CNADC - Center for Biomedical Imagingbradd/...dementiacourse_neuropsycholo… · • Role of neuropsychology, assessment principles ... American Journal of Alzheimer’s Disease and

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DO NOT COPY OR DISTRIBUTE WITHOUT AUTHORʼS PERMISSION

Sandra Weintraub, Ph.D. Clinical Core Director,

Cognitive Neurology and Alzheimer’s Disease Center Northwestern University Feinberg School of Medicine

©S. Weintraub, CNADC, Northwestern FSM, 2011

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•  Changing concepts of cognitive aging

•  Neurodegenerative disease is focal and affects large-scale neurocognitive networks, producing distinctive neuropsychological profiles of dementia

•  Role of neuropsychology, assessment principles

•  Neuropsychological Profiles Of Dementia: Amnestic, Aphasic, Visuospatial,Comportmental


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25 years 95 years

“Super” Aging

“Normal” Aging

“Mild Cognitive Impairment”

SPECTRUM OF AGE-RELATED COGNITIVE CHANGE: A Race Against Time

“Alzheimer’s Disease or other dementia”

Preclinical

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WMS-III Average For Age

0

10

20

30

40

50

60

16-1718-19

20-2425-29

30-3435-44

45-5455-64

65-6970-74

75-7980-84

85-89

Age Group

Raw

Sco

re E

qu

ivale

nt

of

SS

=1

0

LM1 TSLM IIFACES IFACES IIVPA IVPA IIFAM PICSIFAM PICSIILET NUSpat Span

Evans, Grodstein, Loewenstein, Kaye, Weintraub, JAD, 2011

WHEN DOES CHANGE START?

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DO NOT COPY OR DISTRIBUTE WITHOUT AUTHORʼS PERMISSION ©S. Weintraub, CNADC, Northwestern FSM, 2011

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DIFFERENTIAL DIAGNOSIS

ACUTE/SUBACUTE INSIDIOUS/GRADUAL

Vascular

Metabolic

Toxic Infectious

Paraneoplastic

Epileptic

Neurodegenerative

Tumor

Alzheimerʼs Disease Non Alzheimerʼs Disease

FTLD Diffuse Lewy Body

Hydrocephalus Vascular

Prion Disease TAUOPATHIES

Pick Disease, CBD, PSP Tangle Predominant SD Argyrophiic Grain Disaese FTDP-17 Dementia Pugilistica Etc.

UBIQUITINOPATHIES FUS TDP-43 + NIFID TDP-43- BIBD


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CLINICAL SYNDROME e.g. Progressive

supranuclear palsy Primary progressive aphasia

Adapted from Weintraub and Mesulam, 1993.

NEUROANATOMICAL DISTRIBUTION

e.g., Corticobasal degeneration

GENETIC MUTATIONS e.g., PS1, PS1, PGRN, MAP-T

TISSUE DX e.g., TDP-43 proteinopathy


1:1

??

??

??

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In the absence of biomarkers… Neuropsychological assessment provides:

•  Objective markers of symptoms – is there a

dementia?

•  Early detection

•  Magnitude of change and rate of decline

•  Differential diagnosis

•  Blueprint for management and education


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SEVERE

MODERATE

MILD

Level of Impairment

Late

* McKhann et al, 1984

Amnestic Dementia aka Probable AD

Early


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SEVERE

MODERATE

MILD

Level of Impairment

Late

Early

Progressive Visuospatial Dysfunction Aka Posterior Cortical Atrophy


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1:1

? ? ? ? ?

Initial Neuropsychological Profile

Large-Scale Neuroanatomical Network(Memory, Language,

Visuospatial, Executive)

AD CLBDFTLD-TDP43 FTLD-TAU Vascular

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1:1 Correspondence

90% 10%

Initial Neuropsychological ProfileAMNESIA +

Large-Scale Neuroanatomical NetworkLIMBIC-TEMPORAL

ADOTHER

VascularCLBD

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Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathologica, 2010

Mackenzie IRA, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, et al.

