Severe Alzheimers Disease in the Institutional Setting: Treatment Challenges, Behavioral Issues, and...

Severe Alzheimer’s Disease in the Severe Alzheimer’s Disease in the Institutional Setting:Institutional Setting:

Treatment Challenges, Behavioral Issues, Treatment Challenges, Behavioral Issues, and Pharmacologic Management Strategies and Pharmacologic Management Strategies

Focus on Patients in the Assisted and Skilled Focus on Patients in the Assisted and Skilled Nursing EnvironmentNursing Environment

Session HighlightsSession Highlights

► Focus on institutionalized patients, mainly skilled Focus on institutionalized patients, mainly skilled nursing facilitiesnursing facilities

► Review demographics, and physical and psychiatric co-Review demographics, and physical and psychiatric co-morbiditiesmorbidities

► Discuss disease characteristics and stagingDiscuss disease characteristics and staging

► Determine critical management issues for caregiversDetermine critical management issues for caregivers

► Discuss clinical and pharmacoeconomic benefits of Discuss clinical and pharmacoeconomic benefits of treatmenttreatment

Payor status Mostly private and Mostly Medicaid, privateThird party. Some waiver minimal third partyMedicaid

Physicians Multiple PCPs Medical Directors andFew key attending

Caregivers Family Nursing staff

AD stage Early to moderate Moderate to severe

Comorbidities Moderate Multiple

Functional Status Slight to moderately impaired Moderately to severely

impaired

Goals Improve and maintain cognition Maintain ADLs

Slow decline Slow declineSlow behavior emergence Control behaviorsCost Savings: Cost Savings: Delay admission “age in place” Reduced staff time

ALF ALF SNFSNF

Characteristics of ALF vs. SNFCharacteristics of ALF vs. SNF

Dementia Prevalence in PrimaryDementia Prevalence in Primaryand Long-Term Care Settingsand Long-Term Care Settings

► 75% of patients with moderate to severe 75% of patients with moderate to severe dementia may go undiagnosed in the dementia may go undiagnosed in the primary care settingprimary care setting

► Almost 50% of residents admitted to long-Almost 50% of residents admitted to long-term care (LTC) facilities have some term care (LTC) facilities have some degree of dementiadegree of dementia

► Up to three quarters of nursing home Up to three quarters of nursing home residents have dementiaresidents have dementia

Magaziner J, et al. Gerontologist. 2000;40:663-672. Callahan CM, et al. Ann Intern Med. 1995;122:422-429.

MDS Cognitive PerformanceMDS Cognitive PerformanceScale (CPS)Scale (CPS)

► Derived from five questions directly from Derived from five questions directly from the Minimum Data Set (MDS)the Minimum Data Set (MDS)

► Validated as an accurate screening Validated as an accurate screening instrument in the skilled facility population instrument in the skilled facility population in the geriatric literaturein the geriatric literature

► Positive correlation to the Mini Mental Positive correlation to the Mini Mental Status Exam (MMSE)Status Exam (MMSE)

Morris JN, et al. MDS Cognitive Performance Scale. J Gerontol. 1994; 40:M172-M182.

Cognitive Performance ScaleCognitive Performance Scale

► Comatose [MDS B1] Comatose [MDS B1] 0 - no,0 - no, 1 - yes1 - yes

► Short Term Memory OK [MDS B2a]Short Term Memory OK [MDS B2a] 0 - memory okay0 - memory okay 1 - memory problem1 - memory problem

► Cognitive Skills for Daily Decision Making [MDS B4]Cognitive Skills for Daily Decision Making [MDS B4] independentindependent modified independencemodified independence moderately impairedmoderately impaired severely impairedseverely impaired

Cognitive Performance Scale (CPS)Cognitive Performance Scale (CPS)

► Communication/Hearing Patterns [C4]Communication/Hearing Patterns [C4] 0 - understood0 - understood 1 - usually understood1 - usually understood 2 - sometimes understood2 - sometimes understood 3 - rarely/never understood3 - rarely/never understood

► Eating [MDS G1h]Eating [MDS G1h] 0 - independent0 - independent 1 - supervision1 - supervision 2 - limited assistance2 - limited assistance 3 - extensive assistance3 - extensive assistance 4 - total dependence4 - total dependence

Cognitive Performance Scale (CPS) Scoring System & Cognitive Performance Scale (CPS) Scoring System & Correlating Mini Mental Status Exam (MMSE) ScoreCorrelating Mini Mental Status Exam (MMSE) Score

