Dementia: Delivering the Diagnosis Daniel D. Christensen, M.D. Clinical Professor of Psychiatry Clinical Professor of Neurology Adjunct Professor of Pharmacology

Dementia: Deliveringthe Diagnosis


Daniel D. Christensen, M.D.Clinical Professor of PsychiatryClinical Professor of Neurology

Adjunct Professor of PharmacologyUniversity of Utah



Diagnosing Dementia – Diagnosing Dementia – What to Tell the Patient and FamilyWhat to Tell the Patient and Family

Geriatrics and Aging 2005; 8,48-51Geriatrics and Aging 2005; 8,48-51

““No more than 50% of physiciansNo more than 50% of physiciansregularly disclose the diagnosisregularly disclose the diagnosis

to patients with dementiato patients with dementia

WHY?WHY?

““They’re already upset enough”.They’re already upset enough”.

““It will only make it worse”.It will only make it worse”.

Myth #1Myth #1

Anxiety level in patients and caregiversAnxiety level in patients and caregiversBefore and after the disclosure of a dementia diagnosisBefore and after the disclosure of a dementia diagnosis

J Am Geriart Soc 2008;56:405-412J Am Geriart Soc 2008;56:405-412

Depression in patients and caregiversDepression in patients and caregiversBefore and after the disclosure of a dementia diagnosisBefore and after the disclosure of a dementia diagnosis

J Am Geriart Soc 2008;56:405-412J Am Geriart Soc 2008;56:405-412

“… the vast majority of older individuals wouldwant to know their diagnosis if they developed AD”.

Grossberg, 2008; Ouimet, 2004; Turnbull, 2003; Eison, 2006Grossberg, 2008; Ouimet, 2004; Turnbull, 2003; Eison, 2006

“I have my diagnosis, and I know I have Alzheimer’s … it’sjust a matter of making the best of it …You know, I mean

every day is a new day and it always brings new challenges.I think that’s the way life is anyway”.

““You can never be sure of the diagnosis.You can never be sure of the diagnosis.

Why just give them a guess”.Why just give them a guess”.

Myth #2Myth #2

It is true that there are currently no clinically availableIt is true that there are currently no clinically available

laboratory, neurologic or neuroimaging findings whichlaboratory, neurologic or neuroimaging findings which

provide absolute confirmation of the diagnosis.provide absolute confirmation of the diagnosis.

A. 10%

B. 50%

C. 85%

D. 98%

A. 10%

B. 50%

C. 85%

D. 98%

Rex meets DSM IV and NINCDS-ADRDAdiagnostic criteria for probable Alzheimer’sDisease. What is the probability that he willmeet pathologic diagnostic criteria for AD atautopsy?

Rex meets DSM IV and NINCDS-ADRDAdiagnostic criteria for probable Alzheimer’sDisease. What is the probability that he willmeet pathologic diagnostic criteria for AD atautopsy?

J Am Geriatric Society 1999; 47: 564 - 569Alz Disease and Assoc Disorders 1996; 10: 180 - 188

Neurology 1995; 45: 461 - 466Neurology 2000; 55: 1854 - 1862

J Am Geriatric Society 1999; 47: 564 - 569Alz Disease and Assoc Disorders 1996; 10: 180 - 188

Neurology 1995; 45: 461 - 466Neurology 2000; 55: 1854 - 1862

Predictive value of clinicaldiagnostic criteria for Alzheimer’s

Predictive value of clinicaldiagnostic criteria for Alzheimer’s

About 85% of those who meet diagnosticcriteria during life will meet neuropathologiccriteria for Alzheimer’s Disease at autopsy.

(Range 75 - 97%)

About 85% of those who meet diagnosticcriteria during life will meet neuropathologiccriteria for Alzheimer’s Disease at autopsy.

(Range 75 - 97%)

““It doesn’t make any difference. YouIt doesn’t make any difference. Youcan’t do anything about it anyway”.can’t do anything about it anyway”.

Myth #3Myth #3

If patients and families know the diagnosis they can:-Better plan and prepare for the future

Estate planningPower of attorneyAdvance directives

- Mentally & emotionally prepare for what is to come

-Make decisions about their health care

- Express preferences regarding choices they will beunable to make in the future

AChEI Class Efficacy: Cognition AChEI Class Efficacy: Cognition

•At the end of one year, all three agents show At the end of one year, all three agents show no statistically significant decline from no statistically significant decline from

baseline on cognitive testsbaseline on cognitive tests

Donepezil Donepezil (MMSE)(MMSE)

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

0 12 24 36 52

‡†

*

* p=0.0005† p=<0.05‡ p=0.001

donepezil HCIplacebo

Study Week 6 Months 1 Year

ClinicalImprovement

ClinicalDeclineL

S M

ean

Ch

ang

eF

rom

Bas

elin

e (±

SE

)

Donepezil Donepezil (MMSE)(MMSE)

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

0 12 24 36 52

‡†

*

* p=0.0005† p=<0.05‡ p=0.001

donepezil HCIplacebo

Study Week 6 Months 1 Year

ClinicalImprovement

ClinicalDeclineL

S M

ean

Ch

ang

eF

rom

Bas

elin

e (±

SE

)

GalantamineGalantamine (ADAS(ADAS--cog)cog)

Me

an (

+S

E)

cha

nge

in A

DA

S-

cog

from

bas

elin

e

-4

-3-2

-10

12

3

456

7

3 6 9

Time (months)

Deterioration

Improvement

Open-ExtensionOpen-ExtensionDouble Blind

12Galantamine 16-24mg

Placebo

Placebo/Galantamine

RivastigmineRivastigmine (ADAS(ADAS--cog)cog)

