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Why Physicians Do NotWhy Physicians Do NotDiagnose Alzheimer’s DiseaseDiagnose Alzheimer’s Disease
Mark A. Sager, MDMark A. Sager, MDProfessor of Medicine and Population Health Sciences
Director, Wisconsin Alzheimer’s Institute
University of Wisconsin Medical School
WISCONSIN ALZHEIMER’S INSTITUTE
Age
CognitiveFunction
248
Death
MCI
AD syndrome
Normal aging
Interventions
Diagnosing Alzheimer’s Disease
• Almost 50% of persons with dementia are never diagnosed or treated
• Most persons who are treated for dementia are treated inappropriately
WISCONSIN ALZHEIMER’S INSTITUTE
Underrecognition of Cognitive Impairment in Assisted Living Facilities
• 230 ALF residents in 7 facilities in Nebraska
• Not dementia-specific
• Defined cognitive impairment as <24 on the MMSE
WISCONSIN ALZHEIMER’S INSTITUTE
JAGS, 2005
Underrecognition of Cognitive Impairmentin Assisted Living Facilities
WISCONSIN ALZHEIMER’S INSTITUTE
353JAGS, 2005
63%
37%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Per
cen
tag
e
MMSE < 24MMSE ≥ 24
Underrecognition of Cognitive Impairmentin Assisted Living Facilities
WISCONSIN ALZHEIMER’S INSTITUTE
354JAGS, 2005
75%
22%
11%
63%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Per
cen
tag
e
No diagnosis No treatment Self-medicate Surrogate decision-maker
For persons with For persons with MMSE < 24 (N=145)MMSE < 24 (N=145)
Prevalence of Undetected MCI – Study Population
Mean age (yrs) 76
Female (%) 58
Education (yrs) 16
Mean MMSE 28
Source: Hermann, Sager 2002
WISCONSIN ALZHEIMER’S INSTITUTE
17
Prevalence of Undetected MCI
N (%)
Undetected dementia (n = 200) 21 (11)
Undetected MCI (n = 179) 18 (10)
Rate of undetected impairment 39 (20)
Source: Hermann, Sager 2002
WISCONSIN ALZHEIMER’S INSTITUTE
Interest in Screening andTreatment for MCI
WISCONSIN ALZHEIMER’S INSTITUTE
• Questions from Alzheimer’s Association website “fact sheet”
• N= 149
• 71% over age 65
Dale et al JAGS, 2006
WISCONSIN ALZHEIMER’S INSTITUTE
Would you want to be tested for memory problems as part of a routine medical exam?
Yes 80 %
Interest in Screening andTreatment for MCI
Dale et al JAGS, 2006
WISCONSIN ALZHEIMER’S INSTITUTE
Would you want to know as early as possible that you had Alzheimer’s Disease?
Yes 92%
Interest in Screening andTreatment for MCI
Dale et al JAGS, 2006
Interest in Screening and Treatmentfor MCI - Conclusion
WISCONSIN ALZHEIMER’S INSTITUTE
“Older adults expressed high interest in screening and treatment for MCI. Such high interest is potentially troubling…”
Dale et al JAGS, 2006
Reasons for High Rate ofUndiagnosed Cases of Dementia
• Reliance on family
• Subtlety of early symptoms
• Low priority given by MD’s
WISCONSIN ALZHEIMER’S INSTITUTE
Why Physicians Do Not Diagnoseand Treat Alzheimer’s Disease
Deficiencies in Current Knowledge
Practice Obstacles
Uncertainties
Avoidance Behavior and Skepticism
Plus
Create
Which lead to
WISCONSIN ALZHEIMER’S INSTITUTE
Potential Benefits of Treatment with AcetylCholinesterase Inhibitors
• Slow cognitive decline
• Delay emergence of behavioral symptoms
• Slow functional decline
• Reduce caregiver stress
• Delay nursing home placement
WISCONSIN ALZHEIMER’S INSTITUTE
-4
-3
-2
-1
0
1
2
3
4
5
6
70 1 3 6 9 12
Galantamine 24 mgPlaceboGalantamine 24 mg
Galantamine Long-term Cognitive Function Over 12 Months
Improvement
DeteriorationMea
n C
hang
e in
AD
AS
-cog
fro
m
Bas
elin
e
Time (months) Raskind, MA, et al. Neurology 54:2261-2268; 2000.
