The goal of this webinar is to enable healthcare clinicians to implement a comprehensive approach to non-pharmacologic and pharmacologic management of dementia-related behaviors for the benefit of patients and their caregivers.

1. Evaluation and Management
of Behaviors in Persons with
Cognitive Impairment
Joseph W. Shega, MD

2. CE Provider
Information
VITAS Healthcare programs are provided CE credits for
their Nurses/Social Workers and Nursing Home
Administrators through: VITAS Healthcare Corporation
of Florida, Inc./CE Broker Number: 50-2135. Approved
By: Florida Board of Nursing/Florida Board of Nursing
Home Administrators/Florida Board of Clinical Social
Workers, Marriage and Family Therapy & Mental
Health Counseling.
VITAS Healthcare programs in Illinois are provided CE
credit for their Nursing Home Administrators and
Respiratory Therapists through: VITAS Healthcare
Corporation of Illinois, Inc./8525 West 183 Street, Tinley
Park, IL 60487/NHA CE Provider Number: 139000207/RT
CE Provider Number: 195000028/Approved By the
Illinois Division of Profession Regulation for: Licensed
Nursing Home Administrators and Illinois Respiratory
Care Practitioner.

3. CE Provider
Information
(Cont.)
VITAS Healthcare, #1222, is approved to offer social work
continuing education by the Association of Social Work Boards
(ASWB) Approved Continuing Education (ACE) program.
Organizations, not individual courses, are approved as ACE
providers. State and provincial regulatory boards have the final
authority to determine whether an individual course may be
accepted for continuing education credit. VITAS Healthcare
maintains responsibility for this course. ACE provider approval
period: 06/06/2018 – 06/06/2021. Social workers completing this
course receive 1.0 ethics continuing education credits.
VITAS Healthcare Corporation of California, 310 Commerce,
Suite 200, Irvine, CA 92602. Provider approved by the California
Board of Registered Nursing, Provider Number 10517, expiring
01/31/2021.
Exceptions to the above are as follows: AL: No NHAs, DE: No
NHAs, DC: No NHAs, GA: No NHAs, KS: No NHAs, NJ: No
NHAs, OH: No NHAs, PA: No NHAs, TX: No NHAs, VA: No
NHAs, WI: No NHAs and Nurses are not required – RT only
receive CE Credit in Illinois.

4. By the end of this presentation, you will
be able to:
• Differentiate among delirium, terminal
restlessness, and dementia-related
agitation and aggression
• Identify and treat contributors to
behaviors in dementia
• Implement effective non-pharmacologic
management approaches to behaviors
in dementia
• Incorporate pharmacologic treatment
strategies to manage behaviors
in dementia
Objectives

5. • Current estimate: 5.1 million in US have
dementia (ADAMS Study)
– 3.2 million women
– 1.8 million men
• Projected for 2050: 14 million Americans
with dementia
• One in three women will develop dementia
during her lifetime
• Almost one-third of people over age 85
have dementia
• Someone new develops dementia every
67 seconds in the US
Background:
Dementia
Epidemiology

6. • One in three older adults who die each
year have a diagnosis of dementia
• Diagnosis of dementia cuts one’s life
expectancy in half
• Dementia is the fifth-leading cause of
death in persons over 65
• >500,000 deaths a year in US are
attributed to dementia
Background:
Dementia
End of Life

7. Hospice Use
by Primary
Diagnosis
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
1,800,000
1992 1998 2005 2014
Other
Kidney disease
Stroke
Chronic lower
respiratory disesease
Alzheimer disease
Heart Disease
Cancer

8. Symptoms
of End-Stage
Dementia
0
5
10
15
20
25
30
35
40
Dyspnea Pain Pressure
ulcers
Aspiration Agitation
ResidentswithSymptoms(%)
Distressing Symptoms
Months before Death (no. of residents alive during interval)
>9-12 (N=67) >6-9 (N=96) >3-6 (N=128) 0-3 (N=177)

9. • 61-year-old with Huntington’s Disease who presents
to the hospice inpatient unit (IPU) with impulsivity
and agitation
- Has not slept in two days; is more confused,
pacing, eating food out of garbage
• Patient recently admitted to hospice with functional
decline, falls, weight loss, dysphagia and
worsening behaviors
• Interventions to date: Haldol 5mg every six hours
and every two hours as needed, mirtazapine 30mg
at night, sertraline 50mg daily, lorazepam 1mg every
six hours and one hour as needed, amantadine
200mg daily
• Urinalysis and bloodwork were unremarkable.
Patient was transferred to the IPU for further
management of impulsivity and agitation
Case 1:

10. • 86-year-old with cerebral atherosclerosis with recent
functional decline
- In the past two weeks: bedbound, fall, stage II
sacrum, poor appetite, weight loss, and increased
agitation/aggression
• Daughter took patient out of ALF after patient hit and
tried to bite several staff
- Patient spends most of the day yelling, swearing,
kicking; is very restless in bed
• Comorbidities: hard of hearing, poor vision, arthritis,
peripheral vascular disease, history of stroke,
hypertension, depression, and heart failure
• Bloodwork and urinalysis were unremarkable.
Patient admitted to hospice and transferred to the
IPU for management of vocalizations and
agitation/aggression.
• Medications: sertraline 100mg daily
Case 2:

11. • Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal restlessness,
and dementia-related behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be treated
and characterize impact on patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment
Guiding
Principles

12. Most
Common
Etiologies of
Dementia
Dementia Diagnosis
Relative
Frequency
Pathophysiology
Alzheimer’s disease 35-55%
amyloid plaques and
neurofibrillary tangles
Mixed: Vascular and
Alzheimer’s disease
25-35%
Combination of
Alzheimer’s disease and
vascular disease
Lewy Body Dementia 0-30% alpha-synuclein protein
Vascular Dementia 10-20%
cortical infarcts, subcortical
infarcts and leukoaraiosis
Frontotemporal Dementia <5% Tau protein

13. • Depression is more common in
vascular dementia
• Hallucinations are seen more often in
Lewy body dementia
– Special consideration ACEI
and antipsychotics
• Frontotemporal dementia often exhibits
executive control loss
– Disinhibition
– Wandering
– Social inappropriateness
– Apathy
• Behaviors increase in frequency with all
conditions as disease progresses
Dementia
Etiology
Considerations

14. • Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal
restlessness, and dementia-related
behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be
treated and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment
Guiding
Principles

15. Definition of
Delirium
AND
plus either
Acute Onset and
Fluctuating Course
Inattention
Disorganized
Thinking
Altered Level of
Consciousness (LOC)
DELIRIUM

16. Terminal
Restlessness
16
THE USUAL
ROAD
THE DIFFICULT
ROAD

17. Thought and
Perceptual
Disturbances
• Delusions
• Paranoia
• Hallucination
Mood Disturbances
• Anxiety
• Depression
• Irritability
Dementia
Behaviors
Activity Disturbance
• Agitation
• Aggression
• Wandering
• Purposeless
hyperactivity
• Apathy
• Impulsivity
• Socially inappropriate
behavior
• Sleep problems
• Repetitive behavior

18. • Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal
restlessness, and dementia-related
behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be treated
and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment
Guiding
Principles

19. Contributors
to Behaviors
Contributor Causes Approach
Physical symptom Pain, SOB Opioid
Psychological symptom Depression, anxiety SSRI, SNRI CBT
Medical illness Delirium, infection, constipation Treat condition
Unmet need Hunger, thirst, cold Attend to need
Sensory impairment Poor vision/hearing Adaptive
Environment Under-/over-stimulation Modify
Pharmacologic Dig, caffeine, benzo Discontinue
Dementia AD, Mixed, LBD AChEI

20. • Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal
restlessness, and dementia-related
behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be
treated and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment
Guiding
Principles

21. • Patient
– Increased morbidity and mortality
– Increased likelihood of hospitalization
and longer length of stay
– Early placement in a nursing home
• Caregiver
– Stress and strain
– Depression and anxiety
– Reduced income from employment
– Lower quality of life
• Behaviors and their management
contribute to one-third of total dementia-
related costs
Behaviors in
Dementia
and Health-
Related
Outcomes

22. • Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal
restlessness, and dementia-related
behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be treated
and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment
Guiding
Principles

23. • Person with Dementia
– Unmet need; behavior as an
underlying need
– Agitation etiology, remaining abilities, level of
cognitive functioning, and past/present interests
• Caregiver
– Learning and behavioral (ABC)
– Behavior Consequence Reinforces behavior
• Environment
– Environmental vulnerability and reduced stress
thresholds: a mismatch between the setting and
the patient’s ability to deal with it
Dementia
Behavior
Models

