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Abstract

Along with cognitive decline, 90% of patients with dementia experience behavioral and psychological symptoms, such as psychosis, aggression, agitation, and depression. Dementia-related psychosis (DRP), which includes delusions and hallucinations, contributes to institutionalization, cognitive decline, and caregiver burden. Delusions and hallucinations tend to increase with the duration and severity of the disease, but there are also individual fluctuations. While a variety of symptoms can occur in all types of dementia, visual hallucinations are particularly common in the Lewy body dementias (dementia with Lewy bodies and Parkinson disease dementia). Mechanisms behind DRP are multifactorial, including different neurobiological factors as well as environmental, social, and psychological factors. This report examines the frequency, symptoms, and pathophysiology of DRP and communication about psychotic symptoms with patients with dementia (if possible) and their care partners.

J Clin Psychiatry 2020;81(5):AD19038BR1C

Read the related Academic Highlights

This CME activity is expired. For more CME activities, visit cme.psychiatrist.com.
Find more articles on this and other psychiatry and CNS topics:
The Journal of Clinical Psychiatry
The Primary Care Companion for CNS Disorders

Abstract

Along with cognitive decline, 90% of patients with dementia experience behavioral and psychological symptoms, such as psychosis, aggression, agitation, and depression. Dementia-related psychosis (DRP), which includes delusions and hallucinations, contributes to institutionalization, cognitive decline, and caregiver burden. Delusions and hallucinations tend to increase with the duration and severity of the disease, but there are also individual fluctuations. While a variety of symptoms can occur in all types of dementia, visual hallucinations are particularly common in the Lewy body dementias (dementia with Lewy bodies and Parkinson disease dementia). Mechanisms behind DRP are multifactorial, including different neurobiological factors as well as environmental, social, and psychological factors. This report examines the frequency, symptoms, and pathophysiology of DRP and communication about psychotic symptoms with patients with dementia (if possible) and their care partners.

J Clin Psychiatry 2020;81(5):AD19038BR1C

Read the related Academic Highlights


CME Background information

From the SeriesDementia-Related Psychosis: Recognition and Treatment
To cite: Aarsland D. Epidemiology and pathophysiology of dementia-related psychosis. J Clin Psychiatry. 2020;81(5):AD19038BR1C.
To share: https://doi.org/10.4088/JCP.AD19038BR1C
© Copyright 2020 Physicians Postgraduate Press, Inc.

Target Audience

  • Neurologists
  • Psychiatrists
  • Nurse practitioners
  • Physician assistants

Support Statement

Supported by an educational grant from ACADIA Pharmaceuticals Inc.

Learning Objective

After completing this educational activity, you should be able to:

  • Talk with patients with dementia (if possible) and their caregivers about psychotic symptoms

Release, Review, and Expiration Dates

This brief report activity was published in September 2020 and is eligible for AMA PRA Category 1 Credit™ through September 30, 2022. The latest review of this material was August 2020.

Statement of Need and Purpose

Hallucinations and delusions are key behaviors contributing to behavioral crises in patients with dementia, and a lack of consistency in assessment of behaviors has been found. Clinicians may lack awareness of the incidence of psychotic symptoms in different forms of dementia, as dementia pathology has been incorrectly diagnosed on the basis of the presence or absence of psychosis. Some patients may not be able to describe their psychotic symptoms, requiring caregiver input to aid clinicians in recognition. Rating scales can be implemented to aid identification. Clinicians need education about assessing patients with dementia for hallucinations and delusions and about the incidence of psychotic symptoms in different forms of dementia. In addition, many patients with dementia-related psychosis (DRP) receive antipsychotics and are on treatment for over a year, although guidelines recommend tapering after 4 months. Clinicians need education to implement guideline-concordant care that is tailored to the individual patient, incorporating current information on the risks and benefits of nonpharmacologic and pharmacologic interventions for DRP. This activity was designed to meet the needs of participants in CME activities provided by the CME Institute of Physicians Postgraduate Press, Inc., who have requested information on DRP.

Disclosure of Off-Label Usage

Dr Aarsland has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents or device therapies that is outside US Food and Drug Administration–approved labeling has been presented in this activity.

Review Process

The faculty member agreed to provide a balanced and evidence-based presentation and discussed the topic and CME objective during the planning sessions. The faculty’s submitted content was validated by CME Institute staff, and the activity was evaluated for accuracy, use of evidence, and fair balance by the Chair and a peer reviewer who is without conflict of interest.

