Managing Behavioral and

Psychological Symptoms of
Dementia
a, a,b
Lauren B. Gerlach, DO *, Helen C. Kales, MD

KEYWORDS
 Dementia  Behavioral and psychological symptoms of dementia
 Nonpharmacologic treatment  Caregivers

KEY POINTS
 Behavioral disturbances are universally experienced by people with dementia and cause
significant impairment in quality of life, health care outcomes, and caregiver burden.
 Antipsychotics are typically used to treat such behaviors, although evidence to support
their use is modest and associated with harms, including increased mortality. There are
currently no FDA-approved medications for treatment of behavioral disturbances in
dementia.
 Nonpharmacologic interventions, better termed “ecobiopsychosocial,” are recommen-
ded first line and should target patient with dementia factors, caregiver factors, and envi-
ronmental factors.
 The DICE (Describe, Investigate, Create, Evaluate) approach can provide a structured
approach to investigating and treating behavioral and psychotic symptoms of dementia
(BPSD).
 Pharmacologic measures should be considered first line for three specific scenarios: ma-
jor depressive disorder with or without suicidal ideation, psychosis causing harm or poten-
tial for harm, and aggression with risk to self or others.

INTRODUCTION

Alzheimer disease and related dementias are among the most costly and distressing
medical conditions for patients and their caregivers. In 2016 it was estimated that
there were 5.2 million Americans with Alzheimer disease, with that number projected
to increase to 13.8 million by 2050.1,2 Alzheimer disease is currently the sixth leading
cause of death within the United States and has costs of more than $236 billion

This article originally appeared in Psychiatric Clinics, Volume 41, Issue 1, March 2018.
Disclosure: The authors have nothing to disclose.
a
Program for Positive Aging, Department of Psychiatry, University of Michigan, 4250 Plymouth
Road, Ann Arbor, MI 48109, USA; b Center for Clinical Management Research, VA Ann Arbor
Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA
* Corresponding author.
E-mail address: glauren@med.umich.edu

Clin Geriatr Med 36 (2020) 315–327

https://doi.org/10.1016/j.cger.2019.11.010 geriatric.theclinics.com
0749-0690/20/ª 2019 Published by Elsevier Inc.
316 Gerlach & Kales

annually.1 Families and caregivers of patients with dementia are greatly affected
because most individuals with dementia are cared for within their home by family
and friends.3,4
Although dementia is often thought of as a disease of memory, neuropsychiatric (eg,
behavioral and psychological symptoms) and social deficits are nearly universal
across all types and stages of dementia.5 The Cache County study found that over
the course of dementia, 97% of individuals with dementia experience one or more
behavioral disturbance.6 These behavioral and psychological symptoms of dementia
(BPSD) can often be the most challenging for caregivers and families.

BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA

BPSD, also known neuropsychiatric symptoms, occurs in clusters or syndromes iden-

tified as depression, psychosis (delusions and hallucinations), agitation, aggression,
apathy, sleep disturbances, and disinhibition (socially and sexually inappropriate be-
haviors) (Table 1).7 Agitation is often a broad category and it is helpful to clarify the
specific behaviors that are of concern. Agitation can include restlessness, pacing,
arguing, disruptive vocalizations, and rejection of care (eg, bathing, dressing, groom-
ing).7 Aggression is typically defined as verbal insults, such as shouting, and physical
aggression, such as hitting and biting others, and throwing objects. In addition, there
are numerous behaviors (eg, arguing, repetitive questions, resistance to care) that do
not fit neatly into any symptom category, but are nonetheless burdensome to
caregivers.8
Although BPSD is seen throughout the course of dementia illness, symptoms may
occur intermittently or fluctuate greatly in severity. These behaviors are found in all
types of dementia; however, some symptom clusters are more common in specific
types of dementia. For instance, psychosis and visual hallucinations are more typical
features of Lewy body dementia. Additionally, symptoms such as disinhibition,
apathy, and social inappropriateness are often seen within frontotemporal dementia.

