1. Rethinking Behavioral Problems Associated with Dementia
Pennsylvania Medical Directors Association
Rethinking Behavioral Problems Associated with Dementia
Joel E. Streim, M.D.
Professor of Psychiatry
University of Pennsylvania
Philadelphia VA Medical Center

2. Overview (of an evolving landscape)
How will the new MDS 3.0 change assessment of behavioral symptoms of dementia?
How can we identify more effective interventions based on an understanding that behaviors are triggered both by
Cognitive deficits due to dementia, as well as
Internal and external factors?
How should we interpret recent research to inform the use of medications to treat behavioral disturbances in dementia?

3. Overview of Changes from MDS 2.0 to MDS 3.0
Revised sections based on pilot studies :
Cognitive Patterns
Delirium
Mood
Behavior
Pain
Gait / falls
Bladder and bowel
Health conditions

4. Minimum Data Set (MDS) Behavior Section
Required completion on admission and at least quarterly
Includes section on behavior problems in NH residents
MDS 2.0 based on staff observations and ratings
MDS 3.0 proposes a shift to the patients’ experience
Patients’ voice in depression assessment
Patients’ perspective / values in behavior assessment

5. Overview of Item Content in Behavior Section of MDS 3.0
CATEGORIES
Psychotic Symptoms
Behavioral Symptoms
Rejection of Care
Wandering
DOMAINS
Presence
Frequency
Alterability
Impact on resident
Impact on others
Change from previous assessment

6. Domains of Behavior in MDS 3.0

7. What makes this behavior a “problem”. Impact on the resident = clin
What makes this behavior a “problem”? Impact on the resident = clin. significant

8. What makes this behavior a “problem”? Impact on Others

9. Rejection of Care: shifting emphasis to resident’s own values and goals

10. E6 - E9. Rejection of Care - Assessment Protocol
Assess whether care rejection behavior is easily addressed or altered by modifying the approach
If not easily addressed or altered, determine whether care rejection behavior interferes with receipt of care that is necessary to meet resident’s (or proxy’s) goals for health and well-being.
Advance healthcare directives
Previously stated goals or preferences
Choices made by proxy on behalf of the resident

11. Wandering: impact and frequency determines whether problematic

12. E11a-b. Wandering - Impact
Does the wandering place the resident at significant risk of getting to a dangerous place?
Stairs, hazmat exposure, risk of getting lost, inadvertant exiting
Does the wandering significantly intrude on the privacy or activities of others?
Interferes with ADLs, leisure activities, or staff restrict programming (group walks, other outings)

13. MDS 3.0 Field Testing and Validation Study
Conducted in
70 community nursing homes (n = 418 residents)
20 VA nursing homes (n = 296 residents)
“Gold standard” nurses administered MDS 3.0
Facility nurses administered MDS 2.0
Cohen-Mansfield Agitation Inventory (CMAI) was gold standard for validation of presence of behavioral symptoms
Neuropsychiatric Inventory (NPI) was gold standard for validation of presence of psychosis

14. Comparison of Kappa Coefficients for MDS 2.0 vs 3.0 and CMAI
Factor 1
0.2278
( )
0.8561
( )
Factor 2
0.3075
( )
0.7250
( )
Factor 3
0.2152
( )
0.3224
( )

15. Factors that cause or contribute to behavioral problems associated with dementia

16. Assessment of behavioral symptoms in patients with dementia
Behavioral symptoms are multiply determined by
Cognitive deficits due to dementia
Internal and external factors
1. How does cognitive impairment lead to behavioral disturbances?
2. What other factors contribute to behavioral disturbances?

17. Cognitive Domains Impaired in Dementia
Syndrome of memory loss (amnesia)
Decline in other cognitive functions
Use of language (aphasia)
Visual-spatial function
Recognition (agnosia)
Performing motor activities (apraxia)
Initiating/executing sequential tasks (abulia, executive dysfunction)

18. How does memory impairment lead to behavioral problems?
Example
Patient is able to dress himself, but can’t remember where his clothes are kept
Walks naked into hallway

19. How does language impairment (aphasia) lead to behavioral problems?
Example
Patient who can’t verbally communicate her dislike of milk
Throws milk carton across the room

20. How does impaired recognition (agnosia) lead to behavioral problems?
Example
Patient can maneuver to pull down his pants, but can’t recognize that a toilet is a receptacle for urination
Urinates on floor near nurses station

21. How does impairment in performance of motor tasks (apraxia) lead to behavioral problems?
Example
Patient is continent of bladder, but cannot unzip or unbutton to pull down her pants
Wets her clothing

22. Apraxia, Disability, and Behavioral Change in Terminal Stages of Dementia
Examples:
Patient no longer holds or manipulates objects (manual apraxia)
Patient sits all day; has difficulty bearing weight and ambulating, even with assistance (gait apraxia)
Patient can swallow, but cannot chew effectively (oral apraxia)

23. What other factors may contribute to behavioral changes in patients with dementia?

24. Common modifiable causes of behavioral disturbances
Unmet needs (physical and psychological)
Environmental / social irritants
Adverse drug effects
Medical conditions / somatic discomfort
Psychiatric conditions