Acknowledgment

This activity is derived from the teleconference series “Dementia-Related Psychosis: Recognition and Treatment,” which was held in May and June 2020 and supported by an educational grant from ACADIA Pharmaceuticals Inc. The opinions expressed herein are those of the faculty and do not necessarily reflect the opinions of the CME provider and publisher or the commercial supporter.

Faculty Affiliation

Dag Aarsland, MD, PhD
National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation and Institute of Psychiatry, Psychology & Neuroscience at King’s College London, UK

Financial Disclosure

The faculty for this CME activity and the CME Institute staff were asked to complete a statement regarding all relevant personal and financial relationships between themselves or their spouse/partner and any commercial interest. The CME Institute has resolved any conflicts of interest that were identified. No member of the CME Institute staff reported any relevant personal financial relationships. Faculty financial disclosures are as follows:

Dr Aarsland has received research support and/or honoraria from AstraZeneca, Lundbeck, Novartis, Biogen, and GE Health and served as a paid consultant for Lundbeck, Eisai, Heptares, and Mentis Cura.

The Chair for this activity, Clive Ballard, MBChB, MMedSci, MRCPsych, MD, is a consultant for and has received honoraria from Acadia, Roche, Lundbeck, Exevia, AARP, Synexus, and Novo Nordisk; has received grant/research support from Synexus, Novo Nordisk; and is a member of the speakers/advisory boards for Acadia, Roche, AARP, Synexus, and Novo Nordisk.

Accreditation Statement

The CME Institute of Physicians Postgraduate Press, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Credit Designation

The CME Institute of Physicians Postgraduate Press, Inc., designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Note: The American Nurses Credentialing Center (ANCC) and the American Academy of Physician Assistants (AAPA) accept certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by the ACCME.


Introduction

Dementia is a common and disabling syndrome; 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% to 70% of dementia cases,1 followed by vascular dementia (VD) 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 earlier institutionalization, faster cognitive decline, and greater caregiver burden.5 This report will examine the epidemiology and pathophysiology of DRP and communication about psychotic symptoms with patients with dementia (if possible) and their care partners.

Epidemiology of DRP

Prevalence and symptoms. DRP can occur in all dementia types. The prevalence of psychosis among people with dementia is estimated to be greatest in those with DLB and PD; studies have reported the following approximate overall prevalence rates of DRP6:

  • DLB, 75%
  • PD, 50%
  • AD, 30%
  • VD, 15%
  • FTD, 10%

Recurrent visual hallucinations are a core feature of DLB7 and are also a common characteristic of PD dementia.8 Simple hallucinations are rare, with most patients experiencing complex hallucinations daily, normally lasting minutes. The experiences, typically perceived by patients as unpleasant, often feature people or animals (AV 1).8,9


AV 1. Illusions and Visual Hallucinations

Based on Ffytche et al.9


A longitudinal study10 of patients living with AD reported that, over 3 years, 23% of patients developed only delusions, 9% developed only hallucinations, and 19% developed both delusions and hallucinations. A review11 of 55 studies showed that psychosis occurred in about 40% of patients with AD, and delusions occurred more frequently (36%) than hallucinations (18%).

Research conducted in Cache County, Utah, screened 5,092 elderly residents for dementia; of the 329 participants with dementia, 65% had AD, 19% had VD, and 16% had another dementia diagnosis.12 When Neuropsychiatric Inventory (NPI) domains were compared between the participants with AD and VD, hallucinations were equally common, at about 13% each, but delusions were much more common in AD than VD (22% versus 8%, respectively).12 Another Cache County report5 found a prevalence of delusions and/or hallucinations in 27% of the participants with AD and 15% of those with VD. This report also provided details on the specific kinds of delusions and hallucinations in these patients (AV 2).5


AV 2. Prevalence of Types of Delusions and Hallucinations in Patients With Psychosis and Alzheimer Disease or Vascular Dementia

Data from Leroi et al.5


A Norwegian study13 of patients with mild dementia reported more hallucinations and greater associated caregiver distress for patients with mild DLB versus those with mild AD. DRP can appear in patients even before they develop dementia. A cross-sectional study14 using data from a Norwegian national registry of memory clinics examined NPS in patients with mild cognitive impairment (MCI), mild AD, and moderate-severe AD. Both delusions and hallucinations occurred in people at the MCI stage—approximately 14% had delusions and 8% had hallucinations.14

Frequency, persistence, distress, and insight. In addition to the prevalence of DRP, clinicians must also consider its frequency and persistence, the distress it causes patients, and their degree of insight into their symptoms. A study15 of 83 patients with dementia and at least 1 psychotic symptom found that most patients experienced psychotic symptoms at a frequency between daily and weekly. Only 1 patient had full insight, while 24 had no insight and acted upon their psychotic symptoms. Thirty‐seven patients were mildly distressed by their psychotic symptoms, and 14 were severely distressed. Delusions and hallucinations may increase in frequency over time and be persistent in some individuals with dementia,16,17 and these features can vary depending on the type of dementia. For example, in a study18 of patients with DLB (N = 82) and AD (N = 132), visual hallucinations were significantly more likely to persist in those with DLB (P < .0001).

