzheimer’s Association, is to “develop drugs that will prevent that early pathology from causing catastrophic symptoms of full-blown disease.’’

The Alzheimer’s Association estimates that 5.4 million people in the United States suffer from the disease. By 2050, the number could rise to 13.5 million, and Medicare costs will exceed $1 trillion, according to a report the group produced last year.

Alzheimer’s can be diagnosed definitively only with an autopsy, and the few drugs that exist do little to slow the disease.

The best that patients can hope for today is that a shrewd doctor will recognize mild changes in cognitive functioning, such as decision making, as the first warning signs.

The authors of the new definition, funded by the association and the National Institute on Aging, said they hope doctors will start looking earlier for those signs.

Diagnosis of mild cognitive impairment has grown in the past 10 years, but the definition was “wishy-washy,’’ said Robert Stern, director of Boston University’s Alzheimer’s Disease Center Clinical Core.

The new definition lays out clearer parameters, but says more work needs to be done to develop biological tests.

“That’s a real diagnosis, and you shouldn’t just chalk that up to normal aging,’’ Stern said.

Early diagnosis is key to helping families cope and connecting patients to clinical trials, said Stern, who is a member of the medical and scientific advisory committee for the regional chapter of the association, but was not among the scientists who developed the new definition.

Early detection also raises a difficult ethical question for physicians and patients: What is the point of knowing early about Alzheimer’s if there is nothing that can be done about it?

Thies provided an example he said demonstrates the importance of early diagnosis. There are two business executives he knows who have early Alzheimer’s.

One was diagnosed quickly. When he could no longer work, he became eligible for disability and retained much of his salary.

The other was not diagnosed. His impairment affected his job, and he got fired. Now, he and his family are managing his care on limited Social Security income.

“Would you plan your life differently, plan your finances differently, if five years before you were going to become demented you knew that was coming?’’ Thies said.

Research is catching up, said Sperling. There are drugs being tested now that could slow the production of abnormal proteins that form in the brain or even clear them, she said.

The trouble is timing.

“We’re just starting too late in the disease,’’ she said.

Chelsea Conaboy can be reached at cconaboy@boston.com.

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