► CPS SCORECPS SCORE 0 - Intact0 - Intact 1 - Borderline Intact1 - Borderline Intact 2 - Mild Impairment2 - Mild Impairment 3 - Moderate 3 - Moderate

ImpairmentImpairment 4 - Moderately 4 - Moderately

Severe Imp.Severe Imp. 5 - Severe 5 - Severe

ImpairmentImpairment 6 - Very Severe 6 - Very Severe

ImpairmentImpairment

► MMSE SCORE (avg.)MMSE SCORE (avg.) 24.924.9 21.921.9 19.219.2 15.415.4 6.96.9 5.15.1 0.40.4

Morris JN, et al. MDS Cognitive Performance Scale. J Gerontol. 1994;40: M172-M182.

Prevalence of Selected CNS ConditionsPrevalence of Selected CNS Conditionsfrom Admission MDS Filesfrom Admission MDS Files

0 20 40 60 80 100Percentage

Alzheimer’s

Dementia other than AD

Schizophrenia

Delusions/Hallucinations

CognitiveImpairment

(CPS)

None of the above

9.3%

20.9%

1.4%

1.4%

27.1%

40.0%

(N = 6,894 Residents)(N = 6,894 Residents)(N = 6,894 Residents)(N = 6,894 Residents)

Admission Cognitive Status of All ResidentsAdmission Cognitive Status of All Residentswith Dementia (MDS Diagnosis or CPS with Dementia (MDS Diagnosis or CPS >> 2) 2)

17.8

76.8

5.30

102030405060708090

0-1 2-4 5-6

MDS CPS Score

Per

cen

tag

e

AIT Use in Residents with Admission AIT Use in Residents with Admission Dementia (MDS Diagnosis or CPS Dementia (MDS Diagnosis or CPS >> 2) 2)

3.83.6

5.2

0

1

2

3

4

5

6

0-1 2-4 5-6

MDS CPS Score

Per

cen

tag

e

Pharmacologic TreatmentPharmacologic TreatmentSuccess in ADSuccess in AD

Treatment success may currently be defined as:

Untreated/natural course

Stabilization

Improvement

Less-than expected decline

Time

Progression of Disease

ChangeFrom

Baseline

Galasko. Eur J Neurol. 1998;5(suppl 4):S9-S17.

Act

ivit

ies

of

Dai

ly

Liv

ing

(A

DL

s)

Progressive Loss of FunctionMMSE Score

Keep appointmentsTelephone

Obtain meal/snackTravel alone

Use home appliancesFind belongings

Select clothesDress

Groom

25 20 15 10 5 0

0 2 4 6 8 10Years

Maintain hobbyDispose litter

Clear tableWalk

Eat

Functional Loss Over the Course of ADFunctional Loss Over the Course of AD

Benefits of Persistent Treatment:Benefits of Persistent Treatment:Delay in Nursing Home PlacementDelay in Nursing Home Placement

Geldmacher DS, et al. J Am Geriatr Soc. 2003;51(5 Suppl Dementia):S289-S295.

Median Time to First Dementia-Related NH Placement

MonthsMonths

Maximum donepezil exposure (n=310) 66.1

Limited donepezil exposure (n=113) 44.721.4

monthdelay

0 10 20 30 40 50 60 70

Persistent treatment with donepezil may have delayed time to 1st dementia-related NH placement by nearly 2 years

Benefits of Treating Moderate to Benefits of Treating Moderate to Severe AD Domains of EfficacySevere AD Domains of Efficacy

Behavior

Function

Cognition

Physical and Psycho-social

Well-being

Reduced caregiverburden

Pharmaco-economic

benefit

ReducedBehaviors

CMS GOAL

► Restore functional capacity, and slow decline

► Reduce severity of behaviors

► Reduce and forestall new use of psychotropic agents

► Realize pharmacoeconomic benefits from

• Reduction in behaviors and behavior medications

• Reduction in care giver burden

• Reduction in acuity of co-morbidities

Goals for Moderately Severeto Severe Patients

Psychiatric Medicine Consensus ReportsAlzheimer’s Disease: Risk Stratification, Patient Evaluation, and Outcome-Effective Pharmacologic Therapy, Year 2004 Clinical Update

Donepezil Effects on ADLsDonepezil Effects on ADLs& Caregiver Burden& Caregiver Burden

► Feldman et al, JAGS 2003

Community dwelling and ALF AD patientsN=290, MMSE range 5-17Measurements by

● Disability Assessment for Dementia Scale (DAD)

● Modified Instrumental Activities of Daily Living Scale (IADL+)

● Modified Physical Self Maintenance Scale (PSMS+)

Feldman H, et al. J Am Geriatr Soc. 2003;51:737-744.

