About 1 million people a year begin a mental slide called mild cognitive impairment, or MCI, with forgetfulness that's somewhere between healthy aging and Alzheimer's disease. Now this gray zone is undergoing an evolution, with growing study of techniques to help predict which MCI patients may be on a path to later dementia - and who shouldn't worry.
Many doctors aren't waiting. A study published in the journal Neurology last week found 70 percent of neurologists say they prescribe Alzheimer's medications to at least some of their MCI patients, hoping the drugs will slow their decline. That's a startling number considering there's no proof yet the drugs can do that even if doctors knew who's most at risk.
And a study published this week adds to earlier evidence that spinal taps can detect a pattern of Alzheimer's-linked proteins in cerebrospinal fluid that may help diagnose Alzheimer's and predict who's at high risk for it. Belgian researchers reported in Archives of Neurology that they found the pattern in 90 percent of the Alzheimer's patients and 72 percent of the MCI patients in their study - but how to get accurate spinal tap measurements remains a big controversy.
So, it's becoming more and more clear that Alzheimer's starts ravaging the brain at least a decade before memory problems appear. Thus stalling it may require treating the earliest symptoms, just as preventing a stroke begins with treating high blood pressure.
But to discover an early-stage therapy requires first discovering whose MCI really is pre-Alzheimer's.
So when the National Institute on Aging and the nonprofit Alzheimer's Association proposed new guidelines for diagnosing both full-blown Alzheimer's dementia and that confusing MCI, they went an extra step. The draft also offers a roadmap for researchers testing new technology to help separate out the different types of MCI.
On the list: experimental PET scans that check for abnormal brain buildup of an Alzheimer's-linked gunk called beta-amyloid. Bollesen, 78, is getting that and other brain scans at the Mayo Clinic in a large study hunting for patterns that predict progression.
The retired teacher gets embarrassed by his main MCI symptom - forgetting the names of longtime colleagues - but says he doesn't worry about getting worse.
"They haven't told me what I can expect in the future. ... I'll think about it when they bring it up," says Bollesen, 78, of Rochester, Minn. If he does worsen, he figures the researchers "may have ideas of things I could be doing to delay it."
Here's the rub: Those technologies are becoming more available for use outside of strict research studies. Already, doctors at specialized medical centers can use MRIs to measure shrinkage of a brain region called the hippocampus. They can give spinal taps to look for that gooey amyloid in cerebrospinal fluid.
Soon, even the full-brain amyloid scans will be more available, says Dr. David Bennett, director of Rush University Medical Center's Alzheimer's program in Chicago.
Patients "want to know what's going to happen to them," says Bennett, who tries to redirect patients already demanding those test, or anti-Alzheimer's medications, into clinical trials.
Scientists haven't proven when a bad test result really means brewing disease, or even if you can believe a bad test result. Those spinal fluid measurements, for example, can vary as much as 30 percent from one sophisticated laboratory to another, says Dr. Marilyn Albert of Johns Hopkins University.
"The last thing in the world you want to do is tell someone they're destined to have Alzheimer's dementia when they're not," cautions Albert, who co-authored the draft guidelines and doesn't want doctors jumping the gun.
And just harboring amyloid alone doesn't mean pending dementia, as autopsy studies suggest a quarter of elderly people who die without memory problems may harbor the buildup, adds Mayo's Dr. Ron Petersen, who helped to first define MCI.
"Would I like to have amyloid in the brain? No, not particularly but it doesn't necessarily mean I'm going to become clinically demented in my lifetime," Petersen says.
For now, diagnosing MCI requires a good medical history and standard memory tests. MCI is more than every so often losing your car keys or struggling for a word, but not serious enough to interfere with independent functioning. Worsening of episodic memory - recalling new information - is seen more than other types of memory loss in MCI that progresses to Alzheimer's, say the draft guidelines, which will be finalized later this year.
Like so many with MCI, forgetting names sent Mac McNellis of Chicago to the doctor nine years ago. He feared the dementia his mother had suffered in her 90s, but he was relieved to learn he had MCI. McNellis enrolled in a study at Rush that scans his brain annually, and researchers advised mental and physical exercise.
Now 85, he plays golf and cards, and is a pro at sudoku and intricate woodworking. Then last fall, he experienced a new MCI symptom - getting frustrated in unfamiliar places - and began an Alzheimer's drug in hopes of slowing further decline.
"I just go with the flow," McNellis says.
But his wife, Gerry, says learning about MCI early was a big help.
"Staying active was probably the most important thing," says Gerry McNellis. "Fear of the unknown I think can really be detrimental. If you have an idea that there are some things that can be done within your own power, it's really helpful."
Alzheimer's Association study info: