Webinar: Medication in Dementia and Mild Cognitive Impairment
Dementia Australia webinars are free videos where subject experts discuss topics relating to dementia for a general audience.
In this webinar, Associate Professor Michael Woodward discusses medications used to treat dementia and mild cognitive impairment (MCI). Michael will explain the importance of managing medications, and recent developments in research.
Transcript
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[Title Card: Medication in Dementia and Mild Cognitive Impairment]
Assoc. Prof. Woodward: Hello, everybody. I'm associate Professor Michael Woodward, and I'm an Honorary Medical Advisor to Dementia Australia. And the topic I want to talk about is medication in both dementia and in mild cognitive impairment. Firstly, I'm currently on the land of the Wurundjeri Woi-wurrung people, traditional custodians of the land, and I pay my respect to their Elders past and present, and I extend that respect to Aboriginal and Torres Strait Islander people watching today. I have no direct conflicts of interest in the material I'm going to be presenting.
So, what I hope to do today is to talk about medications used for dementia, and for those with mild cognitive impairment. I'm going to talk particularly about medications for cognitive impairment, but also, medications used for behavioural and psychological, or so-called responsive symptoms, that are accompanying those who have dementia and mild cognitive impairment in many cases. I'm also going to talk about medications for other conditions that may be present in those with dementia and mild cognitive impairment, particularly pain and sleep. I'm going to talk about complementary and alternative medications. I'm going to talk about what we mean by polypharmacy and the dangers of this, and also, I'll finish up with some more optimistic news on future and recent treatment breakthroughs.
Now, the medications that are used specifically targeting cognition and function, or independence in those with dementia are cholinesterase inhibitors, memantine, and what we call atypical antipsychotics. I'll go into these in a bit more detail. Some of these medications are also used in those with mild cognitive impairment. And the reason that we have these medications is because of research, some of which was done over 20 years ago. For instance, one of the most commonly used medication targeting cognition and function in those with early stages of dementia due to Alzheimer's disease, is a drug called donepezil. And it's got a number of trade names such as Aricept and Arizil, and this is the study that looked at it for over a year. Basically, in purple, we've got the people treated with the drug, and in yellow, we've got people treated with placebo. And the scale that we're using is the CDR, or clinical dementia rating scale. And the main thing to note here is that those who are on donepezil declined very little over the 52 weeks, whereas those who are on placebo declined considerably, so that by the end of the study, there was a statistically significant difference between those treated with the active drug and those on placebo.
We have similar results for other drugs that are used for cognition in those with particularly the early stages of Alzheimer's disease, causing dementia. This is one called Rivastigmine, and its trade name is Exelon, and it's mainly now given as a patch, a five and then a 10 square centimetre patch. And again, you'll see that this is a scale where it goes in the opposite direction to the last slide. In other words, the higher the line the better, and the placebo group didn't change very much. This is on the MMSE, one of the scales we use to assess memory, whereas those treated with the Exelon patch, or in an older form, a capsule, with the same amount of medication did considerably better than placebo. This is a 24-week study, and there's also similar results for galantamine, which is the third of the drugs used for cognition and function in those with the early stages of dementia due to Alzheimer's disease.
Now, we also find that people who have mild cognitive impairment, but more so people who have dementia due to any condition including Alzheimer's disease, suffer from what we call responsive symptoms, or previously, we might call them behavioural and psychological symptoms. And the drugs that we use for these include antipsychotics. These are used for delusions, paranoia, and hallucinations, but they can also be effective in those with agitation and aggressive behaviour. There's a number of medications in the category of anti-psychotics, and these include Risperidone, which has the greatest amount of evidence supporting its use, but also other drugs such as Quetiapine, and sometimes, we use Olanzapine. These have various trade names.
We can also treat depression in those with mild cognitive impairment and dementia. The antidepressants have been widely used in the general population. The evidence that they work in those with mild cognitive impairment and dementia is not quite as strong, and in fact, a number of trials have shown very little efficacy, but they still might've been beneficial for some people, and they are still tried when there is significant depression present. Some of the very new drugs that have been particularly trialled in those with Alzheimer's disease or dementia might be more effective. One is called Duloxetine. Sometimes, a class of drugs that we call Benzodiazepines are used to treat anxiety associated with Alzheimer's, and mild cognitive impairment, but they're not recommended for long-term use. They can be used as occasional doses.
Now, remember, with respect to medications, we shouldn't rely entirely on them. We should combine them with non-pharmacological approaches in the case of these responsive behaviours. So, sometimes, the way to treat a responsive behaviour is to change the environment, or to provide some other activity or stimulation, rather than just reading for the prescription pad. If we do use these medications, they should be used short term. The government recommends we use them for only 12 weeks, but they are sometimes used for longer periods, and we should aim for the lowest effective dose, and indeed, we should try to reduce the dose wherever possible. So, it might be worth having a chat to your doctor if one of these drugs has been considered or has been commenced, to see if it can be stopped or if the dose can be reduced.
