Missing Memories

Doctors are all too familiar with the final stages of Alzheimer's disease, when neurodegenerative plaques and tangles spread throughout the brains of their patients, robbing them of memory, dignity and finally their lives. But what if there were a way to halt this terrifying decline? What if scientists developed a treatment that could somehow stop Alzheimer's disease in its tracks and prevent any further deterioration? Chances are you'd want to treat folks as soon as possible, in the earliest stages of the disease, long before devastating brain damage had occurred.

Researchers at Washington University School of Medicine in St. Louis, Mo., last week disclosed what may be an important step toward that goal. No, they didn't announce a new therapy that can stem the ravages of Alzheimer's disease. Instead, in a study that was published in the March issue of the Archives of Neurology, they provided compelling evidence that a condition called mild cognitive impairment, or MCI, which is characterized by repeated lapses in short-term memory, is in fact in many patients the earliest stage of Alzheimer's disease.

Should the Washington University findings hold up, they could eventually provide drug companies with another target for treating or even preventing Alzheimer's. Perhaps more immediately, however, the results could trigger all sorts of financial and legal headaches if, for example, insurance companies start labeling mild cognitive impairment as a pre-existing condition that disqualifies patients from long-term health-care coverage. This is apart from the emotional trauma of patients realizing that they probably have an incurable disorder.

In any event, the research underscores the fact that as scientists increase their knowledge about the earliest manifestations of Alzheimer's disease, more questions are being raised than can be answered. For instance, what exactly do researchers mean when they talk about mild cognitive impairment? "There are lots of conditions that can be subsumed under the term," says Dr. John Morris, lead author of the study. MCI could stem from the side effects of taking too many medications, a blow to the head or the lassitudes of depression. But what Morris and others are focusing on is repeated problems with short-term memory that are often first noticed by a close friend or relative.

This clinical view of MCI deals with distinct changes in forgetfulness over a period of a year or two--changes that can be verified with psychological testing. "People start at different points," says Neil Buckholtz, chief of the dementias branch at the National Institute on Aging. "Everybody forgets where they put their keys. But if you forget what keys are for, that could be a concern."

There is also preliminary evidence suggesting that a diagnosis of MCI can be confirmed with a magnetic-resonance scan of the brain. Typically, in cases of what turns out to be pre-Alzheimer's MCI, these images will reveal that the hippocampus, a central portion of the brain associated with short-term memory, is somewhat smaller than normal or even rather shrunken in appearance.