To Medicate or Not to Medicate in MCI; That is the Question

At one of our recent HABIT sessions, a group of our patients with MCI expressed frustration and confusion about why some of them had been prescribed a medication (such as donepezil or rivastigmine or even memantine) while others of them have not. None of the HABIT team are physicians, but we generally explain to our HABIT participants, that there currently are not any medications FDA approved for Mild Cognitive Impairment. The American Academy of Neurology (AAN) has updated its treatment guidelines to include:  “For patients diagnosed with MCI, clinicians should counsel the patients and families that there are no pharmacologic or dietary agents currently shown to have symptomatic cognitive benefit in MCI and that no medications are FDA-approved for this purpose.” (pg. 132). However, we also know that some of patients are prescribed one of these medications. The AAN guidelines note: “For patients diagnosed with MCI, clinicians may choose not to offer cholinesterase inhibitors. If clinicians choose to offer cholinesterase inhibitors, they must first discuss with patients the fact that this is an off-label prescription not currently backed by empirical evidence.” (pg. 132).

So, the professional guidelines say that no medications are approved or showed to be beneficial with empirical evidence but also leave open the possibility that clinicians may offer medication treatments to their patients with proper discussion.

Here in Arizona, I work very closely with two expert Behavioral Neurologists (a type of neurologist who specializes in the impact of neurologic disease on memory, behavior, and other aspectis of cognition). Dr. Bryan Woodruff and Dr. Rick Caselli, both of whom I've had the pleasure of working with since 2005. I sat down with them to help us understand this issue from a Neurologist’s perspective. Both of them routinely refer their patients with MCI to the HABIT program.

Dona Locke (DL): Drs. Caselli and Woodruff, first of all, we have reviewed that there is not currently any medication FDA approved for Mild Cognitive Impairment. Why is that?

Richard Caselli (RC):  Medications are generally approved for diseases, and MCI is a syndrome, that is, a set of symptoms and not a specific disease.  The medications one might consider would be those approved for Alzheimer’s disease, and if we know someone has Alzheimer’s, then it is reasonable to consider these medications.  Clinical trials in MCI patient groups have failed to show consistent benefit, so they are not recommended for MCI in general but if we have reason to believe someone’s MCI is due  specifically to Alzheimer’s disease it is reasonable to consider using them.  A patient with MCI may or may not be excited by the idea of being put on an Alzheimer’s disease medication so some may opt out even if offered.

Bryan Woodruff (BW):  It is not for lack of trying!  There actually was a large, well-designed clinical trial conducted years ago looking at the efficacy of medications like Aricept in the setting of MCI, and it was determined based on that trial that there was no clinical benefit of such medications for MCI.  This was a study lead by Dr. Ronald Petersen at Mayo Clinic in Rochester, Minnesota, and he is the clinician-scientist that spearheaded the development of the diagnostic label “MCI” based on his extensive research in the field.

DL: Then why do some of our patients end up on a medication while others do not?

RC:  Given the complexity of any syndrome whose underlying cause may not be clear, it is understandable that there will be variation in how it is handled.  And that holds true for patient preferences as well, as I mentioned above.

BW:  In my practice I usually consider a medication for MCI when I see evidence for declining cognitive performance on repeat assessment.  This might be based on my repeat office mental status examination, or on detailed neuropsychological assessment.  In particular, when I see that the cognitive difficulties are expanding beyond just memory (for example, affecting language skills or spatial reasoning), I will consider adding a medication.

DL: If a patient were prescribe a medication, what are some of the medications they might take?

RC:  There are 4 that are approved for Alzheimer’s disease, all that are intended to improve cognition and to some degree daily functioning.  Three are in the same chemical class called the acetylcholinesterase inhibitors (they are donepezil, rivastigmine, and galantamine) while one is different, memantine.  Of course if someone with MCI has other types of “mental” symptoms such as depression or anxiety then one might use medications for those types of symptoms rather than an Alzheimer’s disease drug.