=P<0.05
Double-blind Open-extension
WISCONSIN ALZHEIMER’S INSTITUTE
58
Alteration of Clinical Outcomes in the NaturalHistory of AD by Cholinesterase Inhibitors
WISCONSIN ALZHEIMER’S INSTITUTE
• University of Pittsburgh ADRC
• 270 patients with AD; 135 CEI and 135 no-CEI
• Matched for age, education, MMSE, duration of dementia
Lopez, et al., JAGS, 2005
WISCONSIN ALZHEIMER’S INSTITUTE
• Average mean change in MMSE/yr was 3.8 points ± 4.2 for 1,139 AD patients in ADRC
• Classified study patients as slow progressors (≤ 2 change in MMSE/yr and rapid progressors (≥ 3 change in MMSE/yr)
• Mean age 73, mean MMSE 19, mean education 12.5 years
Lopez, et al., JAGS, 2005
Alteration of Clinical Outcomes in the NaturalHistory of AD by Cholinesterase Inhibitors
Effect of CEI Treatment on AD Progression
WISCONSIN ALZHEIMER’S INSTITUTE
0%10%20%30%40%50%60%70%80%90%
100%
Treated Not Treated
Pe
rce
nta
ge
Slow ProgressionRapid Progression
RR=2.45 (1.45-4.16), p=.001
Lopez et al., 2005
N=81 N=82
N=54 N=53
60%
40% 39%
61%
Effect of CEI Treatment on Risk of Nursing Home Placement
WISCONSIN ALZHEIMER’S INSTITUTE
Lopez et al., 2005
0%10%20%30%40%50%
60%70%80%90%
100%
After 2 yrs After 3 yrs
Pe
rce
nta
ge
TreatmentNo Treatment
1% 11% 11%
50%
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 100 200 300 400 500 600 700 800 900
Probability of Remaining at HomeP
rob
abil
ity
of
Rem
ain
ing
at
Ho
me
Time (Days)
Tacrine Dose (mg/day)
< 80
> 80 < 120
> 120 < 160
WISCONSIN ALZHEIMER’S INSTITUTE
Knopman D, et al. Neurology 47:166-167; 1996
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 100 200 300 400 500 600 700 800 900
Probability of SurvivalP
rob
abili
ty o
f S
urv
iva
l
Time (Days)
Tacrine Dose (mg/day)
< 80
> 80 < 120
> 120 < 160
WISCONSIN ALZHEIMER’S INSTITUTE
91Knopman D, et al. Neurology 47:166-167; 1996
WISCONSIN ALZHEIMER’S INSTITUTE
Caregiver Interventions to Reduce NursingHome Placement of Patients with AD
• RCT of 406 caregiver spouses, 1987-1997
• New York University
• Required treatment group to attend support groups (58%)
• Allowed control group to attend support groups (42%)
Neurology, 2006
WISCONSIN ALZHEIMER’S INSTITUTE
Caregiver Interventions to Reduce NursingHome Placement of Patients with AD
Intervention
• Counseling sessions – family (4), individual (2)
• Resource and referral information, behavioral management, telephone help
• Weekly support groups
Neurology, 2006
WISCONSIN ALZHEIMER’S INSTITUTE
Caregiver Interventions to Reduce NursingHome Placement of Patients with AD
Results - summary
• Median delay in NHP = 557 days (1.5 years)
• Effects of intervention on NHP due to improvements in caregivers well being (tolerance, depression, satisfaction with support)
• Potential savings of $90,000/patient for 1.5 year delay
Neurology, 2006
WISCONSIN ALZHEIMER’S INSTITUTE
2004 Medicaid Costs for WisconsinNH Residents with Dementia
10,140 persons at $117 per day $455,235,120
State / County Share (40%) $182,094,120
( In 2004, 1600 persons with dementia were served in COP,COP-W and CIP at a cost of $16.7 million)
Potential Long Term Care Savings ofTreating Alzheimer’s Disease in Wisconsin
WISCONSIN ALZHEIMER’S INSTITUTE
• $4.1 million Medicaid savings for delaying NH entry by 1 year for 100 persons
• $5.7 million personal savings for delaying NH entry by 1 year for 100 persons
Source: J Alz Assoc, 2006
Disease Modifying Drugs in Development
WISCONSIN ALZHEIMER’S INSTITUTE
• Tramiprosate (Azhmed) – reduces deposition of Beta amyloid
• Beta secretase inhibitor
– reduced rate of ADL loss by 48%
– reduced rate of cognitive loss by 34%
MMSE – Diagnostic Accuracy
Abnormal (< 24)
%
Normal (≥ 24)
%
Normal 0 100
AD 60 40
Vascular 52 48
Mixed 71 29
Lewy Body 71 29
Frontal Lobe 31 69
Sensitivity – 47
Specificity - 100
WISCONSIN ALZHEIMER’S INSTITUTE
Clock Draw – Diagnostic Accuracy
Abnormal (≤ 8)
%
Normal (> 8)
%
Normal 26 74
AD 87 13
Vascular 82 18
Mixed 86 14
Lewy Body 95 5
Frontal Lobe 71 29
Sensitivity – 77
Specificity - 74
WISCONSIN ALZHEIMER’S INSTITUTE
Animal Fluency – Diagnostic Accuracy
Sensitivity – 90
Specificity - 76
Abnormal (< 17)
%
Normal (> 17)
%
Normal 24 76
AD 91 9
Vascular 90 10
Mixed 100 0
Lewy Body 100 0
Frontal Lobe 100 0
WISCONSIN ALZHEIMER’S INSTITUTE
Wisconsin Dementia Research Consortium Study
WISCONSIN ALZHEIMER’S INSTITUTE
Animal Naming
Diagnostic group Abnormal (< 14) Normal (≥ 14)
Normal Cognition 12% 88%
AD 85% 15%
Other dementia 85% 15%
Animal Naming
WISCONSIN ALZHEIMER’S INSTITUTE
Introduction: “I’d like to ask a question to check your memory.”