Table 1
Types of behavioral and psychological symptoms of dementia

Agitation Walking aimlessly

Pacing
Trailing
Restlessness
Repetitive actions
Aggression Aggressive resistance
Physical aggression
Verbal aggression
Apathy Withdrawn
Lack of interest
Amotivation
Depression Sad
Tearful
Hopeless
Anxiety
Guilt
Psychosis Hallucinations
Delusions
Misidentifications
Disinhibition Socially and sexually inappropriate behavior
 Managing Symptoms of Dementia 317

Although memory impairment is the hallmark of dementia, BPSD often can create
the most challenges for patients, their caregivers, and providers.9 These behaviors
can change the trajectory for patients and are associated with faster disease progres-
sion10 and increased morbidity and mortality.11 Behavioral disturbances can often
trigger nursing home placement and hospitalization, resulting in increased hospital
length of stay.11,12 BPSD is also associated with poor caregiver outcomes including
increased caregiver stress and depression and reduced caregiver employment.13
Roughly one-third of total dementia care costs are attributed to management of
BPSD, related to increased service utilization, care costs, and caregiver time.14

CAUSES OF BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA

Many factors have been found to be associated with the development of BPSD. Un-
derlying many of these behaviors, there are fundamental changes and neurodegener-
ation in the brain of persons with dementia in centers that control cognition and
emotion. Breakdown in this brain circuitry caused by dementia can impact the ability
of the person with dementia to interact with others and their environment.15 This can
often lead to increased vulnerability to stressors, which can occur at the patient level,
with the caregiver, and in the environment manifesting as behavioral disturbances.7 As
dementia progresses and communication becomes more difficult, behaviors should
be seen as communications and caregivers need to rely more on a combination of
strategies to understand what needs are being communicated. Fig. 1 shows a

Fig. 1. Causes of behavioral and psychological symptoms of dementia.

318 Gerlach & Kales

conceptual model that details the myriad of causes of BPSD, which include person
with dementia factors, caregiver factors, and environmental factors.

Person with Dementia Factors

Patient factors, such as an undiagnosed medical issue, can contribute to the develop-
ment of behavioral disturbances. Medical issues, such as urinary tract infections, hy-
pothyroidism, anemia, constipation, and pneumonia, are common culprits. In a study
of community-dwelling older adults with dementia more than a third of patients were
found to have undetected medical illnesses associated with behavioral distur-
bances.16 Changes in central nervous system active medications, such as anticholin-
ergic medications and opioids, and drug-drug interactions can lead to behavioral
disturbances. Inadequate assessment and treatment of pain can lead to BPSD17
with studies showing that empiric treatment of presumed pain can reduce agitation
in residents of nursing homes with moderate to severe dementia.18
Additionally, premorbid personality traits, personality disorders, and psychiatric
illness do not necessarily go away or diminish in the setting of a dementia diagnosis.
Further disruptions in the neurocircuitry involved in the prefrontal cortex may worsen
long-standing behavioral patterns caused by loss of “gating” or “top down inhibi-
tion.”15,19 Lastly, behaviors can be expressions of unmet needs or goals (physical,
psychological, emotional, social).20 Physical needs may include basic needs, such
as thirst, hunger, or toileting. As patients with dementia lose the ability to communicate
needs verbally, a trial and error approach by caregivers is needed to learn what the
behavior might be representing.

Caregiver Factors
Dementia caregivers have higher levels of stress, lower levels of well-being, and
worse physical health than noncaregivers and other caregivers.21 Additionally care-
givers of patients with BPSD have high rates of depression and anxiety.1 Behavioral
disturbances in patients are triggered or worsened when a caregiver is stressed or
depressed.22 Negative communication styles, such as anger, screaming, or an
overly harsh tone, may also exacerbate behaviors. Caregivers may not understand
what the patient with dementia can do at the particular stage of their illness and
there can be a mismatch of expectations. Education to caregivers that a patient’s
behaviors are not volitional and that patients are not “doing this on purpose” are
beneficial.

