Recently revised guidelines for diagnosing Alzheimer’s disease would reclassify nearly all patients who are currently diagnosed with mild or very mild Alzheimer’s as having mild cognitive impairment (MCI), a new study finds.
The change may be confusing for doctors and misleading for patients and their families, says Dr. John Morris, a neurologist at Washington University in St. Louis.
Reporting in the journal Archives of Neurology, Morris finds that 99.8% of patients now diagnosed with very mild Alzheimer’s dementia would actually be considered to have MCI, according to the latest guidelines. Among patients with mild Alzheimer’s, 92.7% would be reclassified as having MCI.
Before the latest revisions were written, the diagnosis of MCI was limited only to people who had lapses in memory that were not serious enough to disrupt daily life. But that definition began to expand in recent years to include patients with other cognitive problems, including changes in learning or attention and other deficits in thinking.
That’s why the new guidelines for MCI, adopted last year by the Alzheimer’s Association and the National Institute on Aging now include the criterion of “independent functioning,” and that’s where things get tricky. The definition of a patient’s independent functioning may vary widely depending on the doctor, and people with MCI have a broad range of functional independence: a person who can do daily activities on their own would be considered to have MCI, for example, even if they have mild problems or need assistance with paying bills, doing taxes and cooking.
“I think the proposed new criteria were a somewhat premature,” Morris says of the blurry line between MCI and early Alzheimer’s dementia, especially since researchers haven’t yet come up with a definitive way to distinguish MCI from early Alzheimer’s, with, for example, a blood test or other objective measure.
Why is the distinction — or lack thereof — so important? First, not all patients with MCI go on to develop Alzheimer’s, but almost all cases of Alzheimer’s start with MCI. That means that some people diagnosed with MCI may never progress to the serious cognitive declines that characterize the disease. For those whose impairment is likely due to early Alzheimer’s, however, it may do the patient and the family a disservice to call it MCI instead of dementia.
Part of the problem, Morris says, may have arisen from social and cultural factors as much as medical ones. In the study, Morris says doctors acknowledged being reluctant to diagnose patients with “dementia,” and he suspects that’s because they are afraid of scaring patients and robbing them of hope. MCI serves as a more neutral-sounding alternative, and physicians feel it’s more palatable to their patients.
Second, the MCI diagnosis does not include any consideration of what might be driving it — it’s a broad category that in some cases could include patients with Alzheimer’s-related memory problems, or in other cases, additional causes such as vascular problems. This means that studies looking at the beginnings of Alzheimer’s in people with MCI may include a mixture of true Alzheimer’s patients as well as those with other conditions, which may skew the results of, for instance, new drugs being tested.
That’s a particular concern since Alzheimer’s experts are increasingly focusing on the early stages of the disease. The latest evidence suggests that even drugs that have failed to help more advanced patients may be more effective during the first stages of the condition, before buildup of proteins and breakdown of nerves in the brain become irreversible.
In Morris’s study, he applied the new criteria to 17,535 people with normal cognition, MCI or Alzheimer’s disease and found that nearly all of those who in the past who would have been considered to have the first stages of very mild Alzheimer’s would now have MCI.
Medically, the fuzziness between MCI and early Alzheimer’s may result from the way doctors currently diagnose the conditions. In most cases, the decision is based on results from a single point in time. Doctors testing patients for cognitive impairment will frequently give them a battery of tests during one visit, and rate the patients as having either MCI if they only show problems in memory and don’t report any interference in their every day lives, or early Alzheimer’s if they score low on several cognitive tests. They then compare these results to those of people without cognitive problems who are otherwise similar to the patients. But this one-time snapshot doesn’t reveal much about what might be driving the changes in cognitive function.
Instead, Morris argues that older patients should be monitored for longer periods of time, and doctors should conduct more in-depths interviews with patients’ family members who can report changes in behavior and mental functioning. “It takes time and experience, but it is possible to come up with an accurate assessment of figuring out the underlying cause of MCI in patients,” he says. By faithfully recording any changes reported by people who are familiar with a patient and how his mental abilities have changed, he and his team regularly interpret whether a patient’s memory problems are potentially Alzheimer’s related or not. “It’s possible to make a diagnosis as accurately as if the person were more impaired with more obvious signs of Alzheimer’s dementia,” he says.
The key is to compare a patient to his own results over time, and not to test results from a national sample of adults, however similar they are, says Morris.
Ideally, a definitive test that detects the first signs of Alzheimer’s proteins would be able to distinguish Alzheimer’s-related MCI from MCI that’s due to other causes, and researchers are currently working on such screens, using blood tests and images of the brain.
But until those become available, many patients diagnosed with the type of MCI that progresses to Alzheimer’s may not be able to take advantage of drugs that are generally reserved for more advanced patients. Some doctors are already prescribing such medications for MCI patients, but again, there’s a lot of variability in how strongly doctors feel about dispensing them, since the drugs are only moderately effective, if at all, in slowing down the symptoms of cognitive decline. “I do think that defining MCI related to Alzheimer’s better will allow us to use therapies at an earlier stage of the disease,” says Morris, “but I can’t argue very vociferously because unfortunately current medications provide only modest benefit for patients.” Hopefully, new treatments will emerge along with better ways to distinguish the MCI that progresses to Alzheimer’s, and patients will be able to benefit from both.