Old terminology 2009 terminology 2010 terminology Associated genes

Tau-positive FTLD FTLD-tau FTLD-tau

Pick disease FTLD-tau (PiD) FTLD-tau (PiD)

MAPT

CBD FTLD-tau (CBD) FTLD-tau (CBD)

Progressive supranuclear palsy FTLD-tau (PSP) FTLD-tau (PSP)

Argyrophilic grain disease FTLD-tau (AGD) FTLD-tau (AGD)

Mult. syst. tauop. w/ dementia FTLD-tau (MSTD) FTLD-tau (MSTD)

Tangle-predom senile dementia FTLD-tau (NFT-dementia) FTLD-tau (NFT-dementia)

WM tauop w/ glob. glial inclusions FTLD-tau (WMT-GGI) FTLD-tau (WMT-GGI)

Unclassifiable tauopathy FTLD-tau (unclassifiable) FTLD-tau (unclassifiable)

Tau-negative FTLD

FTLD-U FTLD-TDP (TDP positive) FTLD-TDP

GRN, VCP, 9p, TARDP Types 1-4 Types 1-4

Unclassifiable Unclassifiable

FTLD-UPS (TDP negative) FTLD-UPS CHMP2B

FTD-3 FTD-3

aFTLD-U

FUS

NIFID FTLD-IF FTLD-FUS

NIFID aFTLD-U

BIBD NIFID

BIBD

DLDH FTLD-ni FTLD-ni ?


INITIAL Behavioral Symptoms and/or Aphasia and/or Motor Symptoms=

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ESTIMATED PEAK PRIOR ABILITY:!•  IQ/Reading SCORES!•  Level and quality of education!•  Career/home accomplishments!•  Civic/social responsibilities!•  Hobbies/recreation!•  Usual emotional reactions!


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Activities of Daily Living Questionnaire (ADL-Q) Johnson, Barion, Rademaker, Rehkemper, Weintraub, ADAD, 2004

Self-Care Household Care Employment/Recreation Shopping/Money

Travel Communication

Mild=0-33%; Moderate=34-66% Severe=>66%

Recreation

0 = Same as usual 1 = Engages in recreational activities less frequently 2 = Has lost some skills necessary for recreational

activities (e.g., bridge, golfing); needs coaxing to participate 3 = No longer pursues recreational activities 9 = Never engaged in recreational activities OR don't know


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Staging TESTS: !"MMSE!"Blessed Dementia Scale (BDS)!"Mattis Dementia Rating Scale!

Montreal Cognitive Assessment! RBANS!

Observer RATINGS:!"Clinical Dementia Rating (CDR)!

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Does the MMSE capture severity in PPA and BvFTD?

–  MMSE most common tool to gauge dementia severity

–  Heavily weighted towards cognitive deficits of AD (memory)

–  Heavily dependent on Language


The MMSE In Behavioral Variant Frontotemporal Dementia And Primary Progressive Aphasia

Osher, Wicklund, Rademaker, Johnson, Weintraub American Journal of Alzheimer’s Disease and Other Dementias, 2007

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Table 1: Sample Demographics

Groups

Demographic Variables bvFTD (N=41) PPA (N=30)

Median 25th-75th%ile Median 25th-75th%ile

Age (years) 61 (56-70) * 67 (62-72)

Education (years) 16 (12-16) 16 (14-16)

Symptom Duration (years) 3 (2-4 ) 4 (2-5 )

MMSE (Total = 30) 23 (18-27) 24 (21-27)

ADLQ (0-100%) 27 (19-40) * * 13 (8-22 )

* bvFTD were significantly younger than PPA (p<.05) ** bvFTD scored significantly higher on the ADLQ than PPA (p<.01) Osher et al AJADD, 2007

\

The MMSE In Behavioral Variant Frontotemporal Dementia And Primary Progressive Aphasia