One longitudinal cohort study19 based on the Norwegian cohort assessed NPS (using the NPI) in patients with mild dementia for 5 years. Severe NPS were common at the time of dementia diagnosis, and overall severity increased moderately over 5 years. At least once during follow-up, 49% of participants scored ≥ 36 on the NPI total score, which is above the score considered to warrant antipsychotic treatment in trials. Among participants with at least 1 hallucination, 69% had persistence, meaning that it was present at the next follow-up; in those who had had at least one delusion, it persisted in 53%. Individual symptoms tended to fluctuate over time. Patients with AD showed a small increase in hallucinations and delusion symptoms over time, whereas in those with DLB, symptoms decreased. Those with DLB had a significantly higher frequency of hallucinations than those with AD (P < .001). However, these are group findings, and DRP tends to fluctuate in individual patients. For example, in an analysis based on 12-years of follow-up20 of patients with AD and DLB who received annual NPI assessment, results showed a highly individual course of NPS, with most symptoms presenting as a single episode or a relapse. A stable course was less common, especially in DLB.

Pathophysiology of DRP

The knowledge base for the pathophysiology of DRP is mainly derived from relatively small and select patient cohorts, meaning that findings should be viewed with caution. However, it is clear that a complex interplay of factors can contribute to delusions and hallucinations in people with dementia, and these include psychological, social, biological, neurochemical, neuropathological, and genetic factors (AV 3).21–24


AV 3. Factors Contributing to Psychotic Symptoms in Patients With Dementia

Data from Cerejeira et al,21 El Haj et al,22 Cohen-Mansfield et al,23 and Targum.24


Neuroimaging is a key factor to understanding the mechanisms of underlying symptoms. A study by Qian and colleagues25 used functional magnetic resonance imaging (fMRI) to test for differences in resting brain function between patients with delusions (N = 15) and without delusions (N = 15). The patients with delusions showed significantly reduced connectivity within areas of the default mode network (DMN), specifically the left inferior parietal lobule, compared to patients without delusions. Because the DMN is believed to be involved in internally focused tasks (eg, self-monitoring, autobiographical memory retrieval, mind-wandering) and social cognition tasks, reduced connectivity of the DMN could hinder these functions and result in delusional thinking.

A study26 of patients with DLB examined the relationships between persistent psychiatric symptoms (visual hallucinations, delusions, depression) and plaques, tangles, and Lewy bodies. The results showed that the presence of neocortical Lewy bodies increased the frequency of both hallucinations and delusions, and a low tangle count was the main correlate of persistent visual hallucinations in DLB.

The PD psychosis spectrum has a continuum, starting with minor illusions, progressing to visual hallucinations with insight and then with loss of insight, and culminating in delusions and nonvisual hallucinations.9 Although the symptoms progress over time, they are not necessarily associated with the same underlying mechanisms.9 Minor illusions and hallucinations appear to be associated with somnolence, severity of PD motor symptoms, and dysfunctional brainstem eye movement control mechanisms and subcortical and cortical motion pathways, including dorsal stream areas in the visual parietal lobe. Subsequent formed visual hallucinations with insight appear to have basal forebrain involvement. Some potential mechanisms involved in visual hallucinations include hyper-dopaminergic activity, imbalanced cholinergic neurotransmission, dysfunctional visual pathways, sleep disturbances, and cognitive impairment.27 The 3 proposed mechanistic models of visual hallucinations include (1) disturbed balances between top-down and bottom-up aspects of visual perception, (2) chronic deafferentation causing hyperexcitability to the cortical structures involved in vision, and (3) misattribution of internal imagery.28 Multimodal hallucinations (ie, involving sensory modalities other than sight), delusions, and loss of insight are associated with widespread cortical Lewy body pathology.9

The mechanisms involved in the emergence of NPS in AD remain unclear but may include neocortical changes, serotonergic changes (eg, 5-HT2C receptor), and dopaminergic polymorphisms, which play a key role in mania and schizophrenia.29 A large study30 using the National Alzheimer’s Coordinating Center database reviewed clinically diagnosed AD patients (cAD) with neuropathologically definite AD cases (npAD). Psychotic symptoms were found in 34% of the cAD group and 37% of the npAD group. In both groups, hallucinations were associated with greater cognitive and functional impairments, while patients with delusions showed less impairment. The presence of psychosis was related not to AD pathology but rather to Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors.