RivastigmineRivastigmine 66--12 mg/day12 mg/day

PlaceboPlacebo

Dose Dose optimization optimization with with rivastigminerivastigmine

Projected placeboProjected placebo

ImprovementImprovement

AD

AS

AD

AS-- C

og T

est Sco

reC

og T

est Sco

reWorseningWorsening

22

11

00

--11

--22

--33

--44

--55

--66

--77

--8800 1212 1818 2626 3838 4444 5252

Weeks

Long Term effects: ADL and CognitionAD2000 Study (donepezil)Long Term effects: ADL and CognitionAD2000 Study (donepezil)

Remaining subjectsRemaining subjectsDonepezilDonepezil 282282 262 220 262 220 182 162 182 162 157 157 8181

PlaceboPlacebo 283 269 283 269 230 185 230 185 162 160 162 160 74 74

AD2000 Collaborative Group.AD2000 Collaborative Group. Lancet. Lancet. 2004;363 (9427):2105-2115 2004;363 (9427):2105-2115

DonepezilDonepezil

PlaceboPlacebo

Ch

an

ge

Ch

an

ge

Fro

m B

aselin

eFro

m B

aselin

e BetterBetter

Time (weeks)Time (weeks)

Treatment effect 0.83Treatment effect 0.83(SE 0.18) (SE 0.18)

PP<0.0001<0.0001

WorseWorse-8-8

-6-6

-4-4

-2-2

00

22 00 1212 2424 3636 4848 6060 7272 8484 9696 108108120120

MMSE

Functional Response:No mean ADL change 1 year (galantamine)

Functional Response:No mean ADL change 1 year (galantamine)

Galantamine 24 mg/Galantamine 24 mg

Improvement

Deterioration

Mean (± SE)Change From

Baseline InDAD

Pooled placebo data; Galantamineand historical placebo groups

*Not significantly different from baseline.

Time (months)0 3 6 9 12

–14

–12

–10

–8

–6

–4

–2

0

2

*

Open-Extension

Double-blind

Raskind, et al, Neurology, 2000.

Behavioral Response: Delayed adverse behaviors (galantamine)Behavioral Response: Delayed adverse behaviors (galantamine)

*P < .05 vs placebo (both doses).†P < .05 vs baseline.

Mean (± SE)Change From

Baseline InNPI

Reference: Tariot, et al, Neurology, 2000.

Galantamine 24 mg/d

Placebo

Galantamine 16 mg/d

Improvement

Deterioration

3

2

1

0

–1

–2

–3

–4

–5

–6

*

0 3 51

Months

Dose Increments

†

Memantine in Moderate-to-Severe ADCognitive and Functional EffectsMemantine in Moderate-to-Severe ADCognitive and Functional Effects

Reisberg et al, NEJM 2003;348:1333-41

2

0

- 2

- 4

- 6

- 8

-10

-12

0 4 12 28 End Point

Weeks

Dif

fere

nce

in

SIB

Severe Impairment BatterySevere Impairment Battery

1

0

-1

-2

-3

-4

-5

-6

-7

0 4 12 28 End PointWeeks

Dif

fere

nce

in

AD

CS

-AD

L s

ev s

core

Activities of Daily LivingActivities of Daily Living

Memantine Placebo

Memantine in Moderate-to-Severe ADCombined Effect with Donepezil (cognitive)Memantine in Moderate-to-Severe ADCombined Effect with Donepezil (cognitive)

Tariot et al, JAMA 2004;291:317-324

0 4 8 12 18 24

0

4

3

2

1

-1

-2

-3

-4

Memantine+donepezil Placebo+donepezil

Dif

fere

nce

in

SIB

Weeks

End Point (LOCF)

Theoretical Outcome withTheoretical Outcome withDisease-Modifying TreatmentDisease-Modifying Treatment

Cog

niti

on

Time

Treatment begun

“The early diagnosis has given me time to enjoy the lifeI have now. I also have the faculties to appreciate the

simple things: a beautiful sunset, a tree in the spring …Yes, having Alzheimer’s has changed my life; it has made

me appreciate life more. I no longer take things for granted”.

““I’m not sure what to say”.I’m not sure what to say”.

Barrier to DisclosureBarrier to Disclosure

General guidelines

Spouse or family members present (with patient’s consent)Spouse or family members present (with patient’s consent)Private, quiet, comfortable setting with adequate timePrivate, quiet, comfortable setting with adequate timeReview the testing that has been done and what it meansReview the testing that has been done and what it meansUse the word “Alzheimer’s”Use the word “Alzheimer’s”Emphasize current capabilities and maintaining functionEmphasize current capabilities and maintaining functionBe a partner and advocate for patient and caregiverBe a partner and advocate for patient and caregiverProvide educational resources and necessary referralsProvide educational resources and necessary referralsDiscuss pharmacotherapy and lifestyle changesDiscuss pharmacotherapy and lifestyle changesMention ongoing research into causes and treatmentsMention ongoing research into causes and treatmentsOffer clinical trials, if availableOffer clinical trials, if availableAnswer any questionsAnswer any questionsSchedule another time for followup and further discussionSchedule another time for followup and further discussion

Discussion with Rex and Karen

SummarySummaryAn open direct discussion following an Alzheimer’s An open direct discussion following an Alzheimer’s

diagnosis:diagnosis:

- Will usually decrease anxiety and concern- Will usually decrease anxiety and concernboth in the patient and familyboth in the patient and family

-Will allow patients and families to make necessary plansWill allow patients and families to make necessary plansand decisionsand decisions

-Should be supportive, reassuring and emphasizeShould be supportive, reassuring and emphasizecurrent abilities and preservation of function current abilities and preservation of function







Documents

Dementia: Delivering the Diagnosis Daniel D. Christensen, M.D. Clinical Professor of Psychiatry Clinical Professor of Neurology Adjunct Professor of Pharmacology