Fatima is a 78-year-old lady who happens to be a retired head nurse of the local hospital. She is very well put together and vivacious when seen in the Primary Care Memory Clinic. But it's clear that she has some difficulties with memory. And her husband Mo, who accompanies Fatima to the appointment, reports that this has been happening in a slow and gradual way over the last couple of years.
In the last six months, Mo has had to take over the banking and now needs to supervise many of the everyday recipes that used to come so easy to her. Fatima takes Metformin for her Type 2 Diabetes, Sertraline for mood and anxiety and Ramipril for high blood pressure, but she’s otherwise healthy and goes swimming twice a week at the YMCA. At the clinic, Fatima participates in cognitive screening with the Montreal Cognitive Assessment or MoCA, and her score is below what was what would be normal (she scored 20 out of 30 with zero out of five on a short-term recall list of words. A normal score is 26 or higher). The physical exam is unremarkable and labs, including a CT scan of the brain, was unremarkable.
Fatima is given a diagnosis of dementia or major neurocognitive disorder. The most likely cause is Alzheimer's disease. Fatima and her family are referred to the Alzheimer society and advised to continue with her blood pressure medications and exercise program. But they have a lot of questions about medications that could help with the dementia.
In this article we'll talk about the cognitive enhancers that we currently use for dementia, what you could expect when started on these medications, and when they should be stopped.
Some facts about cholinesterase inhibitors:
- On average, patients will score 1 -2 points higher on a cognitive screening test (like the MMSE) after starting the medication.
- About 25% of those who take a cholinesterase inhibitor will have an adverse event (like a side effect or other negative outcome)
- About 5-10% of patients who have been prescribed a cholinesterase inhibitor will stop it within a year.
- These medications are not used to treat Mild Cognitive Impairment and don’t prevent or delay the onset of Alzheimer’s disease.
What are the Cognitive Enhancers?
The medications that we use most often fall into two categories: cholinesterase inhibitors and NMDA antagonists. Let's look at these medications.
CHOLINESTERASE INHIBTORS - DONEPEZIL, GALANTHAMINE and RIVASTIGMINE:
What they’re used for:
- Alzheimer's, Dementia with Lewy bodies, Parkinson's related dementia and some other dementia types.
How they work:
- inhibit the break down of acetylcholine, a chemical which is deficient in Alzheimer’s.
- Nausea, diarrhea, loss of appetite, runny nose. Some people complain of more difficulties with bladder continence, or a runny nose.
Who can’t take it:
- Those with an allergy to the medication. We use caution in those with a heart block (without a pacemaker), active bleeding from the gastrointestinal tract, wheezing, weight loss, seizures, or an unreliable medication delivery system
What to expect: *For my more scientific review of the data behind the cognitive enhancers, check out this article and video*
- This is a little bit harder to describe, but I’ll mention what we know from the scientific data and share my personal impression below. *For my more scientific review of the data behind the cognitive enhancers, check out this article and video*
- A meta-analysis (basically a compilation and analysis) of all of the randomized, controlled trials of the cholinesterase inhibitors compared those who had taken the medication to those who had taken a placebo. Overall, the treatment groups were more likely to score about 2 points higher on a common cognitive test, the Mini Mental Status Examination, and were more likely to be slightly better on a 7-point scale (called the Clinician’s Interview Based Impression of Change or CIBIC). These are fairly modest, but statistically significant differences between the two groups.
- In my experience of using these mediations with individuals living with dementia, I find that about 1 in 10 have a noticeable and big improvement, 1 in 3 have some noticeable improvement, 1 in 3 don’t change very much at all, and 1 in 3 seem to continue to worsen at a similar rate to before they were placed on the medication.
- In addition, in my experience, about 20% of individuals stop the medication related to a side effect or other issue (in clinical trials, the rate of discontinuation was around 5-10%.
- The response to the medication may also depend on the type of dementia. For those living with Dementia with Lewy Bodies, cholinesterase inhibitors seem to help with some of the hallucination symptoms, for example.
When to Consider Stopping:
- Worsening dementia
- No noticeable benefit
- Severe or advanced dementia stage
- Intolerable side effects
- The person can’t reliably adhere to the medication routine
Many patients and families ask me about stopping the medication when a person with dementia is admitted into a long-term care home. It used to be fairly common practice for us to stop these medications at the time that a person was transitioning into long-term care, but more recently, my practice is to continue, as long as none of the above conditions are met. In fact, there’s some evidence that stopping the cholinesterase inhibitor when a person with dementia in long-term care is having symptoms of hallucinations or delusions may make those symptoms worse.
Stopping a medication that was often started with great hope that it would keep a person well for as long as possible is difficult. I usually remind families that the treatment od dementia doesn’t just involve pills, but also exercise, diet, socializing, maintaining a routine and a comfortable environment are just as vital as mediation, if not more.
NMDA ANTAGONIST – MEMANTINE
What it's used for:
Alzheimer's, Dementia with Lewy bodies, Parkinson's related dementia and some other dementia types. It can be used on its own if a person can't take a cholinesterase inhibitor, or can be taken in addition to one.
How it Works:
- Memantine is a partial blocker of the N-Methyl-D-Aspartate (NMDA receptor), which reduces levels of a chemical called glutamate. Excess levels of glutamate are thought to be neurotoxic.
- Can cause blood pressure to go up or down, some stomach upset. Usually side effects are mild.
Who can’t take it:
Those with an allergy to the medication. We use caution in those with a history of seizures, or an unreliable medication delivery system
- A meta-analysis (basically a compilation and analysis) of all of the randomized, controlled trials of memantine showed that it had a mild effect on overall cognitive and functional performance. An interesting study looked at individuals who had already been on donepezil (a cholinesterase inhibitor). They then had memantine added on, or swapped for the CI. The results showed that adding memantine didn't make that much difference, but that stopping the donepezil made patients a little worse. I generally tell my patients and families that the medication is about as effective as the CI's. but doesn't seem to be better.
When to Consider Stopping:
- It's reasonable to consider stopping memantine after trying it for at least 3 months, in the same circumstances as I listed above. In my experience, many patients and families have to pay out of pocket for memantine (it's not covered on many provincial drug formularies) so it can be a big expense (about 75-150 $CAD per month). this can often be a factor in deciding if the money for the mediation is worth it, or could be better spent on another aspect of the person's care.
- Cognitive Enhancers are prescription medications that are used in some types of dementia, including Alzheimer's and Dementia with Lewy Bodies
- They aren't used in normal aging or Mild Cognitive Impairment and don't prevent dementia.
- Whether Cholinesterase Inhibitors or memantine, these medications are generally of modest benefit and are rarely "game-changers" for those living with dementia
- It's reasonable to try the medications, and to consider stopping them if they don't appear to be working, or if the person's condition or living situation changes
To learn more about Dementia, check out these articles:
Here are some of the scientific studies I mentioned in the article:
Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial: secondary and post-hoc analyses Lancet Neurol. 2015 Dec;14(12):1171-81. doi: 10.1016/S1474-4422(15)00258-6 Authors :: Robert Howard, et.al.
Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2018 Jun 18;6(6):CD001190. doi: 10.1002/14651858.CD001190.pub3. Authors: Jacqueline S Birks , Richard J Harvey.
As always, please leave a comment below if you have any questions or a story you'd like to share.