One form of vascular pathology, cerebral amyloid angiopathy (CAA), contributes to neurodegeneration, and the Norwegian cohort study31 examined its relation to psychotic symptoms in patients with moderate AD and DLB. The main finding was an association between advanced CAA and small vessel disease with severe psychotic symptoms in patients with moderate AD. This finding is consistent with several studies indicating that vascular pathology is a contributing factor to psychosis.32,33

Researchers are also learning more about genetic contributions to psychosis. For example, in a study34 that examined psychotic symptoms in patients with FTD, 34% of FTD patients showed psychotic features. Patients with FTD and the C9orf72 gene expansion had higher rates of psychotic symptoms than non-carriers of the gene expansion (64% vs 26%; P = 0.006).

Case Practice Question

Antonio, a 72-year-old artist who has complained about mild memory problems, reports seeing people walking in his garden for several months. He has called the neighbors, but they have never seen anyone. Antonio has maintained good physical health throughout his life but is now wondering if he has dementia. Until further evaluation is completed, which diagnosis is more likely based on Antonio’s presentation?

a. Alzheimer disease

b. Dementia with Lewy bodies

c. Vascular dementia

d. Frontotemporal dementia

Discussion of the Case Practice Question

Preferred response: b. Dementia with Lewy bodies

Explanation: Antonio is probably experiencing visual hallucinations, as his neighbors have not seen anyone in his garden. While visual hallucinations can occur in every dementia type, they are a core feature of DLB and often appear early in the disease course.8,35

Discussing Psychosis With Patients and Care Partners

Family Perspectives

Psychotic symptoms can be upsetting for patients and for care partners. Some have described the following experiences:

“People do look at me and they think there’s nothing wrong with me. But they don’t see it all. They don’t see me at night when I’m having hallucinations that I can see my mum and dad….It is the worst disease in the world. It is the loneliest disease in the world.”36

“My mother periodically experiences delusions and hallucinations that my father and I left her or are trying to get rid of her. She often says that my father does not care about her, and on occasion she gets physical with my father… I tried working on my patience and coping skills, but it is clear that I have reached a breaking point with events like this.”37

“My mother thought there were children in the house and she would look for them and worry about them, but I told her they were fine and must be playing together.”38

A study39 analyzed qualitative data provided by family caregivers regarding reasons behind the delusions of patients with dementia. Three broad reasons given to explain patients’ delusions were environmental factors (eg, changes in the patient’s environment, caregiver’s behavior, unmet needs), personal factors (eg, personality, past experiences, negative feelings), and dementia factors (eg, memory problems, disorientation). Results revealed that what is often classified as a delusion is disorientation combined with an attempt to fill in gaps caused by cognitive impairment. A delusion of abandonment may be related to a need for social contact. Major environmental changes were a common explanation for the delusion of “this house is not my home,” and theft delusions were often explained as resulting from dementia-induced memory deficits that interfered with the patient finding possessions. Clinicians must probe factors that contribute to DRP in discussions with the patient (if possible) and the care partners. Determining a key antecedent of what is thought to be a delusion may be helpful in providing effective interventions.39 Care partner explanations should be supplemented by clinicians’ direct questions.

Thus, 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. It is also helpful to explain that this is a common part of the disease and does not mean that they are “crazy” or have acquired an additional disease. It is usually not helpful for clinicians or carers to argue with the patient or try to convince him or her that these thoughts or sensory impressions are not real; it is more helpful, rather, to try to understand and acknowledge the patient’s emotional reaction and gently try to direct attention to other aspects or ideas.

Conclusion

Delusions and hallucinations occur in all forms of dementia and at all stages. They tend to increase with duration and severity of the disease, but there are also individual fluctuations. While a variety of symptoms can occur in all dementia types, visual hallucinations are particularly common in patients with DLB and PD dementia. Mechanisms behind DRP are multifactorial, including different neurobiological factors as well as environmental, social, and psychological factors. If key antecedents of symptoms can be determined through communication with care partners and possibly the patient, then clinicians can offer effective interventions.

Clinical Points

  • Consider environmental, social, and psychological factors behind DRP
  • Recognize that DRP symptoms tend to fluctuate in individual patients
  • Be prepared to discuss the types of delusions and hallucinations that occur in different types of dementia with patients and their caregivers
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