Caregivers Spent Less TimeCaregivers Spent Less TimeAssisting Patients With ADLsAssisting Patients With ADLs

Feldman H, et al. Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer’s disease and the effect on caregiver burden. J Am Geriatr Soc. 2003;51:737-744.

Behaviors Are CostlyBehaviors Are Costly

The costs of behavioral management for AD patients is The costs of behavioral management for AD patients is significantsignificant

► Kleinman, et al Behaviors due to dementia, psychosis,

agitation/aggression and depression ‘cost’ $5.23 per occurance in intervention and documentation

Based on staff mix, frequency, and median US wages (2001), behavioral management ‘costs’ between $75 and $344 PER PATIENT PER MONTH

► Beeri, et al 30% of the total annual cost of caring for an AD patient is

invested in behavioral management

Kleinman, et al: Consult Pharm 2002; 17:497-507

Beeri, et al: Int J Geriatri Psychiatry 2002; 17:403-408

Rivastigmine Effects on BehaviorRivastigmine Effects on Behavior

Edwards, et al

► Nursing Home AD patients

► 26 week open label prospective study, with 26 week open label extension

► N=173, MMSE range 6-15

► Neuropsychiatric Inventory, Nursing Home Version (NPI-NH)

► 85% of patients receiving therapeutic doses at study end (6-12mg/day)

Edwards, et al: Clin Drug Invest 2005; 125(8) 507-515

Rivastigmine Effects onRivastigmine Effects onBehavior BaselineBehavior Baseline


62%

56%52%

38%

32%

11%

6%

0%

10%

20%

30%

40%

50%

60%

70%

%

Therapuetic category

% o

f p

atie

nts

any psychotropic agent

antidepressants

antipsychotic agent

no treatment

anxiolytic agent

hypnotics

mood stabilizers

0%

10%

20%

30%

40%

50%

60%

70%

80%

Therapuetic category

% r

edu

ced

or

dis

con

tin

ued

any psychotropic agent

antidepressants

antipsychotic agent

no treatment

anxiolytic agent

hypnotics

mood stabilizers

Rivastigmine Effects on BehaviorRivastigmine Effects on Behavior52 Week Endpoint52 Week Endpoint


n=43

n=36

n=62

n=55

n=36

n=72

Rivastigmine Effects on BehaviorRivastigmine Effects on Behavior

► 15% of patients increased their dose of any psychotropic

► 11% of those on an antipsychotic

► 15% of those on an antidepressant

► 3% of those on an anxiolytic

► 8% of those on a hypnotic

► 2% of patients receiving no psychotropic started one

Percentage of patients taking psychotropic medication during rivastigmine treatment

Psychotropic medication use at baseine (n=100)

Increased dose

%

Reduced dose

%

Terminated medication

%

No Change

%

Antipsychotics

(n=55) 7 13 31 49

Anxiolytics

(n=33) 9 18 21

52

Antidepressants

(n=57) 5 19 16 60

Rivastigmine Rivastigmine & Behavior: Psychotropic& Behavior: PsychotropicMedication Use in Nursing Home AD PatientsMedication Use in Nursing Home AD Patients

Edwards KR, et al. In: Proceedings of the US Psych and Mental Health Congress. 1999.

Galantamine in Advanced DiseaseGalantamine in Advanced Disease

Blesa, et al:

► Post hoc pooled data study of 4 phase III registration trials

► 6 month placebo-controlled double blind randomized studies with 6 month open label extensions: consistent study design validates pooling

► Group 1 (N=72) MMSE<12, galantamine 24mg/day vs placebo.