Now, we also use medications for pain. I'm picking up on this because pain is often under-recognised and under-treated in those who have cognitive impairment. It can reduce the quality of life, and it can actually contribute to some of these responsive behaviours. We start with simple analgesia such as regular paracetamol, some of the stronger drugs such as what we call opioids can be very effective, but there's a risk of adverse effects. For example, sedation, falls, and worsening of cognition. Again, we should always consider reducing or stopping these drugs altogether, particularly the stronger drugs.
Sleep is often affected by cognitive disorders. It's very commonly affected in those without cognitive disorders. And the way we tackle this is to try what we call good sleep hygiene. For instance, avoiding caffeinated beverages later in the day, making sure you get enough exercise during the day, but not the last thing at night, making sure the room is sufficiently quiet and the lighting is sufficiently subdued. That can be difficult sometimes in residential care. If you do need medication, melatonin, there's a number of trade names, but the controlled release one called Circadin is a good one to try. These can be used. They're particularly helpful in inducing sleep, but not necessarily in maintaining sleep.
Again, we try to avoid the benzodiazepine class of drugs for sleep wherever possible, and there's another group of drugs we call the Z drugs, because their chemical name starts with the Z, but they work in a very similar way to drugs like Temazepam and Nitrazepam. There are many other drugs that have sedative effects, but they're not indicated for poor sleep because their side effects are too significant. One exception, however, might be the use of the antipsychotics that I mentioned earlier on for responsive behaviours. Well, they can also be used for those who have a particular form of sleep disturbance called REM sleep behaviour disturbance. That's where we act out our dreams, we're not paralysed, and our arms and legs move around as we are dreaming. It's particularly associated with one form of cognitive impairment called Lewy body disease.
One of the reasons that we avoid these drugs is because of the effect that they can have on our mobility. They can contribute to falls, they can make us overly sedate, and they can worsen our cognition. And if they are needed, we tend to, as with the antipsychotics, try and use them short-term only, and we always aim to de-prescribe or to cease them. Now, complementary, and alternative medications are frequently used by older people and including those with cognitive impairment, and sometimes, they're not recognised as a medication. “Doctor, I just take the tablets you give me, but by the way, I take seven or eight other things that I get from the health food shop, or online, increasingly. They can cause adverse effects just because they're not, if you like traditional medicines, doesn't mean that they're safe. And they can also interact with medical conditions with other medications. So, we need to make sure our doctor is aware of the things that we're putting in our mouth, not just the ones that the doctor has prescribed.
Unfortunately, there's very little or no evidence that these complementary medications are effective, and this includes ginkgo, ginseng, brain foods of various types. There is evidence, however, for one substance that we might not think of as a medication. This is a drink called Souvenaid, and it's been shown in quite a considerably long study, three years now, to be effective in those with the milder stages of Alzheimer's disease, causing mild cognitive impairment or the early stages of dementia. So, I, as a doctor, always recommend Souvenaid, where Alzheimer's disease is in the early stages.
A term that you might hear about is polypharmacy, and that means many medications. There's no standard definition, and it's not just the number of medications, and it does include over the counter and complementary medications. Some of the common definitions include six or more medications, or particularly, if there's one potentially inappropriate medication – a medication where the risk from the medication is very high compared to its potential benefits. You can also describe polypharmacy as being prescribed medications which are not appropriate for our diagnosis, or where the disease has resolved, but the medication is being continued for whatever reason, or we're simply using more medications than are needed. So, polypharmacy is a big problem. And the risk factors, the reasons that some people are subjected to polypharmacy have been shown in research to include being older, having complex and multiple diseases. Yes, you might need medications for these, but there's a risk that you'll be put too many medications.
Interestingly, polypharmacy seems to be associated with people in lower socioeconomic classes, which is surprising because these medications may be quite expensive. It's more common when there's difficulty accessing healthcare, in other words, accessing a doctor who is trained to de-prescribe, or where there's limited understanding about appropriate health decisions, it's also more common in people who have just come out of hospital where medications should have potentially been stopped, or at least there'd be a plan to cease the medications.
The dangers of polypharmacy include falling over, becoming acutely confused, what we call delirium, on top of our more chronic memory problems. These combinations of drugs, this polypharmacy, can also contribute to incontinence, to decline in our function, what we call frailty or fragility. It can also mean that our drugs are more likely to interact with each other, and this can cause adverse drug effects. It can even lead to hospitalisation and even to death. Also, if we're being subjected to polypharmacy, it's hard to make sure we take our medications correctly. We might be on one that's taken three times a day, another one that's taken once a day, another one that's taken before meals, and so on. It's very hard to follow a complicated regime like that. The simplest thing is to be on less medications.
