After a diagnosis of mild cognitive impairment (MCI), it’s common for people to ask their doctors, “OK, so what drug is going to help me fight this thing?” Unfortunately, as they soon learn, there are currently no medications approved in the US for the treatment of MCI. However, that’s not all there is to the story. There’s more to know about the role of medication in the treatment of cognitive impairment and about other, non-pharmacological therapies for MCI.
MCI is a state of cognitive impairment more severe than to be expected from normal age-related memory loss but less severe than dementia, which is defined as impairment significant enough to interfere with daily living. Several medications have been approved for treating dementia, but none for MCI. Why is that?
It’s certainly not for lack of trying. In recent decades, researchers have conducted trials on a wide array of substances targeted at treating MCI, and several such trials are currently ongoing. So far, none of these drugs has proved effective at slowing or reversing the disease, or at improving cognitive symptoms.
Because Alzheimer’s disease is the most common form of dementia, most medicine for dementia was designed with the particular physiopathology of Alzheimer’s in mind. Often, testing of MCI patients shows biomarkers or physical changes to their brains and nervous systems consistent with Alzheimer’s disease, such as the presence of beta-amyloid in spinal-fluid samples. For those people, MCI is considered by many physicians to be a prodromal (pre-symptomatic) form of Alzheimer’s, with a high likelihood of progressing to true dementia. Wouldn’t it stand to reason, then, that treating such patients with proven Alzheimer’s drugs would be super-effective, since it would be a form of very early intervention?
You would think so. Yet that has not been the case. In 2004, the New England Journal of Medicine published research pitting the Alzheimer’s drug donepezil against placebo and vitamin E in a group of about 200 people with MCI who had indicators of prodromal Alzheimer’s. Although donepezil appeared to provide minor advantages at certain points here and there during the trial, by the end of three years there was effectively no difference in outcomes.
Three years later, another randomized trial, this one published in The Lancet, compared the drug rivastigmine to placebo in more than 1,000 people with MCI to see if rivastigmine could significantly extend the time it took them to progress to dementia. Not only was there no significant difference in this conversion rate, but a high frequency of adverse events led the authors to conclude that they could not recommend rivastigmine for MCI.
Similar stories have played out with the substances galantamine, ginkgo biloba, non-steroidal anti-inflammatory drugs, statins, and more. Doctors aren’t sure why some of these medications are effective for early Alzheimer’s but not for MCI. One possibility is that the mechanisms of action are targeted at brain changes that have not yet occurred at such an early stage of disease.
One of the frustrations of an MCI diagnosis is that the person is experiencing noteworthy cognitive symptoms that aren’t quite severe enough to warrant a dementia diagnosis, which would make them eligible for medication to slow the progression of the disease. For most of them, their MCI will never progress to dementia. That’s a very good thing, but it leaves them with no pharmacological option for treating their MCI. And of course, no one knows for sure whether their MCI is destined to progress to dementia or not. Some people remain in this state of limbo forever.
People diagnosed with MCI are encouraged to monitor their symptoms carefully (with the help of their loved ones) and to schedule regular check-ins with their doctors to see if their MCI is worsening. By doing so, of course, this gives them the hope of pharmacological intervention as soon as they’ve crossed the line to dementia. But this waiting game often leaves them in a psychologically taxing state of hypervigilance combined with an unsettling mixture of hope and dread surrounding a possible “someday” upgrade of their diagnosis, which would at least give them access to dementia treatments.
It absolutely makes sense to inquire about the availability of drugs to treat your MCI. New medications are always becoming available. You can also ask your doctor for information about enrolling in an ongoing clinical trial. However, while the medication could be successful, there are also downsides to all clinical trials in general that you should be aware of:
But if you feel strongly enough about seeking some form of medical treatment, these considerations might not stand in your way.
You also can ask your doctor whether he or she is comfortable prescribing a medication off-label, meaning for a purpose or diagnosis for which it has not been approved by the FDA. Doctors’ comfort levels with this practice vary, and off-label usage is sometimes stymied by the refusal of insurance companies and Medicare to pay for drugs without an FDA-approved diagnosis. Off-label use also exposes you and your physician to the possibility of unforeseen effects, since the FDA’s approval process requires evidence of safety and efficacy only in a specific patient population of which you are, by definition, not a part.
There’s still a lot people can do to maintain their cognition and slow the possible progression of MCI. These include:
Talk with your doctor about how to set and achieve these goals and others, and ask your family for support as you embark on a new lifestyle. The heartening news is that these steps have been shown repeatedly to work, with some of them proven to be just as effective as medication in people with mild dementia.