24. • Reminiscence therapy (discussion of
past experiences)
• Validation therapy (working through
unresolved conflicts)
• Simulated presence therapy (use of
audiotaped recordings of family
members’ voices)
• Aromatherapy (use of fragrant plant oils)
• Snoezelen®
(placing the person with
dementia in a soothing and stimulating
multi-sensory environment known as a
“Snoezelen room”)
• Cognitive training and rehabilitation
• Acupuncture
• Light therapy
Non-
Pharmacologic
Persons with
Dementia:
Inconclusive
Evidence

25. • Physical activity positively impacts
depression and sleep
• Hand massage
• Personalizing the bathing experience
Non-
Pharmacologic
Persons with
Dementia:
Evidence Exists
in Two or More
Randomized
Clinical Trials
(RCTs)

26. • Problem-solving with a family caregiver
– Identify precipitating and modifiable causes
of symptoms
– Deploy efforts to modify these causes with selected
non-pharmacologic strategies
• Program examples
– REACH II and REACH VA: Coping approaches
and tailored behavioral management
– The Tailored Activity Program (TAP):
Occupational Therapy
– The Advancing Caregiver Training (ACT):
Health Professionals
• A meta-analysis of 23 randomized clinical trials,
involving almost 3,300 community dwelling patients
and their caregivers
– Significantly reduced behavioral symptoms
(effect size 0.34, 0.20 to 0.48)
– Similar to antipsychotics for behavior; similar to
cholinesterase inhibitors for memory
Non
Pharmacologic
Caregivers:
Most Robust
Evidence

27. • Over-stimulation (e.g., excess noise,
people or clutter in the home)
• Under-stimulation (e.g., lack of anything
of interest to look at)
• Safety problems (e.g., access to
household chemicals or sharp objects;
easy ability to exit the home)
• Lack of activity and structure (e.g., no
regular exercise or activities that match
interests and capabilities)
• Lack of established routines (e.g., frequent
changes in the time, location or sequence
of daily activities)
Non-
Pharmacologic
Environment:
Paucity of
RCTs, Positive
Impact

28. Responses
to Non-
Pharmacologic
Interventions
Greater Response
• Higher levels of
cognitive function
• Fewer difficulties
with ADLs
• Speech
• Communication
• Responsiveness
Less Response
• Staff barriers
(refuse to participate)
• Patient in pain

29. • Identify dementia etiology as symptoms and
treatments vary
• Differentiate delirium, terminal restlessness,
and dementia-related agitation
• Evaluate and manage all contributors
to agitation
• Identify the target symptoms to be treated
and characterize impact on patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment
Guiding
Principles

30. Helpful
• Agitation and
aggression
• Psychosis
– Delusions
– Hallucinations
– Paranoia
• Depression
• Irritability
Dementia
Behaviors and
Pharmacologic
Treatment
Not Helpful
• Day/night reversal
• Calling out
• Repetitive behaviors
• Wandering
• Apathy
• Resistance to care

31. Pharmacologic
Treatment of
Agitation
Therapeutic Class Trial Side Effects
Trazodone + RTC Sedation, Hypotension
SSRI (citalopram) + RCT
Nausea, diarrhea, QTc inc
>20mg daily
Dextromethorphan/qui
nidine
+ RCT Falls, dizziness, diarrhea, UTIs
Lorazepam + RCT Sedation, falls, ataxia, agitation
Anti-psychotics + RCT
Stroke, infection, sz, QTc inc,
DM, death
Carbamazepine
Valproic acid
- RCT
- RCT
Sedation, anemia, liver toxicity
Liver toxicity, sedation
NMDA antagonist - RCT/+obs Constipation, dizziness
AChEI - /+RCT/+obs Nausea, dizziness, weight loss
Cannabinoids - RCT Low does used, oral form

32. • Several small randomized controlled trials
indicate benefit
– Cochrane review inconclusive evidence
• Dosing: 25-20 mg BID-TID and q 2hrs
PRN, maximum dose 400mg daily
• Adverse effects:
– Orthostasis, syncope,
hypotension, dizziness
– Priapism
– SIADH
– Somnolence
– QTc prolongation
Trazadone

33. Citalopram
for Agitation
in Alzheimer’s
Disease

34. • QTc prolongation, which is dose-dependent
above 20mg
• Starting dose 10mg up to 40mg daily
• Consider twice-daily dosing
– 10mg daily for two weeks
– 10mg twice daily thereafter
• Other SSRI side effects
• Onset of action within a week in one study
Citalopram
Considerations