Osher, Wicklund, Rademaker, Johnson, Weintraub American Journal of Alzheimer’s Disease and Other Dementias, 2007


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Annualized percentage change on the MMSE and the ADLQ

Change Scores

-25%

-20%

-15%

-10%

-5%

0%

% C

hang

e

MMSEADLQ

*

PPA FTD

* p < .05

DEMENTIA SEVERITY: MMSE


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UDS Supplemental CDR: Behavior, Language Ratings Knopman, Weintraub, Pankratz, NEUROLOGY 2011


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Cortical Neuroanatomical Correlates Of Symptom Severity In Primary Progressive Aphasia

Sapolsky, Bakkour, Negreira, Nalipinski, Weintraub, Mesulam, Caplan, Dickerson, Neurology, 2010

PROGRESSIVE APHASIA SEVERITY SCALE (PASS)


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Neurocognitive Domains!

"Attention " " "!"Executive Functions!"Mood/Affect/Behavioral Scales "!"Memory " " "!"Language!"Visuospatial " "!"Reasoning!

"Specialized (neglect; semantic deficits;!"simultanagnosia)!


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•  Select “pure” measures

•  Cover all domains, but be brief

•  Identify PRIMARY DOMAIN Of Deficit

•  Identify “Secondary” symptoms- i.e., word list memory test failed due to aphasia

• Choose tests appropriate for demographics


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•  HARD

•  CVLT, RAVLT

•  Selective Reminding Test

•  Rey-Osterreith Figure; Benton VRT

•  MODERATE

•  WMS Logical Memory

•  WMS Word List or CERAD List (10 items)

•  RBANS Word List; Story; Design

•  EASY

•  Three Words Three Shapes

•  3 words from MMSE ©S. Weintraub, CNADC, Northwestern FSM, 2011

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•  81 yo male •  retired M.D. •  insidious onset •  progressive, 4y •  repetitive, losing belongings •  PMH: CAD allergies,asthma •  CT unremarkable

•  Dementia? Yes •  Memory abn? Yes •  Other abn? EF •  Profile: Amnesia •  DX: PrAD


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Words Learning Trials Recall Trials 60” ND 60” D 3Min

Recognition

apple

shoe

horse

truck

window

1

2

3

4

5

1

2

3

4

5

1

2

3

4

5

1

2

3

4

5

1

2

3

Y/N FP apple + Pencil + Orange + shoe horse Dress + Park truck + Machine window Elbow +

AMNESTIC PROFILE (typical of Alzheimer’s disease)

ND= No distraction D= Distraction

1. Word list = forward digit span minus one

2. Drill to criterion (3 correct successive trials)

3. Test recall after: 60 seconds with no distraction, 60 seconds with distraction, 3 minutes


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1. Word list = forward digit span minus one

2. Drill to criterion (3 correct successive trials)

3. Test recall after: 60 seconds with no distraction, 60 seconds with distraction, 3 minutes

Words Learning Trials Recall Trials 60” ND 60” D 3Min

Recognition

Apple

Shoe

Horse

Truck

Window

1

2 1

2

3

1

2

3

4

1

2

3

4

5

1

2

3

4

5

1

2

3

4

5

1

2

3

4

5

1

2

3

4

Y/N FP Apple + Pencil + None Orange + shoe + Horse + Dress + Park + Truck + Machine + Window + Elbow +

INATTENTIVE PROFILE (toxic/metabolic, depression, FTD, NC)

ND= No distraction D= Distraction

1

2

3

4


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Case 2 •  46 yo, woman, PhD, nurse; insidious onset, progressive, 2 y •  word-finding difficulty •  MRI: Non specific bifrontal atrophy, L>R; Auditory EPs- abn, L temporal •  PMH: breast cancer •  FH: learning disabilities (spelling, writing)

Auditory Comprehension Repetition-Words Repetition-Sentences Oral Reading- Words Oral Reading-Sentences Confrontation Naming Word Fluency Reading Comprehension Praxis-Buccofacial Praxis Limb Calculation Memory-Orientation Memory 3W3S Line Orientation Facial Recognition Hooper VOT Reasoning-Ravenʼs Matrices Reasoning- Shipley Reasoning-Visual-Verbal

0

-20

20

-40

-60

-80 -100

0

-20

20

-40

-60

-80 -100

Language and Related Tests

Non Language Tests

Case 3, Weintraub et al, 1990


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Dementia?

Memory Impaired?

Other Deficits?

Neurocognitive Profile?

DX?

Cause?

Neuroanatomy?


Case 2

YES

NO

NO

Aphasia

L Perisylvian

Primary Progressive Aphasia

FTLD

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M. K.- PPA. Female, onset at age 44. Died 16 years after disease onset.

PATH DX: PICK’S DISEASE

Left Right

STG STG

I I

PO PO

FG MTG MTG ITG ITG

H H


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BOSTON NAMING TEST Kaplan, Goodglass, Weintraub, 1983

Word Frequency


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Cortical Thickness Correlation With NAT Performance in

16 Mixed PPA Patients

X= Inferior frontal gyrus

X


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Domain / Tests (cut off scores

Scores Level

ADL Mattis DRS Total (123/144) ATTENTION DRS ATT (32/37) DRS INIT (29/37) Digit Span (F,B) LANGUAGE Speech BNT (45/60) Verbal fluency Calculations VISUOSPATIAL DRS Construc (4/6) Cube Copy MEMORY DRS Memory (19/25) REASONING DRS Concept (32/39) COMPORTMENT

121

32 23 6,3

60 9

4/8 2

Distorted

25

39

Impaired

Abn

Borderline Abn Abn

Normal NL

Abn Abn

Abn Abn

NL

NL

Normal

•  61 yo man, professional landscaper •  insidious onset •  progressive, 5 y •  Trouble “seeing” •  PMH: none •  CT, MRI, EEG normal

•  Dementia? Yes •  Memory abn? No •  Other abn? Yes •  Profile: Visuospatial

• Pathology: AD vs LBD

•  Anatomy: Parietal; temporo-occipital


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From Weintraub and Mesulam, 2000


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•  61 yo woman, assembly line worker •  Insidious onset •  progressive, 2 y •  “Dwelling” on her birth mother, inattentive, bizarre •  PMH: none •  CT, EEG normal •  Memory abn? No

•  Other abn? Yes •  Profile: Exec/Comport

•  Pathology: FTLD

•  Anatomy: Frontotemporal


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Visual-Verbal Test (Feldman & Drasgow, 1959)

1 2 3 4

SORT 2 1 2 3 4

SHIFT 1 2 3 4

SORT 1


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NC ONC PPA PPA PRAD FTD

NC ONC PPA PPA PRAD FTD

Wicklund, Johnson, Weintraub, 2004

0 0

5 5

10 10

*

*

20 20

10 10

0 0

S H

F T S

I

S O R T S


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NEUROPSYCHOLOGICAL PROFILE: PROGRESSIVE COMPORTMENTAL/EXECUTIVE DYSFUNCTION


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1.  MMSE is normal in an individual with complaints.

2.  Is there cognitive decline beyond age/personal best?

3.  Are there character changes without explanation?

4.  What is the rate of decline? What level of care is needed?

5.  Is treatment having an effect?

Referrals for Neuropsychological Examination


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6. Are cognitive/behavioral changes under age 65 signs of young onset dementia?

7. Can delirium be differentiated from dementia?

8. Is the patient safe/able to live alone? To drive?

9. What can the patient/family do to address cognitive/ behavioral symptoms?

Referrals for Neuropsychological Examination


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Documents

CNADC - Center for Biomedical Imagingbradd/...dementiacourse_neuropsycholo… · • Role of neuropsychology, assessment principles ... American Journal of Alzheimer’s Disease and