Sometimes. it makes the medications too expensive and people can make bad decisions about, “Well, look, I'll take this tablet today, and tomorrow, I'll take this tablet,” and it can also cause general medication wastage. I ask you to look in your medicine cabinet where I'm sure you'll see some medicines that are well out of date, and may not have ever been needed.
So, in conclusion so far, I'd like to say that the medications we've had to treat cognitive impairment and they've been around for over 20 years, do have a limited role. They can help with memory. We also have medications for responsive or challenging behaviours, and we can also have medications that can treat the loss of function that goes along with our cognitive impairment. People with such problems with cognition, people with dementia and mild cognitive impairment, however, should not be denied treatment where it's needed, and this includes treatment of depression, pain, and poor sleep. As I've said, polypharmacy is all too common and we should always aim to de-prescribe and be sure that the medication that's being started is indicated. You should have this discussion with your doctor, “Do I really need this doctor? Or does my husband, or wife, or my mother, or whatever, really need this medication? That's a very reasonable question to ask.
Now, it's not all bad news with respect to medication. We may already be on the breakthrough stage with respect to medications to treat the underlying cause of cognitive impairment, particularly where that's Alzheimer's disease. This new era has begun. I think we're now at actually what I would call “the end of the beginning” in developing effective drugs for dementia, and in particular, for Alzheimer's disease. And this is the result of very extensive research.
If we look at this circle on the left-hand side here, there's actually 141 different symbols, and these are unique drugs that have been trialled for the treatment of all forms of cognitive impairment, but particularly, Alzheimer's disease. And they're in various stages what we call phase one, two, and three trials. And some of them are disease modifying biological drugs. Some of them are cognitive enhancers. Some are tackling the responsive behaviours we spoke about before, and some of these are just small tablets that you take, or small molecules that you can take in tablet form, and not drugs that need complicated administration such as intravenous, or injections under the skin.
About 78% of all these new treatments are potentially modifying the underlying disease process, and some of them are repurposed agents that have been tried in other conditions. 11% of these drugs are for the responsive behaviours, and most of these are moving into phase three trials, which is the most advanced stage of research.
Here's an example of one drug which has come through this process. This is called Aducanumab, and there are two different studies that have shown that it does exactly what it was aimed to do, which is to remove amyloid, to remove the amyloid plaque that's present in the brain of people with Alzheimer's, and that is associated with the disease itself. So, in these two studies, we see that by week 78, the red line is the people on placebo. There's no reduction in amyloid, but the blue and green lines show very significant reduction in amyloid in those on either lower or higher doses of Aducanumab.
Another drug is called Lecanemab, and here, we're looking not at a reduction in amyloid, but we're looking at a scale that measures the amount of cognitive and functional impairment. And essentially, the green line is those on the drug, and they are deteriorating less rapidly than those on placebo, which is the black line here. These results were presented at a meeting called CTAD at the end of last year, and show basically a 27% slower rate of decline in those treated with Lecanemab compared to those on placebo. Again, this is through removing or leaching out the amyloid plaque. In fact, now, three drugs in this class have been approved or about to be approved. These are Lecanemab, Aducanumab, and Donanemab. The phase three results of Donanemab were presented just last month. I'm recording this at the end of July. Well, actually, they were presented just two weeks ago, in Amsterdam, in the middle of July.
There's another monoclonal antibody that's removing amyloid called Remternetug, and this trial is going to give results in 2024.
Another one, Trontinemab is being trialled in phase two studies, or phase one studies now, but they'll be moving to phase two in the very near future. And there's a number of other drugs you can see, they've just got a series of numbers and letters to describe them at this stage, and they're only in early stages of research. But I believe that we are now at the stage where we're truly modifying Alzheimer's disease, not just treating the symptoms of it, and will soon, I also hope, have drugs for other forms of cognitive impairment such as Lewy body disease or frontotemporal dementia. So, that's all I wanted to say today. Thank you very much for listening, and if there's any questions, please speak to your local Dementia Australia resource, and if necessary, they can contact me for some more information. Thank you for listening.
[Title card: Dementia Australia. 1800 100 500. Dementia.org.au]
[Title card: Together we can reshape the impact of dementia]
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More on medication, dementia and mild cognitive impairment
- Treatment and management of dementia
Dementia is an umbrella term for a variety of conditions. As a result, there are many pharmacological treatment, non-pharmacological treatment and management options.
https://www.dementia.org.au/professionals/treatment-and-management-dementia - Mild cognitive impairment (MCI)
Mild cognitive impairment (MCI) is a brain condition that affects memory and thinking more than normal aging, but not as severely as dementia.
https://www.dementia.org.au/brain-health/mild-cognitive-impairment-mci
The National Dementia Helpline
Free and confidential, the National Dementia Helpline, 1800 100 500, provides expert information, advice and support, 24 hours a day, seven days a week, 365 days a year. No issue too big, no question too small.