► Group 2 (N=165) ADAS-Cog>30, galantamine 24mg/day vs placebo)

Blesa, R., et al: Dement Geriatr Cogn Disorder 2003; 15:79-87

Galantamine in Advanced DiseaseGalantamine in Advanced Disease

Blesa, R., et al: Dement Geriatr Cogn Disorder 2003; 15:79-87

Donepezil in Advanced DiseaseDonepezil in Advanced Disease

Winblad, et al:

► Swedish nursing home AD patients(DSM-IV)

► 26 week, randomized, double-blind, placebo controlled study

► N=194, MMSE=1-10

► Severe Impairment Battery (SIB)

► Alzheimer’s Disease Cooperative Study –Activities of Daily Living-severe (ADCS-ADL-sev)

► Randomized to 5mg/daily x 4 weeks then option to increase to 10mg/daily, vs placebo

► Mean donepezil dose was 8.2mg/day; 91% reached 10mg/day

Winblad, et al: Donepezil in Patients with Severe Alzheimer’s Disease: doubleblind, parallelt-group, placebo-controlled study. The Lancet 2006:367:1057-1065

Winblad, et al:

► Donepezil group improved on SIB Mean improvement of 5.7 (95% CI 1.5-9.8)

p=0.008 Placebo group mean decline of 1.8

► Donepezil group declined less on ADCS-ADL-severe Mean of decline of 1.7 (95% CI 0.2-3.2)

p=0.03 Placebo group mean decline of 2.9

Winblad, et al: Donepezil in Patients with Severe Alzheimer’s Disease: doubleblind, parallelt-group, placebo-controlled study. The Lancet 2006:367:1057-1065

Donepezil in Advanced DiseaseDonepezil in Advanced Disease

““Memantine in Moderate toMemantine in Moderate to

Severe Alzheimer’s Disease”Severe Alzheimer’s Disease”

““Memantine in Moderate toMemantine in Moderate to

Severe Alzheimer’s Disease”Severe Alzheimer’s Disease”

Reisberg B et al.Reisberg B et al.

N Engl J MedN Engl J Med. 2003;348:1333-1341. 2003;348:1333-1341

Reisberg B et al.Reisberg B et al.

N Engl J MedN Engl J Med. 2003;348:1333-1341. 2003;348:1333-1341

Study DesignStudy Design

DesignDesign

► Phase 3, multicenter (32; US), randomized, double-Phase 3, multicenter (32; US), randomized, double-blind, placebo-controlled studyblind, placebo-controlled study

Population Population

► 252 outpatients with moderate to severe AD 252 outpatients with moderate to severe AD (MMSE range, 3-14)(MMSE range, 3-14)

TreatmentTreatment

► Memantine 20 mg/day (10 mg bid) 4-week titration Memantine 20 mg/day (10 mg bid) 4-week titration (5(510 10 15 15 20 mg) 20 mg)

DurationDuration

► 28 weeks + 24-week open-label extension*28 weeks + 24-week open-label extension*

Reisberg B et al. Reisberg B et al. N Engl J MedN Engl J Med. 2003;348:133301341. 2003;348:133301341

Ferris S et al. Presented at the 16Ferris S et al. Presented at the 16thth Annual Meeting of the American Association for Annual Meeting of the American Association for Geriatric Psychiatry; March 1-4, 2003; Honolulu, HIGeriatric Psychiatry; March 1-4, 2003; Honolulu, HI

Reisberg B et al. Reisberg B et al. N Engl J MedN Engl J Med. 2003;348:133301341. 2003;348:133301341

Ferris S et al. Presented at the 16Ferris S et al. Presented at the 16thth Annual Meeting of the American Association for Annual Meeting of the American Association for Geriatric Psychiatry; March 1-4, 2003; Honolulu, HIGeriatric Psychiatry; March 1-4, 2003; Honolulu, HI

Outcome MeasuresOutcome Measures

Primary Efficacy VariablesPrimary Efficacy Variables

► GlobalGlobal CIBC-PlusCIBC-Plus► FunctionalFunctional ADCS-ADLADCS-ADL1919

inventoryinventory(modified 19 item) (modified 19 item)

Reisberg B et al. Reisberg B et al. N Engl J MedN Engl J Med. 2003;348:133301341. 2003;348:133301341Reisberg B et al. Reisberg B et al. N Engl J MedN Engl J Med. 2003;348:133301341. 2003;348:133301341

Memantine/Donepezil Dual Therapy Is Memantine/Donepezil Dual Therapy Is Superior to Placebo/Donepezil Therapy for Superior to Placebo/Donepezil Therapy for

Treatment of Moderate to Severe Treatment of Moderate to Severe Alzheimer’s DiseaseAlzheimer’s Disease

Memantine/Donepezil Dual Therapy Is Memantine/Donepezil Dual Therapy Is Superior to Placebo/Donepezil Therapy for Superior to Placebo/Donepezil Therapy for

Treatment of Moderate to Severe Treatment of Moderate to Severe Alzheimer’s DiseaseAlzheimer’s Disease

Tariot P et al.Tariot P et al.