Environmental Factors
The environment is thought of interacting layers that comprise objects (items in the
home), tasks (that compose activities of daily living), social groups, and culture (values
and beliefs related to care in the home).7 Individuals with dementia have difficulty pro-
cessing and responding to stimuli in the environment. This lower stress threshold can
lead to higher levels of frustration. Stress for patients with dementia may be increased
by changes in routine or environment, overstimulation or understimulation in the envi-
ronment, and demands that exceed functional ability.23

CURRENT TREATMENT

Given the complexity and multiple causes of BPSD, a “one-size fits all” treatment
approach does not exist. It is important to understand the cause of symptoms, and
knowing the underlying cause directs treatment. For instance, a urinary tract infection,
pain, issues with caregivers, and psychosis are all approached differently.
 Managing Symptoms of Dementia 319

Currently there are no Food and Drug Administration–approved medications for treat-
ment of BPSD and all medications are considered off-label. Despite this, medications
are often prescribed for treatment of BPSD and in real-world treatment settings patients
with BPSD often receive an antipsychotic medication. Of all the drugs used for behav-
iors, antipsychotics do have the strongest evidence base, although the effect size is
modest (0.13–0.16).24,25 Any benefit must be balanced against risk of adverse events
including mortality in this often medically frail population.26–28 Based on mortality con-
cerns, the FDA issued black box warnings for increased risk of mortality with use of atyp-
ical (2005) and typical (2008) antipsychotics in patients with dementia.26,29 Causes of
increased mortality are thought to be cardiovascular or cerebrovascular events and
pneumonia.28 Commonly used alternatives to antipsychotics, such as benzodiazepines
and valproic acid, have even less evidence of positive risk/benefit ratios with no evidence
for efficacy of these agents for treatment of BPSD other than sedation.7

NONPHARMACOLOGIC OR ECOBIOPSYCHOSOCIAL TREATMENT

Nonpharmacologic treatments for BPSD (better stated as ecobiopsychosocial) can

include a wide array of interventions including behavioral, environmental, and care-
giver supportive interventions.30 Ecobiopsychosocial treatments are endorsed by
multiple professional societies as first-line treatment for management of BPSD
including the American Psychiatric Association, American Geriatrics Society, and
American Association for Geriatric Psychiatry.31,32 However, this has not been trans-
lated to real-world care because of many factors including lack of provider training,
time required to implement interventions, lack of reimbursement, and heterogeneity
of interventions.7 Behavioral interventions targeted at the person with dementia may
include reminiscence therapy (discussion of past experiences), aromatherapy, Snoe-
zelen (soothing and stimulating environment), and acupuncture.33,34 Studies have
demonstrated inconsistent support for the overall efficacy of these interventions in
reducing BPSD.35 Behavioral interventions focused on the environment may include
correcting overstimulation or understimulation, addressing safety problems,
increasing activity and structure, and establishing routine. There has been growing ev-
idence for the role of the environment in preventing and reducing behaviors but there
are few randomized controlled trials.36
The behavioral interventions with the most evidence to support reduction in BPSD
are caregiver-supportive interventions. These interventions typically include problem-
solving with the caregiver to identify modifiable causes of behaviors and enhanced
communication between the patient and caregiver dyad. A meta-analysis of 23 ran-
domized controlled trials with family caregiver interventions found these interventions
significantly reduced BPSD, with an effect size greater than that for antipsychotics for
agitation/aggression or cognitive enhancers for cognitive symptoms.37

THE DESCRIBE, INVESTIGATE, CREATE, EVALUATE APPROACH

The Describe, Investigate, Create, Evaluate (DICE) approach is an assessment and

management algorithm created by a national multidisciplinary expert panel. Using
an organized assessment approach or algorithm, such as DICE, can help providers
integrate prevention, assessment, and management of BPSD.38 The DICE approach
can assist providers and caregivers in evaluation and management of BPSD and in-
cludes consideration of possible etiologies, includes caregivers, integrates pharmaco-
logic and nonpharmacologic interventions, and has flexibility to use in various care
settings (Fig. 2). To expand on and detail the DICE approach it is helpful to consider
the following case example:
320 Gerlach & Kales

Fig. 2. The DICE approach. (Adapted from Kales HC, Gitlin LN, Lyketsos CG. Assessment and
management of behavioral and psychological symptoms of dementia. BMJ 2015;350:h369;
with permission.)

Mr N is a 65-year-old married man with a history of early onset Alzheimer disease. He

lives at home with his wife who is 55 years old and serves as his primary caregiver. He
began experiencing memory loss 5 years ago and a recent Montreal Cognitive Assess-
ment was 10 out of 30. His wife reports lately Mr N has been irritable and verbally
aggressive. His wife feels as though she is “walking on eggshells.” His primary care
 Managing Symptoms of Dementia 321

physician refers Mr N to see a geriatric psychiatrist, requesting a medication to calm Mr

N down.

Step 1: Describe
The first step of the DICE approach is to gather a detailed description of the problem-
atic behavior and the context in which it occurs. This may involve a discussion with the
patient’s caregiver and patient with dementia if possible to understand the behaviors
of concerns, identify antecedents, and other potentially modifiable factors. A full
description of behavior goes beyond “agitation” (which, it can be argued is as nonspe-
cific as “shortness of breath”) and gives a full contextual picture (who, what, why,
when, where). Thus, with such a full description, “agitation” becomes “anxiety and
resistance to getting a daily bath” and leads directly to possible underlying causes
in Step 2.
In the case of Mr N we would want to talk with his wife to better understand the be-
haviors that are most concerning. His wife reports Mr N has been verbally aggressive
yelling “Leave me alone!” on a daily basis. He has never been physically aggressive to-
ward his wife but she feels intimidated at times. These episodes of verbal aggression
often occur when trying to get Mr N to medical appointments or take a daily bath. When
asked, Mr N is not aware of these episodes. His wife states that she is stressed trying to
take care of Mr N and she has had to take over all household responsibilities.

Step 2: Investigate
In the investigate stage, it is important to evaluate the possible causes of the problem
behaviors. Patient-related factors, such as medication side effects, pain, medical con-
ditions, and boredom, may be driving such behaviors. Caregiver factors related to a
mismatch between caregiver expectations and patient capabilities, poor communica-
tion, or caregiver burden may contribute to behaviors. Lastly, environmental causes,
such as changes in home environment and overstimulation or understimulation,
may be contributing.
On examination, we note that Mr N is very hard of hearing with his wife stating he
often refuses to wear his hearing aids and hides them throughout the house. He con-
tinues to rub his shoulder throughout the examination, which his wife believes may be
related to an old rotator cuff injury. His wife describes that he often refuses care tasks,
such as bathing, stating, “I think he does this just to make me upset.” His wife acknowl-
edges feeling “completely burnt out,” feeling guilty asking her family for more assis-
tance. She admits when stressed her communication style can be negative and
scolding. When asked about the daily routine, Mr N spends most of his day at home
watching television while his wife babysits the grandchildren. Previously an avid golfer
and runner, Mr N now has limited activity and exercise during the day.

Step 3: Create
In the create stage the provider, caregiver, and team collaborate to create and imple-
ment a treatment plan. This could include responding to physical problems, improving
communication with patient/caregiver dyad, and ensuring that the environment is
safe.
For Mr N, we rule out any acute medical issues that may be contributing to his symp-
toms, such as a urinary tract infection. Additionally, we coordinate with his primary care
physician to allow for more optimal control of his shoulder pain; this may include a
standing dose of a pain medication for a time because he may forget or not be able
to ask for an as-needed medication dose. We should also try to ensure that he is wear-
ing his hearing aids. Given Mr N’s previous level of physical activity, we work toward
322 Gerlach & Kales

structuring routine and activities during the day that are meaningful to him and tailored
to his interests. His wife is provided with education regarding BPSD and calm commu-
nication approaches. We teach her to “relax the rules,” suggesting that bathing does
not need to occur daily. We prescribe respite services and try to get Mr N’s family
more involved, encouraging his wife to take care of her own medical and mental health
needs.

Step 4: Evaluate
Lastly, providers and caregivers work to evaluate whether the interventions developed
in the “create stage” have been implemented by the caregiver and are safe and effec-
tive. Any unintended side effects or consequences of the interventions should be
brought to the patients’ provider and new techniques can be trialed.
In the evaluation stage, we assess changes to Mr N’s behaviors once his pain is bet-
ter controlled and routine is structured into the day. We discuss with his wife which in-
terventions were most helpful, which interventions failed to improve symptoms, and
whether any unintended consequences or side effects were noted with any of the bio-
psychosocial interventions.

PLACE OF PSYCHOTROPICS IN DESCRIBE, INVESTIGATE, CREATE, EVALUATE APPROACH

Currently there are no FDA-approved pharmacotherapies for treatment of BPSD.

However, psychotropic medications are often prescribed off-label for primary treat-
ment of BPSD.39 Current psychotropic medication classes most commonly used in
BPSD include antipsychotics, antidepressants, anticonvulsants (including valproic
acid and derivatives), benzodiazepines, and cholinesterase inhibitors. Although in
real-world settings such medications are often used first line and choice is targeted
to the symptom cluster that is most problematic (eg, use of antidepressants for treat-
ment of depression, antipsychotics for treatment of delusions or agitation, and anti-
convulsants for mood lability), such practice is decidedly not evidence based (eg,
there is no evidence for the symptom cluster approach or for the efficacy of such med-
ications as valproic acid and derivatives for BPSD). Psychotropic medications should
be considered first line if imminent risk is present for (1) major depression with or
without suicidal ideation, (2) psychosis causing harm or potential for harm, and (3)
aggression with risk to self or others.38 Psychotropic medications rarely help for
such behaviors as unfriendliness, poor self-care, memory problems, inattention/
apathy, repetitive verbalizations, and wandering.7

Antipsychotics
Of the agents used to treat BPSD, antipsychotics do have the strongest evidence
base, although the effect size is moderate (0.13–0.16).7 The largest trial evaluating
antipsychotic use in patients with dementia, the Clinical Antipsychotic Trial of Inter-
vention Effectiveness-Alzheimer’s Disease (CATIE-AD) trial, of 421 subjects with psy-
chosis, aggression, or agitation failed to find improved outcomes over placebo.40 The
2005 and 2008 black box warnings were based on findings of a 1.6- to 1.7-fold in-
crease in mortality for antipsychotics as compared with placebo in patients with de-
mentia.26,29 Antipsychotic medications are associated with other side effects
including cognitive worsening, somnolence, abnormal gait/falls, and stroke.41 QTc
prolongation, metabolic effects (weight gain, dyslipidemia, diabetes), and movement
disorders (parkinsonism, dystonia, tardive dyskinesia) are additional concerns.42
Prescribing of antipsychotic medications for BPSD follows the general prescribing
principles for geriatric psychiatry: “start low and go slow.” Starting doses of
 Managing Symptoms of Dementia 323

antipsychotic medications are generally one-fourth to one-half of typical starting

doses for adults (Table 2). For patients with Parkinson disease dementia or Lewy
body dementia, special caution is required with use of antipsychotic medications
because these patients are sensitive to the motor side effects of antipsychotic medi-
cations.7 In these patients preference is given to use of cholinesterase inhibitors, such
as rivastigmine, as first-line treatment of BPSD.43 For patients who fail to respond to
cholinesterase inhibitors, preferred agents included quetiapine and clozapine given
lower blockade of the dopamine 2 receptor and less risk for extrapyramidal side ef-
fects, although these medications are still associated with increased mortality.44 In
2016 pimavanserin was approved by the FDA for treatment of Parkinson disease psy-
chosis.45 This antipsychotic has a novel mechanism of action with no appreciable
dopamine 2 blockade or risk for extrapyramidal symptoms, working as a selective in-
verse agonist at the serotonin 2A receptor.46 However, pimavanserin still carries the
same black box warning for increased mortality in use with patients with dementia
and can cause QT prolongation.
Antidepressants
Antidepressant medications may have efficacy for treating agitation but have not
shown consistent benefits for treating depression in dementia over five randomized
controlled trials.47 Antidepressant mediations are also associated with adverse events
including sleep changes, nausea, vomiting, hyponatremia, and potential for QT pro-
longation with citalopram.7 Low doses of the antidepressant trazodone (12.5–
25 mg) can be used at times for treatment of agitation and anxiety in lieu of antipsy-
chotic medication or benzodiazepines. In 2014 the Citalopram for Agitation in Alz-
heimer Disease (CITAD) study randomized patients to receive citalopram, finding
patients treated with citalopram had significant improvements in agitation, caregiver
stress, improved performance of activities of daily living, and reduction in use of a
rescue medication (lorazepam) as compared with placebo.48 However, patients
treated with citalopram were found to also have worsening cognition and QT prolon-
gation, which may limit its use.
Anticonvulsants
Available studies evaluating use of anticonvulsants, such as valproic acid, have not
shown clear evidence for benefit and are associated with increased risk of mortal-
ity.49,50 Two small studies looking at carbamazepine showed some benefit for treat-
ment of agitation.51,52 However, these medications are associated with serious risks
including hepatitis, pancreatitis, and thrombocytopenia for valproic acid, and agranu-
locytosis and pancytopenia for carbamazepine.53 Anticonvulsant agents are helpful at

Table 2
Starting and dose range of atypical antipsychotics for treatment of behavioral and
psychological symptoms of dementia

Antipsychotic Starting Dose Dose Range

Risperidone 0.25–0.5 mg q h 0.25–2 mg/d
Quetiapine 12.5–25 q h 25–600 mg/d
Olanzapine 1.25–5 mg q h 2.5–20 mg/d
Aripiprazole 1–2 mg daily 2.5–20 mg/d
For Lewy body dementia or Parkinson disease dementia
Quetiapine or clozapine 6.25–12.5 mg 25–350 mg/d
324 Gerlach & Kales

times at addressing mood instability and in the setting of prolonged QT where antipsy-
chotic medications should be avoided.
Benzodiazepines
The use of benzodiazepines is associated with significant risks including increased
cognitive impairment, disinhibition, falls, sedation, and respiratory suppression.54
Given the lack of evidence of supporting use of benzodiazepines over placebo or other
medications, use is not recommend outside of an acute behavioral crisis.55,56
Cholinesterase Inhibitors and Memantine
Cholinesterase inhibitors and memantine are the primary treatment of the cognitive
symptoms of Alzheimer disease. However, some studies have suggested that these
medications may also help to alleviated BPSD. A systematic review of cholinesterase
inhibitors found a significant although small reduction in BPSD (overall reduction of
1.72 points on the 120-point neuropsychiatric inventory).57 Studies for use of meman-
tine have been equally mixed, with a recent trial demonstrating no benefit over pla-
cebo in reducing agitation in Alzheimer disease.58 Cholinesterase inhibitors are
associated with gastrointestinal side effects, such as diarrhea, nausea, and vomiting,
and symptomatic bradycardia.59 Side effects of memantine include headache, confu-
sion, and dizziness.60

SUMMARY

Although cognitive impairment is the hallmark of dementia, behavioral disturbances

are universally experienced by people with dementia throughout the course of the
illness. BPSD causes a significant negative impact on quality of life, health care out-
comes, caregiver stress/burden, and health care costs. However, treatment of
BPSD may help to change the trajectory for patients and their caregivers. Nonpharma-
cologic treatments have been recommended as first-line treatment of BPSD by mul-
tiple professional organizations and expert panels and should target patient with
dementia factors, caregiver factors, and environmental factors. Despite no medica-
tions having an FDA indication for management of BPSD, psychotropic medications
are often prescribed off-label without significant evidence to support their use. The
DICE approach can provide a structured method to investigate and treat BPSD with
flexibility to use in multiple treatment settings. Treating clinicians need to consider
the full biopsychosocial complexity of BPSD to best approach and guide care.

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