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Mild Cognitive Impairment:The Current Status

Mild Cognitive Impairment:Mild Cognitive Impairment:The Current StatusThe Current Status

Ronald C. Petersen, Ph.D., M.D.Mayo Clinic College of Medicine

Rochester, MN

Updates on DementiaStanford University

June 4, 2008

Ronald C. Petersen, Ph.D., M.D.Ronald C. Petersen, Ph.D., M.D.Mayo Clinic College of MedicineMayo Clinic College of Medicine

Rochester, MNRochester, MN

Updates on DementiaUpdates on DementiaStanford UniversityStanford University

June 4, 2008June 4, 2008

DisclosuresDisclosures

• Elan Pharmaceuticals: Chair SMC• GE Healthcare: Consultant

• Elan Pharmaceuticals: Chair SMC• GE Healthcare: Consultant

MILD COGNITIVE IMPAIRMENT

• Conceptual framework• Epidemiology• Clinical features• Outcome• Predictors• Neuropathology• Unresolved issues• Clinical trials



Prevalence of Mild, Moderate/Severe and Total Cases of Alzheimer’s Disease in the United States

2000-2050

Prevalence of Mild, Moderate/Severe and Total Cases of Alzheimer’s Disease in the United States

2000-2050

0

2

4

6

8

10

12

2000

2010

2020

2030

2040

2050

2000

2010

2020

2030

2040

2050

2000

2010

2020

2030

2040

2050

2000

2010

2020

2030

2040

2050

Cas

es (m

illio

ns)

Cas

es (m

illio

ns)

MildMild

CP1266212-1

Mod/severeMod/severe

Delayed disease onset

Delayed disease onset

No therapeutic advances

No therapeutic advances

Delayed disease progression

Delayed disease progression

Both delayed disease onset and delayed disease

progression

Both delayed disease onset and delayed disease

progression

Sloane et al: Ann Rev Pub Health 23:213, 2002Sloane et al: Ann Rev Pub Health 23:213, 2002

Time Course: AD Pathology (in situ) & Time Course: AD Pathology (in situ) & Clinical ExpressionClinical Expression

Path

olog

ical

bur

den

Young Presymptomatic MCI AD

Time

Cog

nitiv

e fu

nctio

n

Pathological progression Cognitive function

40s-60s 60s–70s >70s

2

Cognitive ContinuumCognitive Continuum

Mild CognitiveMild CognitiveImpairmentImpairment

NormalNormal

Alzheimer's DiseaseAlzheimer's Disease

CP926864- 35



Clinical Features

MILD COGNITIVE IMPAIRMENTOriginal Criteria

• Memory complaint • Memory impaired for age• Normal general cognitive function• Normal activities of daily living• Not demented

CaseCase83 y/o Retired Priest

• Word finding difficulties

• Mild memory concerns

• ADL’s preserved

3

83 Y/O PRIEST

• NEUROPSYCHOLOGY PROFILE– VIQ 140– PIQ 110– FSIQ 129– WORKING MEMORY 128– VeMI 92– ViMI 111

83 Y/O PRIEST

• LEARNING EFFIC 104• DELAYED RECALL 71• TRAILS A & B 50% ile• BOSTON NAMING TEST 59/60• FLUENCY 80% ile

34 months laterMILD COGNITIVE IMPAIRMENT

Original Criteria

• Memory complaint • Memory impaired for age• Normal general cognitive function• Normal activities of daily living• Not demented

CP1186552-7

Mild Cognitive ImpairmentClinical Characterization and Outcome

Ronald C. Petersen, PhD, MD; Glenn E. Smith, PhD; Stephen C. Waring, DVM, PhD; Robert J. Ivnik, PhD;

Eric G. Tangalos, MD; Emre Kokmen, MD

Mild Cognitive ImpairmentClinical Characterization and Outcome

Ronald C. Petersen, PhD, MD; Glenn E. Smith, PhD; Stephen C. Waring, DVM, PhD; Robert J. Ivnik, PhD;

Eric G. Tangalos, MD; Emre Kokmen, MD

0

10

20

30MMSEMMSE

02468

10121416

Logical Memory IILogical Memory II

7580859095

100105110

02468

1012141618

Full Scale IQFull Scale IQ

Visual Reproductions IIVisual Reproductions II

ControlsControls MCIMCI ADAD ADADCDRCDR 00 0.50.5 0.50.5 11

ControlsControls MCIMCI ADAD ADADCDRCDR 00 0.50.5 0.50.5 11

CP926864- 3

4

Current Classification Schemefor MCI

Non-amnestic MCISingle domain

NonNon--amnestic MCIamnestic MCISingle domainSingle domain

YesYes

NoNo

Non-amnestic MCINonNon--amnestic MCIamnestic MCI

Single non-memorycognitive domain

impaired?

Single nonSingle non--memorymemorycognitive domaincognitive domain

impaired?impaired?NoNo

Non-amnestic MCIMultiple domain

NonNon--amnestic MCIamnestic MCIMultiple domainMultiple domain



YesYes

NoNo



impaired?





Amnestic MCISingle domainAmnestic MCIAmnestic MCISingle domainSingle domain

YesYes

YesYes

Amnestic MCIAmnestic MCIAmnestic MCI

Memoryimpairment only?

MemoryMemoryimpairment only?impairment only? NoNo

Amnestic MCIMultiple domainAmnestic MCIAmnestic MCI

Multiple domainMultiple domain

Mild Cognitive ImpairmentMild Cognitive Impairment

CP1265413-2Petersen: J Int Med, 2004Petersen: J Int Med, 2004

Cognitive complaintCognitive complaintCognitive complaint

Not normal for ageNot normal for ageNot dementedNot demented

Cognitive declineCognitive declineEssentially normal functional activitiesEssentially normal functional activities

MCIMCIMCI

Memory impaired?Memory impaired?Memory impaired?


YesYes

YesYes





Multiple domainMultiple domainAmnestic MCISingle domainAmnestic MCIAmnestic MCISingle domainSingle domain

YesYes

YesYes





Multiple domainMultiple domainNon-amnestic MCI

Single domainNonNon--amnestic MCIamnestic MCI

Single domainSingle domain

YesYes

NoNo



impaired?






CP1265413-3Petersen: J Int Med, 2004Petersen: J Int Med, 2004




MCIMCIMCI


Petersen: J Int Med, 2004Petersen: J Int Med, 2004


CP1265413-4



YesYes

NoNo



impaired?






YesYes




YesYes


MCIMCIMCI





Multiple domainMultiple domain

MCI OutcomesMCI Outcomes

CP1265413-5

ADAD

ADAD

FTDFTD

DLBDLB

DeprDepr

DeprDepr

VCIVCI

VCIVCI

SingledomainSingle

domain

Multipledomain

Multipledomain

SingledomainSingle

domain

Multipledomain

Multipledomain

Clin

ical

cla

ssifi

catio

nC

linic

al c

lass

ifica

tion

AmnesticMCI

AmnesticMCI

Non-amnestic

MCI

Non-amnestic

MCI

EtiologyEtiologyDegen-erativeDegenDegen--erativeerative VascularVascularVascular PsychiatricPsychiatricPsychiatric Med CondMed Med CondCond

MCI OutcomesMCI Outcomes

CP1265413-6

ADAD

ADAD

FTDFTD

DLBDLB

DeprDepr

DeprDepr

VCIVCI

VCIVCI

SingledomainSingle

domain

Multipledomain

Multipledomain

SingledomainSingle

domain

Multipledomain

Multipledomain

Clin

ical

cla

ssifi

catio

nC

linic

al c

lass

ifica

tion

AmnesticMCI

AmnesticMCI

Non-amnestic

MCI

Non-amnestic

MCI

EtiologyEtiologyDegen-erativeDegenDegen--erativeerative VascularVascularVascular PsychiatricPsychiatricPsychiatric Med CondMed Med CondCond

5



Mild Cognitive Impairment

MCI MCI → → AD 12%/yrAD 12%/yr Control Control → → AD 1AD 1--2%/yr2%/yr

Petersen RC et al: Arch Neurol 56:303Petersen RC et al: Arch Neurol 56:303--308, 1999308, 1999

50

60

70

80

90

100

50

60

70

80

90

100

Initial 12 24 36 48exam

CP926864- 12

MonthsInitial 12 24 36 48exam Months

0.71

0.13

0.380.47

0.11

-0.25

-0.45

-0.10 -0.12 -0.05

-1.0

-0.5

0.0

0.5

1.0

Memory Language Attention Visuospatial Composite

MOANS Change ScoresMOANS Change Scores

CP1273076-3

NormalNormalMCIMCI

MCI StudiesMCI StudiesMCI Studies

16.3%16.3%

----

24.0%24.0%

15.0%15.0%

16.1%16.1%

19.3%19.3%

MCI MCI PrevalencePrevalence

(10%)(10%)7070--898919691969MayoMayo

18.3%18.3%65+65+206206Cache Cache CountyCounty

19.5%/10.7%19.5%/10.7%7575--7676581581ViennaVienna

----6767960960IndiaIndia

13.6%13.6%6565--848428302830ItalyItaly

8.7%8.7%75+75+980980LeipzigLeipzig

Progression Progression RateRate

AgeAgeNumber of Number of SubjectsSubjects

StudyStudy



MILD COGNITIVE IMPAIRMENTPredictors of Outcome

• Apo-E Status+E4

• Clinical severity• Hippocampal volumes• ? FDG-PET• ? CSF Biomarkers• ? Amyloid imaging

6

MCI: Conversion to Dementia

%%

YearsYears

0

20

40

60

80

100

0 1 2 3 4 5 6

APOE 4 APOE 4 noncarriernoncarrier

APOE 4 carrierAPOE 4 carrier

CP926864- 13

Hippocampus & ERC volume Measurement - tracing

Atrophy and AD StageAtrophy and AD Stage

Control, 70 F MCI, 72 F AD, 74 F

83 yo male1993 MCI 1996 1997MMSE=27 MMSE=27 MMSE=27

1999 2001 converted to AD 2003MMSE=28 MMSE=25 MMSE=22

0

25

50

75

100

0 1 2 3 4 5 6

StableStable(%)(%)

YearsYears

No atrophyNo atrophy

Mild atrophyMild atrophy

ModMod--severe atrophysevere atrophy

CP926864- 15

Boundary Shift IntegralBoundary Shift Integral

7

Scan 1

Scan 2

Boundary Boundary Shift Shift

IntegralIntegral New Neuroimaging Research

Voxel-based Morphometry

VBM VBM Normal(43) Normal(43)

vs vs AD (51)AD (51)

ADaMCI

n=88 n=51

VBMWhitwell

MCI Converter vs NonMCI Converter vs Non--ConverterConverter

0

8T score

L R 0

8T score

L R

VoxelVoxel--wise methods capture time dependent wise methods capture time dependent progression from aMCI to AD progression from aMCI to AD n = 33n = 33

MCI3 years before conversion to AD

MCI1 year before conversion to AD

ADAt time of conversion to AD

L R RL RL

3D Maps from Multiple MRI Illustrate Changing Atrophy Patterns as Subjects Progress from MCI to AD Whitwell, Jack, Brain 2007

8

NCI MCI mADNCI MCI mAD

Synapse Number and Volume Loss in CA1 in MCISynapse Number and Volume Loss in CA1 in MCI

Scheff et al: Neurol 68:1501, 2007Scheff et al: Neurol 68:1501, 2007

Syna

pses

x 1

010Sy

naps

es x

10

Syna

pses

x 1

01010

CP1307284-5

Total No. of SynapsesTotal No. of SynapsesTotal No. of Synapses40

30

20

10

0

Volu

me

(mm

3 )Vo

lum

e (m

mVo

lum

e (m

m33 ))

Total VolumeTotal VolumeTotal Volume300

200

100

0

Molecular Neuroimaging

In vivo Amyloid Imaging withPittsburgh Compound B (PIB)

N

SNH11CH3

HO

PET Imaging -[11C]6-OH-BTA-1 (PIB)

N

SN

CH3

CH3

H3C

CH

+

6 1

Histology - Thioflavin T

Amyloid Plaques

FDG and PIB in Aging and AD

AD -FDG

AD-PIB

Normal Control -PIB

PIB in Controls, MCI, ADChet Mathis, U Pittsburgh

Some MCI’s have control-like PIB retention, some have AD-like retention, and some have intermediate retention

Price et al., JCBFM 2005Lopresti et al., J Nucl Med, in press

02-310-847 06-209-892

3

2.5

2

1.5

1

0.5

0

PIB IdealizedPIB Idealized

aMCI AD

00-863-895

CN

9

02-155-940 02-310-847 06-209-892

3

2.5

2

1.5

1

0.5

0

PIB Examples PIB Examples –– full spectrumfull spectrumL

owH

igh

CN aMCI AD

00-863-895 01-873-114

CN aMCI

Cerebrospinal FluidCerebrospinal Fluid

Hansson et al: Lancet Neurol 5:228, 2006Hansson et al: Lancet Neurol 5:228, 2006

0.0

0.2

0.4

0.6

0.8

1.0

0 10 20 30 40 50 60

No

prog

ress

ion

to A

DN

o pr

ogre

ssio

n to

AD

CP1266212-4

MonthsMonths

Normal CSFNormal CSF

Pathological CSFPathological CSF

Progression to AD from MCIProgression to AD from MCI Progression Normal to MCICSF Ratio

Progression Normal to MCICSF Ratio

Li et al: Neurol 69:631, 2007Li et al: Neurol 69:631, 2007

0.0

0.2

0.4

0.6

0.8

1.0

0 10 20 30 40 50

Prop

ortio

n re

mai

ning

as c

ontr

olPr

opor

tion

rem

aini

ngPr

opor

tion

rem

aini

ngas

con

trol

as c

ontr

ol

CP1307284-4

MonthsMonthsMonths

Normal >53 yr (n=26)Normal >53 yr (n=26)Normal >53 yr (n=26)

High (n=17)High (n=17)High (n=17)

0 1 2 3 4 5 6 7 8 9

1.0

0.8

0.6

0.4

0.2

0

Predicting Progression to CDR >0Predicting Progression to CDR >0

Fagan et al: Arch Neurol 64:343, 2007Fagan et al: Arch Neurol 64:343, 2007

Prop

ortio

n re

mai

ning

CD

R 0

Prop

ortio

n re

mai

ning

CD

R 0

Prop

ortio

n re

mai

ning

CD

R 0

CP1307284-7

Time since baseline clinical assessment (yr)Time since baseline clinical assessment (yr)Time since baseline clinical assessment (yr)

CSF tau/Aβ42CSF tau/ACSF tau/Aββ4242

0 1 2 3 4 5 6 7 8 9

CSF ptau181/Aβ42CSF ptauCSF ptau181181/A/Aββ4242

<1.15<1.15<1.15

≥1.15≥≥1.151.15

<0.214<0.214<0.214

≥0.214≥≥0.2140.214

Alzheimer’s Disease Neuroimaging Initiative

ADNI

Alzheimer’s Disease Neuroimaging Initiative

ADNI

10

ADNIADNI

•• Observational study of imaging and Observational study of imaging and biomarkersbiomarkers

•• NormalsNormals = 200= 200•• MCI = 400MCI = 400•• AD = 200AD = 200

•• MRI, FDG PET, MRI, FDG PET, PiBPiB, CSF, biomarkers, CSF, biomarkers•• 3 years3 years

ADNI DemographicsADNI Demographics

CP1307278-1

Normal controls MCI AD(n=229) (n=398) (n=192) P

Age, mean (SD) 76.4 (5.0) 75.3 (7.5) 75.8 (7.4) 0.15

Female (%) 48.0 35.4 47.4 0.002

Years of education, 15.6 (3.1) 16.0 (2.9) 14.7 (3.1) <0.001mean (SD)

Apolipoprotein E e4: 26.6 53.5 65.6 <0.001Positive (%)

Normal controls MCI AD(n=229) (n=398) (n=192) P

Age, mean (SD) 76.4 (5.0) 75.3 (7.5) 75.8 (7.4) 0.15

Female (%) 48.0 35.4 47.4 0.002

Years of education, 15.6 (3.1) 16.0 (2.9) 14.7 (3.1) <0.001mean (SD)

Apolipoprotein E e4: 26.6 53.5 65.6 <0.001Positive (%)

ADNI Cognitive FunctionADNI Cognitive Function

CP1307278-2

Normal MCI AD(n=229) (n=398) (n=192)

Estimated premorbid 119.8 (9.0) 116.2 (9.7) 113.6 (9.9)verbal IQMemory

Auditory verbal learningTrials 1-5 correct 43.3 (9.09) 30.7 (9.03) 23.2 (7.70)Delayed recall (%) 65.8 (27.6) 32.1 (31.4) 11.3 (21.9)

LanguageBoston Naming 27.9 (2.3) 25.5 (4.1) 22.3 (6.2)Category fluency total 34.6 (8.1) 26.7 (7.5) 20.3 (7.5)

Executive functionTrail A time 36.5 (13.2) 44.8 (22.8) 68.2 (36.8)Trail B time 89.2 (44.3) 130.5 (73.5) 199.6 (86.8)Digit symbol correct 45.7 (10.2) 36.9 (11.1) 26.7 (12.9)

Visuospatial abilityClock draw: Copy 4.86 (0.43) 4.65 (0.68) 4.31 (1.00)

AttentionDigit span: Forward 8.78 (1.99) 8.22 (2.01) 7.54 (1.94)Digit span: Backward 7.21 (2.16) 6.17 (2.2) 4.96 (1.83)

Normal MCI AD(n=229) (n=398) (n=192)







ADNI Cognitive FunctionADNI Cognitive Function

CP1307278-2

Normal MCI AD(n=229) (n=398) (n=192)







Normal MCI AD(n=229) (n=398) (n=192)







ADAS-Cog BaselineADAS-Cog Baseline

CP1307278-4

0

10

20

30

40

NC MCI AD

Tota

l11

Tota

l11

0

10

20

30

40

50

0 4 8 120

10

20

30

40

50

0 4 8 12

ADAS-CogADAS-Cog

CP1307278-5

TimeTime

MCIMCI

0

10

20

30

40

50

0 4 8 12

Tota

l11

Tota

l11

TimeTime

NCNC

Tota

l11

Tota

l11

Tota

l11

Tota

l11

TimeTime

ADAD

11

ADAS-Cog Annual ChangeADAS-Cog Annual Change

CP1307278-7

NC MCI AD

-10

0

10

20

30

NC MCI AD

AVLT Learning Over TrialsAVLT Learning Over Trials

CP1307278-9

Neu

roba

tN

euro

bat

10

20

30

40

70

50

60

AVLT Learning Over TrialsAVLT Learning Over Trials

CP1307278-10

TimeTime

MCIMCI

Neu

roba

tN

euro

bat

TimeTime

NCNC

Neu

roba

tN

euro

bat

Neu

roba

tN

euro

bat

TimeTime

ADAD

0

10

20

30

40

50

60

70

0 4 8 120

10

20

30

40

50

60

70

0 4 8 120

10

20

30

40

50

60

70

0 4 8 12 NC MCI AD

AVLT Annual ChangeAVLT Annual Change

CP1307278-12

-30

-20

-10

20

0

10

Diagnostic ConversionsDiagnostic Conversions

CP1307278-18

NL198NL198

MCI302MCI302

AD142AD142

Normal → MCI 2%Normal → MCI 2%

MCI → AD 18%MCI → AD 18%

194194 241241 140140

2277

44 5454

Amnestic MCIBaseline DataAmnestic MCIBaseline Data

CP1309880-2

ADCS ADNI UDS MCSA

No.

Age

Educ

MMSE

CDR, SoB

ADAS-Cog

ADCS ADNI UDS MCSA

No.

Age

Educ

MMSE

CDR, SoB

ADAS-Cog

259 398 2,128 241259 398 2,128 241

72.9 (7.6) 75.3 (7.5) 76.1 (9.6) 82.0 (5.2)72.9 (7.6) 75.3 (7.5) 76.1 (9.6) 82.0 (5.2)

14.7 (3.1) 16.0 (2.9) 14.5 (3.5) 13.1 (3.5)14.7 (3.1) 16.0 (2.9) 14.5 (3.5) 13.1 (3.5)

27.3 (1.8) 27.0 (1.8) 26.9 (2.7) 25.4 (2.5)27.3 (1.8) 27.0 (1.8) 26.9 (2.7) 25.4 (2.5)

1.9 (0.8) 1.6 (0.9) 1.4 (1.2) 0.9 (1.0)1.9 (0.8) 1.6 (0.9) 1.4 (1.2) 0.9 (1.0)

11.0 (4.2) 11.5 (4.4) – –11.0 (4.2) 11.5 (4.4) – –

12

Amnestic MCIFirst 12-Month Change

Amnestic MCIFirst 12-Month Change

CP1309880-1

ADCS ADNI UDS MCSA

MMSE

CDR, SoB

ADA-Cog

ADCS ADNI UDS MCSA

MMSE

CDR, SoB

ADA-Cog

-0.8 (2.3) -1.0 (2.0) -0.6 (2.8) -0.1 (3.1)-0.8 (2.3) -1.0 (2.0) -0.6 (2.8) -0.1 (3.1)

+0.4 (1.3) +0.7 (1.3) +0.5 (1.4) +0.4 (1.1)+0.4 (1.3) +0.7 (1.3) +0.5 (1.4) +0.4 (1.1)

+0.6 (4.1) +1.0 (4.5) – –+0.6 (4.1) +1.0 (4.5) – –

Breadth of MCI Research

• Epidemiology• Clinical• Imaging• Biomarkers• Mechanism of disease• Neuropathology• Clinical trials

CP1186552-8

Practice Parameter: Early Detection of Dementia: Mild Cognitive Impairment

(an Evidence-Based Review)Report of the Quality Standards Subcommittee

of the AmericanAcademy of NeurologyRonald C. Petersen, PhD, MD; J. C. Stevens, MD;

M. Ganguli, MD, MPH; E. G. Tangalos, MD;J. L. Cummings, MD; and S. T. DeKosky, MD





AAN PRACTICE PARAMETERDETECTION SUMMARYRECOMMENDATIONS

• GUIDELINE– PATIENTS WITH A MILD COGNITIVE

IMPAIRMENT SHOULD BE RECOGNIZED AND MONITORED FOR A COGNITIVE AND FUNCTIONAL DECLINE DUE TO THEIR INCREASED RISK FOR SUBSEQUENT DEMENTIA

Publications on MCIPublications on MCI

050

100150200250300350400450500550600650700750800850900

1990 91 92 93 94 95 96 97 98 99 2000 01 02 03 04 05 06 07

YearYear

Art

icle

s (n

o.)

Art

icle

s (n

o.)

CP1265393-4CP1186552-8









13

CP1266212-9

Petersen and O’Brien: J Geriat Psych and Neurol 19:147, 2006Petersen and O’Brien: J Geriat Psych and Neurol 19:147, 2006

So, is MCI too late?So, is MCI too late?

CP1307284-1

Jagust: Neurol 70:502, 2008Jagust: Neurol 70:502, 2008

NIA-REAGANNIANIA--REAGANREAGAN

CP1183543-12

%%

NormalsNormalsMCIMCIADAD

0

20

40

60

80

100

Low Intermed High

Pathological Outcome of MCIPathological Outcome of MCI

AD 71%

DLB 9%

Hippocampal sclerosis 6%

FTD 3%

PSP 3%

AGD 3%

Non-specific tauopathy 6%

Vascular 3%

ADPresympPresymp MCIMCI DementiaDementiaNormalNormal

ClinicalClinical

CP1217145-1

14

Braak2

Braak2

Braak3

Braak3

Braak4

Braak4

Braak5

Braak5

Braak6

Braak6

APPAPP FibrilsFibrilsOligo’sOligo’s ProtofibrilsProtofibrils PlaquesPlaques

Braak1

Braak1

CP1217145-2

Neurofibrillary tanglesNeurofibrillary tangles

AmyloidAmyloid

NeuropathologicalNeuropathologicalClinicalClinical

CP1217145-3

PresympPresymp DementiaDementiaNormalNormal MCIMCI

PathologicalPathological

APPAPP

Braak4

Braak4

Braak5

Braak5

Braak6

Braak6

Braak1

Braak1

FibrilsFibrils PlaquesPlaques

Braak2

Braak2

Braak3

Braak3

Oligo’sOligo’s ProtofibrilsProtofibrils

AmyloidAmyloid

Neurofibrillary tangles

Neurofibrillary tangles

AD?AD?

Presymptomatic MCI ADNormal

aMCI criteria, degenerativeAPOE statusMRI structuralFDG-PETCSF tau, AβAmyloid imaging

NormalcognitionAPOE statusMRI structuralFDG-PETCSF tau, AβAmyloid imaging

aMCI criteria, degenerativeAPOE statusMRI structuralFDG-PETCSF tau, AβAmyloid imaging

MCI SUMMARY

• USEFUL CONCEPT• CRITERIA AVAILABLE

– CLINICIAN INVOLVED– ALOGORITHM

• OUTCOME DEPENDENT• NEUROPATH TRANSITIONAL• CLINICAL TRIALS FEASIBLE

MAYO ALZHEIMER’S DISEASE RESEARCH CENTER

• Rochester– Brad Boeve– David Knopman– Eric Tangalos– Joe Parisi– Cliff Jack– Walter Rocca– Bob Ivnik– Glenn Smith– Rosebud Roberts– Shane Pankratz– Yonas Geda

• Jacksonville– Steve Younkin– Dennis Dickson– Neill Graff-Radford– Shu-Hui Yen– Todd Golde– Mike Hutton– John Lucas– Tanis Ferman– Floyd Willis

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