Instruction: “Tell me the names of as many animals as you can think of, as quickly as possible.”
Procedure: Time for 60 seconds and record all responses.
If the person stops before 60 seconds, say “Any more animals?”
If the person says nothing for 15 seconds, say “A dog is an animal.Can you tell me more animals?”
1. _______________________ 12. _______________________2. _______________________ 13. _______________________3. _______________________ 14. _______________________4. _______________________ 15. _______________________5. _______________________ 16. _______________________6. _______________________ 17. _______________________7. _______________________ 18. _______________________8. _______________________ 19. _______________________9. _______________________ 20. _______________________10. _______________________ 21. _______________________11. _______________________ 22. _______________________
Scoring: Count the total number of animals (NOT including repetitions or non-animal words): ______________________
dogcatcowpigsheephorseliontigercatmouseant
spraydandelionbird
WISCONSIN ALZHEIMER’S INSTITUTE
LOC ORI ATT LANGUAGE CONST MEM CALC REASONING
COMP REP NAM SIM JUD
†AVG. RANGE -ALERT- --12--
--10--
-(S)7-
--6--
-(S)6-
--5--
--(S)--
--12--
--11--
--(S)--
--8--
--7--
--6--
-(S)5-
--4--
--12--
--10--
-(S)4-
--3
--8--
-(S)6-
--5--
--6--
-(S)5-
--4--
MILD
MODERATE
SEVERE
--IMP--
--8--
--6--
--4--
--5--
--3--
--1--
--4--
--3--
--2--
--9--
--7--
--5--
--5--
--3--
--2--
--3--
--2--
--0--
--8--
--6--
--4--
--2--
--1--
--0--
--4--
--3--
--2--
--3--
--2--
--1--
Write in lower scores
12 7 6 12 8 5 10 4 7 5
COGNITIVE STATUS PROFILE
WAINDZ
Screening Study Data Summary
WISCONSIN ALZHEIMER’S INSTITUTE
LOC ORI ATT LANGUAGE CONST MEM CALC REASONING
COMP REP NAM SIM JUD
†AVG. RANGE -ALERT- --12--
--10--
-(S)7-
--6--
-(S)6-
--5--
--(S)--
--12--
--11--
--(S)--
--8--
--7--
--6--
-(S)5-
--4--
--12--
--10--
-(S)4-
--3
--8--
-(S)6-
--5--
--6--
-(S)5-
--4--
MILD
MODERATE
SEVERE
--IMP--
--8--
--6--
--4--
--5--
--3--
--1--
--4--
--3--
--2--
--9--
--7--
--5--
--5--
--3--
--2--
--3--
--2--
--0--
--8--
--6--
--4--
--2--
--1--
--0--
--4--
--3--
--2--
--3--
--2--
--1--
Write in lower scores
12 7 6 12 8 5 10 4 7 5
COGNITIVE STATUS PROFILE
WAIMCIZ
Screening Study Data Summary
WISCONSIN ALZHEIMER’S INSTITUTE
LOC ORI ATT LANGUAGE CONST MEM CALC REASONING
COMP REP NAM SIM JUD
†AVG. RANGE -ALERT- --12--
--10--
-(S)7-
--6--
-(S)6-
--5--
--(S)--
--12--
--11--
--(S)--
--8--
--7--
--6--
-(S)5-
--4--
--12--
--10--
-(S)4-
--3
--8--
-(S)6-
--5--
--6--
-(S)5-
--4--
MILD
MODERATE
SEVERE
--IMP--
--8--
--6--
--4--
--5--
--3--
--1--
--4--
--3--
--2--
--9--
--7--
--5--
--5--
--3--
--2--
--3--
--2--
--0--
--8--
--6--
--4--
--2--
--1--
--0--
--4--
--3--
--2--
--3--
--2--
--1--
Write in lower scores
12 7 6 12 8 5 10 4 7 5
COGNITIVE STATUS PROFILE
WAISDATZ
Screening Study Data Summary
WISCONSIN ALZHEIMER’S INSTITUTE
Animal Naming screen
Adults > 65 years
Diagnose and Treat Refer to Dementia Diagnostic Clinic
Re-Screen at Intervals
–
Cognistat
+
Referral to MD
_
+
Memory Screening Process
County Services and/or Alzheimer’s Association
County Services and/or Alzheimer’s Association
Cognitive Screening Results – 8 Wisconsin Counties
WISCONSIN ALZHEIMER’S INSTITUTE
Persons approached 1244
Persons screened 1120 (90%)
Persons screened positive 370 (33%) (range 22%-58%)
Abnormal Cognistat 92%
Undertreatment of Alzheimer’s Disease
WISCONSIN ALZHEIMER’S INSTITUTE
• Only 35% of persons with AD have ever been prescribed one of the standard treatments.
Source: J Alz Assoc, 2006