Broader definition of Alzheimer’s could help doctors diagnose it earlier

For the first time in 27 years, health authorities have expanded the definition of Alzheimer’s disease.

The change, announced last week by the National Institutes of Health and the Alzheimer’s Assn., is intended to help doctors diagnose patients in the very early stages of the neurological disorder, including those who have yet to develop any outward symptoms. The new approach could ultimately help millions of older Americans spend more years with their mental faculties intact.

By the time a patient becomes demented, it is “too late” for medications to be of any help, says William H. Thies, chief scientific and medical officer of the Alzheimer’s Assn. in Chicago. So researchers are trying to develop drugs that could slow the progression of the disease, for which there is no cure.

“If we start 10 years earlier and could push off the appearance of dementia by, say, five years … that could cut the number of demented people in the U.S. by half,” Thies says. “That would be an amazing public health accomplishment.”


But it won’t happen immediately. Two large clinical trials of compounds intended to stave off the worst stages of the disease both failed.

For now, experts acknowledge, the new diagnostic criteria will probably mean that more people will receive the grim news that Alzheimer’s is in their future — and there won’t be anything they can do about it.

“There is nothing that can be done for them, not yet,” says Creighton H. Phelps, director of the National Institute on Aging’s Alzheimer’s Disease Centers Program.

For now, agrees Dr. John M. Ringman, interim director of UCLA’s Easton Center for Alzheimer’s Disease Research, “it doesn’t change how we treat patients.”

Alzheimer’s is characterized by severe memory loss, as well as impaired reasoning and judgment, personality changes, loss of problem-solving ability and a host of other mental problems. Thirty years ago, the condition was diagnosed primarily by excluding all other forms of mental disorders. A definitive diagnosis could be made only after death, when an autopsy of the brain would reveal the abnormal amounts of amyloid proteins forming plaques and tau proteins forming tangles.

By that criteria, there are an estimated 5.4 million Americans with Alzheimer’s disease now, and that number is expected to grow to 16 million by the middle of the century as increasing numbers of baby boomers mature into the over-65 age group that is most vulnerable to the disease.

Unlike the old guidelines, which recognized only full-blown Alzheimer’s, the new ones recognize two earlier stages of the disease: mild cognitive impairment, which means some symptoms of the disorder have begun to appear; and preclinical Alzheimer’s, in which biochemical and physiological changes linked to the disease have begun but symptoms have yet to appear.

The changes reflect the sharply increased knowledge about the disorder that scientists have accumulated over the last two decades and the development of new tools that allow diagnosis of the disease to be made much earlier in the course of its development.


In the last 10 years in particular, researchers have made remarkable progress in identifying biological changes that accompany Alzheimer’s disease. These include imaging studies with MRI scans that show shrinkage in specific areas of the brain associated with Alzheimer’s and the appearance of characteristic proteins, called biomarkers, in the spinal fluid of patients with the disease. Researchers have also found genes that are associated with increased susceptibility.

These studies showed that Alzheimer’s is a slowly progressing disease that begins as much as 20 years before full-blown symptoms develop.

Some very limited studies suggest that there are at least 1½ times as many patients with mild cognitive impairment as there are with end-stage Alzheimer’s, and perhaps two to three times as many, Thies says.

“The scary part of this whole thing is the idea of preclinical Alzheimer’s disease. That really got my phone buzzing” with calls from concerned patients, said Dr. Peter Davies, director of the Litwin Zucker Research Center for the Study of Alzheimer’s Disease at the Feinstein Institute for Medical Research in Manhasset, N.Y.


Even though these patients are identified, there is little that can be done for them.

There are two families of drugs that are now used to treat end-stage Alzheimer’s: acetylcholinesterase inhibitors, including Aricept, Razadyne and Exelon, and another drug, memantine, that blocks certain receptors in the brain. “All only address symptoms and don’t interrupt the course of the disease,” Phelps says.

Researchers have completed two randomized placebo-controlled clinical trials of medicines that looked like they might be able to block progression of the disease if caught early. One of the trials tested ginkgo biloba — a popular herbal extract that many people take for its supposed ability to enhance cognitive function — and found that it provided no benefit. The other trial involved non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, but it was stopped early because of side effects from the drugs.

Researchers are now attempting to figure out how to organize clinical trials of both the existing drugs — which might prove more useful when the disease has not progressed very far — and new ones in people with preclinical Alzheimer’s and mild cognitive impairment.


Meanwhile, the new tests and criteria should help prepare patients for the worst, Ringman says.

“People want to know what they should tell their children, whether they should take that world cruise they’ve been planning all their lives right now or wait five years,” he says. “This will be helpful in counseling them.”