During the 2024 Alzheimer Association International Conference (AAIC), Pharmacy Times interviewed Clive Ballard, MD, PhD, professor of age-related diseases at the University of Exeter, UK, who discusses the prevalence of psychosis in Alzheimer disease (AD). The mental disorder can lead to rapid cognitive and functional decline, and the best course of action for treating symptoms involve non-pharmacological interventions. Ballard also discusses the plenary session he hosted during AAIC and emphasizes his optimism for the continued research and development of treatments.
Key Takeaways
- Prevalence and Impact of Psychosis in Alzheimer Disease: Psychosis affects about half of people with Alzheimer disease (AD) and is associated with a more rapid decline in cognitive and functional abilities, reduced quality of life, damaging relationships between patients and caregivers, as well as a higher likelihood of institutionalization.
- Distinguishing Psychosis in AD from Other Conditions: Psychotic symptoms in AD typically present as simple delusions or visual hallucinations, which differ from the more complex symptoms seen in earlier-life psychotic disorders. Ballard notes that it is important to differentiate these from delirium, which can occur suddenly due to acute medical conditions.
- Treatment Approaches and the Role of Pharmacists: Non-pharmacological treatments are recommended as the first line of intervention for psychosis in AD. While antipsychotic medications may be necessary for severe cases, they should be used only when necessary, because of the associated significant adverse effects (AEs). Pharmacists play a vital role in monitoring medication regimens to minimize harmful drug interactions and AEs.
Pharmacy Times: Can you introduce yourself?
Clive Ballard: I'm Clive Ballard, professor of age-related diseases at the University of Exeter in the UK.
Pharmacy Times: How might the presence of psychosis affect the progression or prognosis of AD, and how might it manifest in different stages of AD?
Ballard: Psychosis is very common in people with Alzheimer disease (AD). Over the course of the illness, about half of people with AD will develop psychosis, and it has a big impact. It affects people's quality of life, their likelihood of being institutionalized in a nursing home, but also people who have psychosis, they tend to decline more quickly in terms of their function and cognitive abilities. So, these are very impactful symptoms.
AD is a tragic condition for many people. And for most people, it's a progressive condition that leads to decline in function and ability, and eventually to loss of independence. But I think for people who have psychosis [what] is particularly challenging, that decline tends to be more rapid, but the symptoms also impact people's quality of life, they impact people's relationships with their caregivers and others, so it tends to kind of isolate people as well as accelerating the course of their illness.
Pharmacy Times: What is the long-term prognosis for patients with AD who develop psychosis? Does it differ than someone who might have AD alone?
Ballard: Psychosis is generally more common early in life. Conditions like schizophrenia and bipolar disorder, for example, commonly have psychotic features. The features that you see in people with AD tend to be very different. They tend to be very, very simple kind of suspicious ideas, [for example,] somebody's stolen my wallet, somebody's stolen my purse, and the hallucinations tend to usually be visuals of people seeing [other] people or sometimes animals in the corner of a room, for example. So, the symptoms are very different to the types of symptoms that you experience in sort of earlier life psychosis.
The one important sort of diagnostic element that's important to consider is that psychotic symptoms can often happen in older people when they have delirium, and delirium is a kind of confusional state that comes on when people sometimes have infections or fevers, and as part of that, people can have some of these types of psychotic symptoms. And particularly, if symptoms have come on very quickly, at a time when somebody's more confused it's always very important to check whether there's an underlying infection, or something else that could be treatable, and whether this is in fact a delirium.
Pharmacy Times: Are there any distinguishing features or symptoms when psychosis is present in people with AD (compared with people without AD)? Are there methods to differentiate psychosis related to AD psychosis related to other factors?
Ballard: Well, I think in terms of separating psychosis, and AD from delirium, a lot of it is the speed of the onset of those symptoms, and that you often get quite an abrupt change in the level of somebody's confusion. And that often kind of fluctuates quite a lot over a period of minutes and hours, whereas although kind of the psychosis experience in people with AD, does kind of tend to relapse, and then improve. And this recurrent cycle that's over a pattern of weeks rather than over a pattern of hours and days.
Pharmacy Times: As far as treatment methods, what options are currently available and what are risks and benefits associated with their use in the AD population?
Ballard: Best practice guidelines suggest that we should be using non-pharmacological treatments as the first line of intervention. I think one of the things that's really important to remember is sensory impairments, hearing impairments, and visual impairments [all] significantly increase the risk of psychosis in people with AD. It's a simple thing, but an important thing to check and to treat.
I think other kind of simple non-pharmacological interventions like promoting enjoyable activities and social interaction. They don't so much help the core symptoms of psychosis, but some of the other things that often go along with it, like people being low in mood, irritable, agitated, those things tend to improve and you can improve people's quality of life with those types of interventions.
For people with more severe symptoms where they're really causing severe distress to people or causing risk to the person or others, I think we do have pharmacological treatments available. The most commonly used treatments are a class of drugs called atypical antipsychotics, and they do have a modest benefit in treating these symptoms, but the problem is that these drugs have a lot of [adverse effects (AEs)]. They increase the risk of death, they increase the risk of stroke, they increase the risk of falls and fractures, and they accelerate the rate of decline of the illness. So although in occasional individuals where the symptoms are severe, those treatments may be appropriate, we have to be really careful not to overuse those treatments and to discontinue them as soon as that's possible.
Pharmacy Times: How do pharmacists collaborate with other healthcare professionals, (eg, neurologists, psychiatrists, primary care physicians) in the care of patients with AD and psychosis?
Ballard: I think pharmacists can play a really important role, it varies a little bit in some health systems. For example, pharmacists have a very regular role in monitoring medications, and in some UK settings, that's been very, very successful. They will often review sedative medications like antipsychotics and encourage people to discontinue those according to best practice guidelines if they've been prescribed for too long, but also, one of the things that's a massive challenge in older individuals who develop AD [and] who often have other comorbid health conditions is that they're often on a large number of medications. And sometimes those medications can have AEs or interactions. One of the common challenges is not realized is the so-called anticholinergic burden, one of the AEs of a lot of medications at a small level. But when you combine that across a number of drugs, that can actually affect people's level of cognition, and it can also affect psychosis.
So again, the pharmacists can provide a really important service in helping doctors to review that and to try and make sure that the medications we're giving people aren't doing harm.
Pharmacy Times: What research and clinical findings will be discussed during the AAI Conference plenary session?
Ballard: At the plenary session, I tried to set out what the symptoms are, how [patients are] experiencing the impact of these symptoms, and then go through kind of what the current and future treatment options are, the sort of non-pharmacological and current pharmacological treatments, the challenges of that and how we need to be very careful when it's appropriate to use those treatments, but also to look at what we're beginning to understand about the biology and the genetic risk for these types of symptoms, and how that's leading us to new treatments and clinical trials, and sort of new targets that will become the treatments of the future.
And I think one of the things that I'm kind of excited...there's been a huge unmet treatment need for a long, long time, where we don't really have drugs that are safe enough to treat these symptoms. And I think some of the emerging therapies...there's a very good chance in the next 2 or 3 years that we'll have much better treatment options that will be safer and more effective. And I think for the first time really over the last year or so, I feel incredibly optimistic that things will be a lot better for people who have these symptoms in the future.
