Post on 27-Mar-2015
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
Edwards, et al: Clin Drug Invest 2005; 125(8) 507-515
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
Edwards, et al: Clin Drug Invest 2005; 125(8) 507-515
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
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
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
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))
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
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)
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
► 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
SummarySummary