35. • Best-studied pharmacologic intervention
for dementia-related agitation
• Moderate efficacy across trials and agents
– Typical antipsychotics
– Atypical antipsychotics
• Substantial side effects
• Black box warning: cerebrovascular events
and death
Antipsychotics

36. Antipsychotics
(Cont.)
Antipsychotic
Recommended
Dose
Formulations Frequency Characteristics
Risperidone 0.5-2.0mg Tab, liquid, IM Twice daily
Extrapyramidal
symptoms
Olanzapine 2.5-15mg tab Daily
Weight gain,
increased sugar
Quetiapine 25-400mg tab
Three times
daily (unless
ER)
Sedating, least
extrapyramidal
Aripiprazole 5-30mg Tab, liquid, IM Daily Less QT
Haloperidol 0.5-5mg
Tab, liquid, IM,
IV, sub q
Twice to four
times daily
Chlorpromazine 10-200mg
Tab, liquid, IV,
rectal
Twice to
three times
daily
Very sedating

37. CATIE-AD

38. CATIE-AD
(Cont.)

39. CATIE-AD
(Cont.)

40. • Modest efficacy for treatment of behaviors
in dementia
– NNT 5 to 14
• Studies usually short duration: 6-12 weeks
• Large placebo effect: 30% on average
• No difference in efficacy between typical
and atypical antipsychotics
• Typical antipsychotics: greater side effects
Antipsychotic
Summary

41. • Binds to GABA receptor in CNS
• Anxiolytic, sedative and hypnotic effects
(anterograde memory)
• Increased risk of adverse events
– Falls
– Cognitive impairment/confusion
– Hip fracture
– Sedation
– Paradoxical agitation
Anxiolytics

42. Agitation and
Dementia:
Lorazepam

43. Pharmacology
Common
Agents
Benzodiazepine Half-life Dosage range
diazepam
20-50 hours
Over 100 OA
2-10mg
2-4 times a day
lorazepam 12 hours
0.5-2mg
2-3 times a day
alprazolam
16 hours
(9-27 range)
0.25-3mg
2-4 times a day
clonazepam 30-40 hours
0.25-5mg
2-3 times a day

44. Dextromethorphan-
Quinidine For
Dementia Agitation
in Alzheimer’s
Disease

45. • FDA-approved for the treatment of
pseudobulbar affect
• Modulates glutamate, serotonin
and norepinephrine
• Only one randomized controlled trial to
date for agitation
• Side effects include
– Falls
– UTIs
– Diarrhea
– Dizziness
• QTc prolongation
Dextromethorphan-
Quinidine
Considerations

46. • 30mg to 120mg ATC and q2 PRN
• NO DATA AVAILABLE
• Many clinicians, health systems and long-
term care facilities embrace the treatment
• Adverse Reactions
– Respiratory depression
– Stevens-Johnson syndrome
– Anemia, TTP and blood dyscrasias
– Withdrawal symptoms with abrupt withdrawal
– Lethargy and drowsiness
– Nausea, vomiting, and hepatitis
Phenobarbital

47. • Describe the behavior
• Investigate the underlying
contributors/causes
• Create intervention (non-pharmacologic
and pharmacologic)
• Evaluate the intervention’s effectiveness
Summary:
DICE

48. • 61-year-old with Huntington’s Disease who
presents to the hospice inpatient unit (IPU) with
impulsivity and agitation
- Has not slept in two days; is more confused,
pacing, eating food out of garbage
• Patient recently admitted to hospice with
functional decline, falls, weight loss, dysphagia
and worsening behaviors
• Interventions to date: Haldol 5mg every six hours
and every two hours as needed, mirtazapine
30mg at night, sertraline 50mg daily, lorazepam
1mg every six hours and one hour as needed,
amantadine 200mg daily
• Urinalysis and bloodwork were unremarkable.
Patient was transferred to the IPU for further
management of impulsivity and agitation
Case 1:

49. • Describe: Huntington's with impulsivity and
agitation/restlessness
• Investigate: Medication regimen
• Create:
– Discontinue amantadine, mirtazapine and sertraline
– Decrease Haldol 1mg every 6 hours and
Lorazepam 0.5 every 8 hours and PRN
– Start Trazadone 50mg morning and 100mg QHS
and PRN, start Citalopram 10mg twice daily
• Evaluate 1:
– Increase Trazadone 100mg morning and
200mg QHS
– Start dextromethorphan and quinidine
• Evaluate 2:
– Continue current treatment and discharge
home to wife
Case 1:
(Cont.)

