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

Feb 20, 2019 | Dona Locke | @DrDonaLocke | Comments (17)

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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!

Interested in more newsfeed posts like this? Go to the Mild Cognitive Impairment (MCI) blog.

I cannot identify (yet) but can sympathize. I am headed in that direction, forgetting things and having a husband who is always saying ‘don’t you remember’ etc. More annoying is that he tries to prevent me driving even though I have absolutely no problem with that (yet). I have comforted myself by reading every book on the subject in the library and am confident that I will be capable of knowing when I need assistance and willing to accept it.
V.

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@emyliander

I am new to this group and am trying to figure out if I have MCI or not. A therapist said he thought I may have mild dementia, based on what I told him. My psychiatrist was upset that it had been suggested.
In the meantime I am having much trouble with my memory. In the past two weeks I have lost my pocketbook which has my debit card, and I don’t remember what else, probably some money, medication for one dose for when I forget to take it before I leave home and odds and ends. Since August I’ve lost all my health cards as well as my handicapped daughters cards, I kept them all together. I lost my drivers license, got a temporary one, received a new card and have lost that.
When driving home at night recently on a very familiar road which I travel twice a week, I got distracted and didn’t know where I was, so I just kept driving until I saw something familiar. I read an article and the next day can’t remember what I read. I have difficulty with people I know well, remembering names. Today I couldn’t remember if it was 2019 or 2020.
I get busy doing things in the house and forget to eat breakfast and lunch, then I get a low blood sugar, and have something to eat.
My husband is always saying “ don’t you remember this, “or that . And I say yes, even though I don’t, so I don’t have to listen to all the reminders and explanations. Sometimes I forget appointments, or to call someone who I said I would. I could go on for ever. Funny that I remember the things I forget, probably because they all have bad consequences, I don’t know.
Can anyone identify with this ?
Thanks, Skylark.
PS I have commented under a different email address in other groups, but had difficulty getting on this group with the same address.

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I was diagnosed with MCI at age 62 due to many of the same circumstances happening to me. I am now 65. At age 50 I had 17 months of horrific chemo and was told before each treatment that my 'chemo cocktail' showed signs of causing memory loss in those receiving it. I thought, what choice do I have as without it I would not survive. Some days are very frustrating while others are just fine. I ask, or tell, my husband the same things through out the day and he says 'you already told me that' and it frustrates me and I get up and walk out of the room. I read books and cannot remember what I read. I walk into a room and can't remember why. I have become somewhat anti-social because I don't want friends to think 'what is wrong with her'. One thing that helps me is I am very active with Zumba, walks in the forest behind my house (I know the trails so well I don't get lost), weights, and calm myself with deep breathing exercises, etc. We have made plans to move closer to our son as this process continues. What frightens me the most was watching my very vibrant mother, who was a Judge, slowly sink into that ugly disease called Alzheimers and I wonder 'will that be me'. I find if I keep a smile on my face I don't experience the frustration as much. I really enjoy all the articles I read and don't feel so much alone. Linda

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@lindaburdett @kingstonian @emyliander - I'd like to invite you to consider participating in a Mayo Clinic Connect discussion on mild cognitive impairment in the Brain & Nervous System group, https://connect.mayoclinic.org/discussion/mild-neurocognitive-disorder-due-to-multiple-etiologies.

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@lisalucier

@lindaburdett @kingstonian @emyliander - I'd like to invite you to consider participating in a Mayo Clinic Connect discussion on mild cognitive impairment in the Brain & Nervous System group, https://connect.mayoclinic.org/discussion/mild-neurocognitive-disorder-due-to-multiple-etiologies.

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Thank you Lisa for the invitation, I would like to join the above discussion group and try to figure out what is happening. I didn’t mention that I am in my early 70’s. I will now open the above link. Emy

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@lisalucier

@lindaburdett @kingstonian @emyliander - I'd like to invite you to consider participating in a Mayo Clinic Connect discussion on mild cognitive impairment in the Brain & Nervous System group, https://connect.mayoclinic.org/discussion/mild-neurocognitive-disorder-due-to-multiple-etiologies.

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Yes, I would be interested in participating in a Mayo Clinic Connect discussion group on mild cognitive impairment in the Brain & Nervous System group.

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I would be interested but I live in Kingston Ontario which might disqualify me.
Viki

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@kingstonian

I would be interested but I live in Kingston Ontario which might disqualify me.
Viki

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Hi, Viki @kingstonian - your country won't disqualify you in any way, since it's a virtual, online discussion. We have Mayo Clinic Connect members who live all over the world.

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