An estimated 50 million people worldwide are living with dementia.1 The most common type of dementia is Alzheimer’s disease (AD), accounting for about 60%–70% of dementia cases,1 followed by vascular dementia (VaD) with a prevalence of about 20%.2 Other types of dementia include dementia with Lewy bodies (DLB), Parkinson disease (PD) dementia, and frontotemporal dementia (FTD).3 Along with cognitive decline, 90% of patients with dementia experience behavioral and psychological symptoms of dementia, such as psychosis, aggression, agitation, and depression.4 Dementia-related psychosis (DRP), which includes delusions and hallucinations, contributes to institutionalization, cognitive decline, and caregiver burden.5

In this Academic Highlights, Drs Ballard and Aarsland will address best practices for improving outcomes for people living with DRP and their care partners.

Overview of Dementia-Related Psychosis

A review6 of 55 studies showed that psychosis occurred in about 40% of patients with AD; delusions occurred more frequently (36%) than hallucinations (18%). Recurrent visual hallucinations are a core feature of DLB7 and are a common characteristic of PD dementia.8 Simple hallucinations are rare, with most patients experiencing complex hallucinations daily. The experiences often feature people or animals.8,9

Dr Aarsland stated that delusions and hallucinations may increase in frequency over time and be persistent in some individuals.10,11 According to a study12 of 83 patients with dementia and at least 1 psychotic symptom, most patients experienced psychotic symptoms at a frequency between daily and weekly. Thirty-seven patients (45%) were mildly distressed by their psychotic symptoms, and 14 (17%) were severely distressed.12

A complex interplay of factors can contribute to delusions and hallucinations in people with dementia (Figure 1).13–16

Figure 1. Factors Contributing to Psychotic Symptoms in Patients With Dementia

According to Dr Aarsland, clinicians must probe factors that contribute to DRP in discussions with the patient (if possible) and the care partner. When talking to patients and carers, it is important to always explore both whether apparent delusions might in fact be true and whether there are factors before or after the occurrence that might initiate or maintain the behaviors. Based on Dr Aarsland’s clinical experience, it is usually not helpful for clinicians or carers to argue with patients or try to convince them that these thoughts or sensory impressions are not real; it is more helpful to try to understand and acknowledge the patient’s emotional reaction.

Impact of Dementia-Related Psychosis on Patients and Caregivers

Delusions and hallucinations may directly impact the patient’s ability to perform cognitive and functional tasks,17 which can contribute to carer distress.18,19 Further adding to carer distress, Dr Aarsland explained, patients experiencing hallucinations, such as seeing a person in the house who should not be there, may run after “the person” or even call the police for help.

Additionally, although some psychotic symptoms might not be dramatic, they are often accompanied by troublesome affective and behavioral symptoms that can be stressful for the carer. For instance, sleep disturbances associated with psychotic symptoms may not only lead to increased agitation and reduced daytime functioning in patients, which are challenging for carers to address, but also may cause lack of sleep for carers.20 Psychotic symptoms can also adversely impact the emotional connection between the care partner and the patient.21

Family Perspectives

Here, a relative describes her ongoing stress:

“My mother was diagnosed with vascular dementia almost 2 years ago… She is very bitter towards me since she blames me for losing her independence. I’m her power of attorney and she barely understands what that is and thinks I just go shopping with her money. She is always asking about her money and where it is. She also wants to know how much there is. She has financial scammers that are still in regular contact with her. She tells them everything. I even found out that [a scammer] tried getting in a lawyer to see her to do a new will. The only reason they didn’t succeed is because of COVID. I’m in a constant state of panic and it’s affecting my health.”22

Dr Aarsland recommended several scales to measure the impact of DRP on care partners, including the Zarit Burden Interview,23 the Relatives’ Stress Scale (RSS),24 and the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D).25 Cognitive-behavioral therapy26,27 or emotion-based and problem-focused interventions26 may help care partners cope with DRP.

Although psychotic symptoms can have an immense negative impact on carers,28,29 the symptoms do not necessarily cause distress to patients.12 Patients’ degree of insight appears to affect whether they consider hallucinations to be threatening.30 One study31 found that 40% of delusions did not cause discomfort to the patients. Dr Ballard said that discussing this perspective with caregivers may help to relieve some of their own distress.