50. • 86-year-old with cerebral atherosclerosis with recent
functional decline
- In the past two weeks: bedbound, fall, stage II
sacrum, poor appetite, weight loss, and increased
agitation/aggression
• Daughter took patient out of ALF after patient hit and
tried to bite several staff
- Patient spends most of the day yelling, swearing,
kicking; is very restless in bed
• Comorbidities: hard of hearing, poor vision, arthritis,
peripheral vascular disease, history of stroke,
hypertension, depression, and heart failure
• Bloodwork and urinalysis were unremarkable.
Patient admitted to hospice and transferred to the
IPU for management of vocalizations and
agitation/aggression.
• Medications: sertraline 100mg daily
Case 2:

51. • Describe: Agitation and aggression, including
hitting and biting, worse when patient is
approached, touched or moved
• Investigate: Pain, hearing loss and vision loss
• Create:
–APAP 1,000mg every 6 hours. Corrective
glasses and hearing aids. Speak to patient
before approaching. Trazadone 25mg morning
and 50mg night and PRN, morphine 5mg PRN
• Evaluate 1
–Citalopram 10mg twice daily
–Increase Trazadone 50mg morning and
100mg evening
• Evaluate 2
–Risperidone 0.5mg twice daily
Case 2:
(Cont.)

52. Questions

53. Alzheimer’s Association (2019). Alzheimer’s & Dementia. Retrieved
from https://www.alz.org/alzheimers_disease_facts_%20and
%20_%20figures.asp
Alzheimer’s Association. Facts and Figures (2019). Retrieved from
https://www.alz.org/alzheimers_disease_facts_and_figures.asp.
Antonsdottir, I. M., Smith, J., Keltz, M., & Porstensson, A.P. (2015).
Advancements in the treatment of agitation in Alzheimer’s disease.
Expert Opinionn on Pharmacotherapy, 16(11):1649-1656.
https://doi.org/10.1517/14656566.2015.1059422.
Ayalon. L., Gum, A. M., Feliciano. L, & Arean, P. A. (2006).
Effectiveness of nonpharmacological interventions for the management
of neuropsychiatric symptoms in patients with dementia: a systematic
review. Archives of Internal Medicine, 166(20): 2182-8. doi:
10.1001/archinte.166.20.2182.
Ballard, C.G., et al. (2009). Management of agitation and aggression
associated with Alzheimer’s Disease. Nature Reviews Neurology, 5(5):
245-55. doi: 1038/nrneurol.2009.39
Cohen-Mansfield, J., Thein, K., Marx, M. S. (2014). Predictors of the
impact of non-pharmacologic interventions for agitation in nursing home
residents with advanced dementia. Journal of Clinical Psychiatry,
75(7):e666-671. doi: 10.4088/jcp.13M08649.
References

54. Cummings, J. L., et al. (2015). Effect of Dextromethorphan-Quinidine on
agitation in persons with Alzheimer disease dementia. A randomized
clinical trial. JAMA 314(12): 1242-54. doi: 10.1001/jama.2015.10214.
Gitlin, et al., (2006). A randomized trial of a multicomponent home
intervention to reduce functional difficulties in older adults. Journal of the
American Geriatric Society Society, 54(5): 809-16. doi: 10.1111/j.
1532-5415.2006.00703.x.
Karantzoulis, S., Galvin, J. E. (2011). Distinguishing Alzheimer's
disease from other major forms of dementia. Expert Review of
Neurotherapeutics, 11(11): 1579–91. doi: 10.1586/ern.11.155.
Meehan, K. M., et al. (2002). Comparison of rapidly acting intramuscular
olanzapine, lorazepam, and placebo: A double-blind, randomized study
in acutely agitated patients with dementia. Neuropsychopharmacology,
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Meeks, T. W., & Jeste, D. V. (2008). Beyond the Black Box: What is
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References

55. Mitchell S.L. et al. (2009). The clinical course
of advanced dementia. New England Journal
of Medicine (361)1529-1538. doi:
10.1056/NEJMoa0902234.
Schneider, L. S., et al. (2006). Effectiveness of
atypical antipsychotic drugs in patients with
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doi:10.1056/NEJMoa061240.
References
(Cont.)

56. Evaluation and Management
of Behaviors in Dementia
Joseph W. Shega, MD