J Am Geriatr Soc.J Am Geriatr Soc. 2003;51(S4):S225-S226 2003;51(S4):S225-S226

Tariot P et al.Tariot P et al.

J Am Geriatr Soc.J Am Geriatr Soc. 2003;51(S4):S225-S226 2003;51(S4):S225-S226

Study DesignStudy Design

► Randomized, double-blind, placebo-controlled, Randomized, double-blind, placebo-controlled, parallel group studyparallel group study

► 1-2 to 2-week single-blind placebo lead-in1-2 to 2-week single-blind placebo lead-in

► 24-week double-blind treatment24-week double-blind treatment

► Memantine 20 mg/day (10 mg bid), titrated over a Memantine 20 mg/day (10 mg bid), titrated over a 4-week period, or placebo, combined with stable 4-week period, or placebo, combined with stable doses of donepezildoses of donepezil

► 37 investigator sites in the United States37 investigator sites in the United States

Tariot P et al. Tariot P et al. J Am Geriatr SocJ Am Geriatr Soc. 2003;51(S4):S225-S226. 2003;51(S4):S225-S226Tariot P et al. Tariot P et al. J Am Geriatr SocJ Am Geriatr Soc. 2003;51(S4):S225-S226. 2003;51(S4):S225-S226

Entrance CriteriaEntrance Criteria

► Diagnosis of probable AD consistent with Diagnosis of probable AD consistent with NINCDS-ADRDA criteriaNINCDS-ADRDA criteria

► MRI or CT scan consistent with probable ADMRI or CT scan consistent with probable AD

► MMSE scores of 5 to 14 at screening and baselineMMSE scores of 5 to 14 at screening and baseline

► Donepezil monotherapy for >6 months prior to Donepezil monotherapy for >6 months prior to entrance and at stable doses (5 to 10 mg/day) for entrance and at stable doses (5 to 10 mg/day) for the 3 months preceding and throughout the study the 3 months preceding and throughout the study period period


Functional Efficacy AssessmentFunctional Efficacy Assessment

Alzheimer’s Disease Cooperative Study-Alzheimer’s Disease Cooperative Study-Activities of Daily Living modified 19 - item Activities of Daily Living modified 19 - item inventory (ADCS-ADLinventory (ADCS-ADL1919))


Secondary Functional Secondary Functional

Efficacy AssessmentsEfficacy Assessments► GlobalGlobal

-- Clinician’s Interview-Based Impression Clinician’s Interview-Based Impression of of Change plus caregiver input (CIBIC-Change plus caregiver input (CIBIC-Plus)Plus)

► FunctionFunction

-- Behavioral Rating Scale for Geriatric Behavioral Rating Scale for Geriatric Patients—care dependency subscale Patients—care dependency subscale (BGP-(BGP- Care)Care)


► Treatment for early to moderate stage ALF AD patients focuses Treatment for early to moderate stage ALF AD patients focuses on improving and maintaining cognition, maintaining ADLs, on improving and maintaining cognition, maintaining ADLs, and slowing emergence of behaviors. Cost savings are and slowing emergence of behaviors. Cost savings are associated with delayed nursing home admission.associated with delayed nursing home admission.

► Treatment for moderate to severe stage NF patients focuses on Treatment for moderate to severe stage NF patients focuses on maintaining ADLs and slowing functional decline, and maintaining ADLs and slowing functional decline, and controlling behaviors. Cost savings are associated with controlling behaviors. Cost savings are associated with reduced staff time, reduced psychotropic use.reduced staff time, reduced psychotropic use.

► Moderate and Severe stage AD patients in all setting benefit Moderate and Severe stage AD patients in all setting benefit from persistent treatment with cholinesterase inhibitors, and/or from persistent treatment with cholinesterase inhibitors, and/or NMDA receptor antagonistsNMDA receptor antagonists

► Benefits are both clinically significant for patients, and Benefits are both clinically significant for patients, and economically significant for care givers and healthcare economically significant for care givers and healthcare systemssystems

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Severe Alzheimers Disease in the Institutional Setting: Treatment Challenges, Behavioral Issues, and...

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