Another point that may help care partners is that psychotic symptoms are not persistent in every patient32–34; they can last for less than 3 months.35

Dr Ballard explained that he has found it important to talk with patients and caregivers about the impact of DRP on well-being, their level of distress (and patients’ insight), the potential course of DRP, and the potential risks of medications used to treat DRP. Then, it is possible for people to knowledgeably discuss treatment options.

Terminology is important when discussing DRP with patients and caregivers. Dr Ballard noted that the lay understanding of psychosis is usually associated with schizophrenia. Individuals may be more comfortable if providers avoid terms such as psychotic and instead describe symptoms according to their presentations.

Evidence-Based Treatment

Dr Ballard explained that pharmacologic treatment is probably not necessary if symptoms are not severe and are not causing aggressive behavior that puts the patient and others in danger.36–38 Although atypical antipsychotics may play a limited role in the short-term management of psychosis in patients with dementia,39,40 any benefit has to be balanced against the risk of significant harms (Figure 241,42).38 Dr Ballard noted that the US Food and Drug Administration (FDA) requires a “black box” warning43 on atypical antipsychotic labels indicating an increased risk of mortality, other known harms, and limited efficacy in patients with dementia,4 and European agencies have similar warnings.44 Cholinesterase inhibitors may provide a pharmacologic treatment alternative for psychosis in people with DLB,45 but benefits are less clear in people with other dementias.

Figure 2. Potential Serious Adverse Effects With Atypical Antipsychotics in Patients With Dementia

Guidance on Atypical Antipsychotics in DRP

According to the American Psychiatric Association (APA) practice guideline46 on the use of antipsychotics for agitation or psychosis in individuals with dementia, antipsychotic medication should be used only when symptoms are severe, are dangerous, and/or cause significant distress to the patient. The APA recommends that, before nonemergency treatment with an antipsychotic is initiated, the potential risks and benefits must be assessed by the clinician and discussed with the patient (if feasible), family, and/or the surrogate decision maker. If the risk-benefit assessment favors the use of an antipsychotic, the treatment should be initiated at a low dose and titrated up to the minimum effective dose as tolerated.41,46 (The first-generation antipsychotic haloperidol should not be used in the absence of delirium.) Response should be assessed with a quantitative measure. Dr Ballard recommended the Neuropsychiatric Inventory (NPI)47–49 for assessment and monitoring.

If no response is evident after 4 weeks, the medication should be tapered and withdrawn.46 Among those who respond adequately, an attempt to taper and withdraw the medication should be made within 16 weeks unless previous attempts at tapering were associated with recurrence of symptoms. A long-acting injectable antipsychotic agent should not be used.

Dr Ballard explained that since the 2016 publication of the APA guidelines,46 evidence has become available on pimavanserin, a selective 5-HT2A inverse agonist, which is FDA-approved for the treatment of hallucinations and delusions associated with PD.50 A meta-analysis by Zhang et al51 concluded that pimavanserin is effective in the treatment of PD psychosis. Unlike other atypical antipsychotics, pimavanserin has no clinically significant antagonism of dopaminergic, muscarinic, or histaminergic receptors.52 Evidence53 indicates that pimavanserin may decrease hallucinations and delusions in patients with AD, PD dementia, VaD, DLB, and FTD (including among nursing home residents with severe psychotic symptoms54), but it is not FDA-approved for this indication.

Dr Ballard summarized that a patient treated with an antipsychotic for DRP may have marginal benefits in the context of many potential harms; however, for patients with severe symptoms, the risks may be worthwhile with short-term treatment. Atypical antipsychotics are not a widespread, long-term treatment solution.5

Family Perspective

Here, a family member describes the struggle to find therapy for a patient with PD-related psychosis:

“My father-in-law is very sensitive to certain medications. [One antipsychotic] made him hallucinate more. . . . He goes through phases. He’s generally happy, then has a few days of constant hallucinations and gets aggressive when the sun goes down.”56