25. Unmet needs that can lead to behavioral disturbances
Physical needs
Nutrition, hydration, toileting, exercise, rest
Psychological needs
Security, autonomy, affection, self-worth

26. Environmental irritants that can lead to behavioral disturbances
Physical
Noise
Confusing visual stimuli
Uncomfortable temperature
Unfamiliar surroundings
Social
Changes in routines
Provocative social interactions

27. Adverse drug effects that can cause behavioral disturbances
Nuisance symptoms
Anticholinergic effects
Antihistaminic effects
Paradoxical excitation / disinhibition
Intoxication or withdrawal states
Akathisia

28. Medical conditions and somatic discomfort that can lead to behavioral disturbances
Arthritis
Dehydration
Prostatic hypertrophy
COPD
Cerebrovascular disease
CHF
Somatic discomfort
Pain
Constipation
Urinary urgency
Shortness of breath
Dizziness
Fatigue

29. Psychiatric conditions that can cause behavioral disturbances
Delirium
Depression
Anxiety
Psychosis

30. Psychotic symptoms and agitation in dementia
10% to 73% have delusions
21% to 49% have hallucinations
Visual hallucinations characteristic in Lewy Body dementia
Sensory deprivation increases risk
60% to 75% exhibit agitated behavior
Finkel. J Clin Psychiatry. 2001;62(suppl 21):3.
Cohen-Mansfield and Billig. J Am Geriatr Soc. 1986;34:711.

31. So… if the patient has dementia with agitated behaviors associated with psychosis, is it appropriate to use antipsychotic medication in 2008?

32. Prior Evidence for Efficacy and Safety of Antipsychotic Drugs
Meta-analyses of conventional antipsychotic drug studies found significant efficacy, but small effect sizes (Schneider et al, 1990)
Efficacy studies of atypical antipsychotic drugs showed drug significantly better than placebo for psychosis, agitation, aggression (Katz et al 1999, Street 2000, Mintzer 2008)
Atypical antipsychotics associated with less Parkinsonism; but sedation, gait disturbance and falls occur at higher doses

33. Regulatory Interpretation of Risks
FDA warning about risk of diabetes (Sept. 2003)
Applies to the class for all ages, conditions
FDA warnings about CVAEs (April 2003, Jan. 2004, March 2005)
applies to risperidone, olanzapine, and aripiprazole in elders with dementia
FDA advisories about mortality (April 2005, June 2008)
applies to atypical AND conventional antipsychotics in dementia
Includes a reminder that these drugs are not FDA-approved for this indication

34. Risk of Cerebrovascular Adverse Events (CVAEs) in Elderly Patients With Dementia
# of trials
CVAEs
Numbers Needed to Harm
Active drug
Placebo
Risperidone 4
3.8% (29/764)
1.5% (7/466) 44
Olanzapine 5
1.3% (15/1178)
0.4% (2/478)
118
Aripiprazole 3
1.3% (8/595)
0.6% (2/343)
112
In US, letters to healthcare professionals were sent and warning added in prescribing information
UK Committee on Safety of Medicines guideline:
Avoid use in BPSD of dementia
Limited to short-term and under-specialist advice for the management of acute psychotic conditions with risperidone
Consider risk in treating patients with previous history of stroke or transient ischemic attack and assess cerebrovascular disease risk factors including hypertension, diabetes, smoking, and atrial fibrillation
In 2 separate Health Canada Advisories, pooled analyses of 4 placebo-controlled trials of risperidone in dementia with 1230 patients and 5 placebo-controlled trials of olanzapine in dementia with 1662 patients demonstrated an increased risk of CVAEs with risperidone and olanzapine compared with placebo. Data from the advisory letters are presented on the slide.1,2
In response to these findings, letters to US healthcare providers were sent and changes in the prescribing information of olanzapine and risperidone were made to include a warning on the increased risk as well as reminding clinicians that these agents are not approved for use in patients with dementia-related psychosis.3,4
In the UK, the Committee on Safety of Medicines advised that risperidone and olanzapine should not be used for treatment of BPSD and that the use of risperidone for acute psychotic conditions in elderly should be limited to the short term and under specialist advice.5 Further, in patients with a previous history of stroke or transient ischemic attack, risk of cerebrovascular events should be carefully considered including risk factors such as hypertension, diabetes, current smoking, and atrial fibrillation.
References: 1. Health Canada Advisory for Health Professionals. Risperdal® (risperidone) and cerebrovascular adverse events in placebo-controlled dementia trials. October 11, Available at: Accessed May 26, 2004; 2. Health Canada Advisory for Health Professionals. Zyprexa® (olanzapine) and cerebrovascular adverse events in placebo-controlled elderly dementia trials. March 10, Available at: Accessed May 26, 2004; 3. Risperdal® (risperidone) [package insert]. Titusville, NJ: Janssen Pharmaceutica Products, LP; 2003; 4. Zyprexa® (olanzapine) [package insert]. Indianapolis, Ind: Eli Lilly and Company; 2004; 5. Committee on Safety of Medicines. Atypical antipsychotic drugs and stroke. Available at: Accessed March 31, 2004.
Health Canada Advisory for Health Professionals. Available at: dpt/risperdal1_e.html and Accessed May 26, 2004; Committee on Safety of Medicines. Available at: Accessed March 31, 2004.