BW:  For MCI that is worsening, I usually pick one of the cholinesterase inhibitors, either Aricept (donepezil), Exelon (rivastigmine), or Razadyne (galantamine).

DL: What are some of the risks of taking one of these medications?

RC:  For the cholinesterase inhibitors the most common side effects are gastrointestinal upset, so loss of appetite, nausea, vomiting, and diarrhea.  When taken close to bedtime they sometimes can cause vivid, unpleasant dreams.  Memantine has few side effects, and they tend to differ between patients.  But, the most common compliant for any of these drugs is that they do not seem to help enough.

BW:  About a 1/4 to 1/3 of patients taking these medications will experience gastrointestinal upset, usually nausea or loose bowel movements.  Taking the medication with food can help to minimize that.  Sometimes patients will experience leg cramps at night or vivid dreams, but usually we can avoid that by having patients take the medication in the morning.  We also use caution in prescribing such medications when patients have a known history of a slow heart rhythm. All of this is related to how the medications work; they boost levels of a chemical messenger in the brain called acetylcholine, which helps with the cognitive symptoms, but acetylcholine also has effects on other parts of the body including the gastrointestinal tract, muscles, and heart.

DL: Can you describe your specific approach to patients, and how you might decide in some cases to try a medication and other cases you may not?

RC:  First I try to ascertain what the underlying cause of the MCI might be.  If I think it is Alzheimer’s disease, I will discuss the option of these medications and indicate they are optional.  That is, since they have only very modest effects, and they do not prevent the problem from getting worse, there is no strong mandate for anyone to take them.  But, if a patient wants to try something to see if it helps, then we go for it as long as they are otherwise healthy enough (for example, if someone has had a major resection of much of their intestine, I will discourage an acetylcholinesterase as they would be at high risk of side effects).

BW:  If I am seeing someone with MCI back for follow-up, and there is clear evidence that they are declining on their cognitive assessments, I usually will discuss the option of a trial of a low dose of one of the cholinesterase inhibitors.  I do explain that such medications are still considered “off-label” for use in the setting of MCI, so may not be covered by insurance.  This could be cost prohibitive for some patients.  Also, I explain the potential for unwanted side effects as we talked about before.  Some patients would prefer not to take the medication with no proven benefit and potential for side effects after that discussion.  Others do want to try something, and in those situations, we proceed with a trial of the medication.

DL: Thanks so much to both of you for your time! Is there anything else you’d like our patient’s with MCI to know about living with MCI?

RC: Because Alzheimer’s disease is a common cause of MCI many people worry they will end up in a nursing home.  It is important to remember that we use the term MCI because at this early stage we are not usually certain what is the cause.  Even if we have good reason to suspect Alzheimer’s disease, the rate of progression varies greatly from person to person.  Our goal is to keep people as healthy as possible to minimize any further deterioration.  Exercise, diet, remaining socially active, getting enough rest are all things we can do to help ourselves.

BW:  I think we all are predisposed to look for a “simple fix”, but like most things in life, real solutions are rarely simple.  Hopefully some of the clinical research that is ongoing will identify more effective treatments for MCI and more serious cognitive disorders like the various forms of dementia.  We all should strive to live healthy, active lifestyles, as there is an abundance of published research that shows that staying active physically, mentally, and socially is good for our brains.  We all should also be eating healthy and getting enough sleep.

We hope this helps those of you living with Mild Cognitive Impairment and your loved ones understand that there is not always a straightforward approach to medications for MCI. There are not any FDA approved medications for your physicians to automatically recommend; however, there are often times when your physician may wish to try a medication, or may support your doing so if you wish. So, in the end, if you have questions about medications, we encourage you to raise these questions with your physician. We’d love to hear your comments or experience with medications (or without medications). In the end, we at the HABIT team will continue to do all we can to follow, and offer, all the non-medical therapies that can help with MCI and related symptoms. There are always ongoing medical therapy trials, and we’re ever hopeful of scientific breakthroughs on the medical treatment side. Until then, we’re going to continue to support you all living with Mild Cognitive Impairment!