"Is what I'm experiencing ordinary midlife forgetfulness? Or do these memory lapses signify something more serious—like the first signs of Alzheimer's disease?"
Practically every day, someone asks me these questions. And I wish I had better answers. One evening, a white-haired gentleman rose to his feet in a jam-packed auditorium. Anxiously, he asked me to confirm that forgetfulness was a perfectly normal part of aging, without pathological implications.
That, to my sorrow, I could not do. Reluctantly, I told him what I knew. Every day, a new study rolls out of a university lab confirming that Alzheimer's isn't a disease that suddenly rears its head in old age. Current research shows that decades before clinical symptoms arise—in middle age or even before—the seeds of Alzheimer's are already planted. To insist otherwise is to indulge in the most unhealthy sort of denial.
Like the rest of our bodies, our brains change as we get older. Proteins that were once smoothly soluble begin to aggregate, impeding communication between neurons, resulting in mild forgetfulness. For many of us, that's where it stops. But in others, those same tiny proteins get out of control, triggering the development of dense plaques and tangles that surround neurons, infiltrate them and eventually strangle them. Today's scientists are working hard to develop a test that will show—at the earliest possible moment—who’s taking the wrong fork in the road.
The goal of nearly every Alzheimer's researcher is to find a way to identify the beginning of the disease process. "If we can meet this disease in the earliest stage and counteract it with drugs that reverse the damage, science would no longer be in the position of needing to build new neurons," says John Q. Trojanowski, director of the Penn Institute on Aging and Alzheimer's Disease at the University of Pennsylvania. "It is in your forties, or maybe even younger, that normal memory loss begins to diverge from pathological memory loss. In my lab, we’re spending a lot of time trying to define that fork in the road, where you either continue to lose a little bit of your memory capacity each year, and remain essentially normal, or you take the other fork, where you are on a downward trajectory, culminating in dementia."
Trojanowski's lab at Penn is on the leading edge of the hunt for a biological marker—the equivalent of a pregnancy test—for Alzheimer’s disease. This "biomarker" must be fast, painless, inexpensive and able to pick up indicators of the disease at a very early stage, permitting early diagnosis, before neurons begin to die. In order to know whom to treat, it's essential to know who is vulnerable. As part of a National Institute of Aging investigation, the Alzheimer's Disease Neuroimaging Initiative, or ADNI, Trojanowski’s lab has made significant progress in tracking down a marker for the elevated presence of tau and amyloid beta proteins in cerebrospinal fluid. It's accurate, and meets most of the criteria, but is of limited use in a once-a-year doctor's check up, since not many of us would like to top off our annual physicals with a spinal tap.
That's why people got so excited earlier this week when scientists at Stanford University announced that they had developed a blood test that can diagnose Alzheimer's disease years before memory loss is evident. The test shows a 90 percent accuracy rate in its ability to predict who would develop Alzheimer's disease two to six years in the future, by measuring eighteen proteins involved in cell signaling. The proteins that neurologist Tony Wyss-Coray assessed were not even on the list of "promising" blood chemicals identified in 2003 by the National Institute on Aging study—but often, that's how science works. For years, researchers pursue a hypothesis, adding bit by bit to existing knowledge—only to have another team of researcher turn that hypothesis on its ear and shout "Eureka, we’ve found it!"
The Stanford blood test, promising as it is, requires more extensive testing, in a larger sample of patients and control subjects, including confirmation of accuracy that can emerge only after the autopsies of deceased study participants. It will take several years to do these studies, and in the meantime, given the intense focus on this effort, other biomarkers in blood and urine are likely to emerge. That's good news for all of us. Within a few years, when you go to see your primary care practitioner, there will be one more box checked on the sheet you take to the blood lab—one that will tell your physician what’s going on in your brain. "It goes painful step by painful step," John Trojanowski emailed me, when I asked him what he thought of the Stanford news, "but this is progress that takes us closer to meaningful therapies."
For more on biomarkers, go to Carved in Sand Chapter 1, Your Unreliable Brain, and Chapter 18, Do You Really Want to Know.