35. Cerebrovascular Adverse Events: Pooled Analyses of Dementia RCTs
Sample Size CVAEs Exposure RR (95% CI) subject-yrs
(drug/PBO) (drug/PB0) (drug/PBO)
Risperidone / / / ( )
Olanzapine / / / ( )
Aripiprazole / / / ( )
Quetiapine / / / ( )
Ziprasodone no available clinical trials data in dementia patients
Haloperidol ( )
Re-order this way OL
RIS
ARP
QUE
ZIP
NB: 95% CI includes 1 for nearly all drugs studied !!
Adapted from Schneider L. Paper presented at Annual Meeting of the American Association for Geriatric Psychiatry, San Diego CA, March 5, 2005.

36. Mortality in Dementia Trials: Meta-analysis of RCTs
Schneider examined 15 randomized, placebo-controlled trials
6 were published
Most were weeks duration
Sample
3353 patients randomized to atypical antipsychotics
1757 patients randomized to placebo
Death rates
3.5% in treatment group
2.3% in control group
Risk difference = 0.01
95% Confidence Interval, (P=.01)
Schneider LS, et al. JAMA 2005, 294:

37. Relative Risk of Death: Conventional vs. Atypical Antipsychotics
Model Hazard Ratio (95% CI)
Unadjusted analysis ( )
Adjusted analysis*
Use of any conventional APM ( )
Low dose of conventional APM (<median) ( )
High dose of conventional APM (>median) ( )
Adjusted analysis of death**
<40 days after beginning therapy ( )
40-79 days after beginning therapy ( )
days after beginning therapy ( )
Adjusted analysis of patient subgroups**
With dementia ( )
Without dementia ( )
In a nursing home ( )
Not in a nursing home ( )
*APM=antipsychotic medication CI=confidence interval
**Hazard ratios adjusted for age, sex, cardiovascular and cerebrovascular disease, psychiatric disorders, other medications used, and residential status.
Wang P et al. N Engl J Med. 2005;353:

38. Deaths per person-year Days after initiation of medicine
Risk of Death in Elderly Patients: Atypical vs Conventional Antipsychotics
0.6
Conventional antipsychotics
Atypical antipsychotics
0.5
0.4
Deaths per person-year
0.3
0.2
0.1 20 40 60 80
100
120
140
160
180
Days after initiation of medicine
Wang P et al. N Engl J Med. 2005;353:

39. CATIE-AD: Effectiveness of Atypical Antipsychotic Drugs in Outpatients with Alzheimer’s Disease
42-site, double blind, RCT
N=421 patients with AD + psychosis, agitation or aggression
Randomized to
Olanzapine (mean dose 5.5 mg/d)
Quetiapine (mean dose 56.5 mg/d)
Risperidone (mean dose 1.0 mg/d)
Placebo
Primary outcomes:
Time to all-cause discontinuation
Number of patients with at least minimal improvement on CGIC at 12 weeks
Schneider LS et al. N Engl J Med 2006;355:

40. CATIE-AD: Primary Outcomes
No significant differences among groups on CGIC (P=0.22)
No significant differences in time to discontinuation for any reason (P=0.52)
Schneider LS et al. N Engl J Med 2006;355:

41. CATIE-AD: Summary of Results
Time to discontinuation due to lack of efficacy favored olanzapine and risperidone (P=0.002)
Time to discontinuation due to adverse events or intolerability favored placebo (P=0.009)
Schneider LS et al. N Engl J Med 2006;355:

42. CATIE AD: Conclusions
Atypical antipsychotic drugs appear more efficacious than placebo, but…
Adverse events limit overall effectiveness
Use may be appropriate for patients who have no or few adverse effects, and for whom benefits can be discerned
Schneider LS. Presented at Annual Meeting of the AAGP, March 2, 2007, New Orleans LA.

43. Incorporating Risk Tolerance in Making Treatment Decisions
When is the balance between expected benefits and known risks acceptable to the patient or surrogate decision-maker?

44. Documentation is Crucial
Inform patient or proxy of benefits and risks
Discuss acceptability of treatment
Document discussion, including concurrence with treatment plan

45. Summary MDS 3.0 Behavior items
Perform better than MDS 2.0 at detecting presence of target behaviors
Clarify when behaviors are problems
Respect resident values and preferences
Behavioral symptoms in dementia may be explained by
Deficits in various cognitive domains
Other factors such as unmet needs, environmental irritants, drug effects, medical and psychiatric conditions

46. Summary
Antipsychotic drugs may benefit selected nursing home residents, but it is advisable to:
Discuss risks, including stroke and death
Document that balance between expected benefits and known risks is acceptable to patient or proxy

47. Questions ???