A Brief History Classification of FTDfaculty.wcas.northwestern.edu/~paller/mdrs/johnH.pdf · A...
Transcript of A Brief History Classification of FTDfaculty.wcas.northwestern.edu/~paller/mdrs/johnH.pdf · A...
Semantic Dementia asa Disorder of Memory
John R. Hodges
MRC-CBU Cambridge and University ofCambridge
MRC CBU
A Brief History
z 1890s Arnold Pick: amnestic aphasia inpatients with left temporal atrophy
A Brief History
z 1975 Warrington: “Selective loss ofsemantic memory”
z 1982 Mesulam “Primary progressiveaphasia”
z 1989 Snowden et al “Semantic dementia”
z 1992 Hodges et al. “Semantic dementia:progressive fluent aphasia with lefttemporal lobe atrophy”
Classification of FTD(Neary et al. 1998 Neurology 51, 1546-54)
Disinhibited variant Apathetic variant
FTD Semantic dementia Prog nonfluent aphasia
FTLD
Semantic dementia(Neary et al. 1998)
z Insidious onset and gradual progressionz Language disorder characterised by
y Fluent empty spontaneous speechy Loss of word meaning: impaired comprehension and namingy Semantic paraphasias
z Perceptual disorder characterised byy Prosopagnosia and/ory Associative agnosia
z Preserved matching and drawingz Preserved single word reading
Semantic dementia: Our view
z Progressive loss of verbal and non-verbal semanticmemory
Semantic dementia
z Progressive loss of verbal and non-verbal semanticmemory
z Preservation of other cognitive domains (e.g.., workingmemory, visuo-spatial ability, non-verbal problemsolving ability, phonology & syntax)
Semantic dementia
z Progressive loss of verbal and non-verbal semanticmemory
z Preservation of other cognitive domains (e.g., workingmemory, visuo-spatial ability, non-verbal problemsolving ability, phonology & syntax)
z Good orientation and recall of recent events
Semantic dementia
z Progressive loss of verbal and non-verbal semanticmemory
z Preservation of other cognitive domains (e.g., workingmemory, visuo-spatial ability, non-verbal problemsolving ability, phonology & syntax)
z Good orientation and recall of recent events
z Atrophy to the infero-lateral temporal neocortex withrelative preservation of the hippocampus early in thedisease
Three cases of semanticdementia
z Case A: mild
z Case B: moderate
z Case C: severe
Patient A
z 50 year-old woman, university education
z 24 months word finding difficulty and “lossof memory for words”
z No impairment in conversationalcomprehension
z Intact everyday activities
Patient A
z Verbal fluency reduced for living andmanmade items: 50% of normal
z Easy naming test: 92%
z Hard (Graded) naming test: 30%Semantic errors
Semantic BatteryGraded Naming Test
Easy Hard
Patient A
z Verbal fluency reduced for living and manmadeitems: 50% of normal
z Easy naming test: 92%z Hard (Graded) naming test: 30% Semantic
errorsz Word-picture matching and pyramids and
palmtrees: 100%z Visuo-spatial skills, problem solving, non-verbal
memory: all normal
Patient A
z MRI: anteriorleft TL atrophy
Diagnosis: Primary progressive aphasia: purelyanomic?
Patient A: Is comprehensionnormal?
z Synonym judgement impairedy Rogue scoundrel polka gasket
y Humour whiff wit carbon
y Impetus equity motivationmisconception
WP-Matching Level 0 WP-Matching Level 1
WP-Matching Level 2 WP-Matching Level 3
Mean effect of semantic distanceon Word-to-Picture Matching
0.3
0.35
0.4
0.45
0.5
0.55
0.6
L0 L1 L2 L3
Patient A: Is comprehensionnormal?
z Synonym judgement impaired
z Definitions of word meaning also impaired
z Word comprehension deficits are present iftested using harder tests
z Still PPA: fluent type?
Patient B
z 48 months word finding difficulty and “lossof memory for words”
z Spouse noted impairment incomprehension
z Intact everyday activities
z Becoming rigid and rather obsessional
Patient B
z Verbal fluency reduced for living andmanmade items: 20% of normal
z Easy naming test: 41%
z Hard (Graded) naming test: 0%
Patient B
z Verbal fluency reduced for living and manmadeitems: 20% of normal
z Easy naming test: 41%z Hard (Graded) naming test: 0%z Word-picture matching: 80%z Visuo-spatial skills, problem solving, non-verbal
memory: all normalz Normal use of objects in everyday life
Patient B
z Left anteriorTL atrophy &FDG-PET
z Progressive aphasia with marked wordcomprehension deficit
Patient B: Is it just language?
z Impaired on pyramids and palmtrees(80%) and even more on Camel and cacti(60%)
Examples from Camel & Cacti Test Patient B: Is it just language?
z Impaired on pyramids and palmtrees(80%) and even more on Camel and cacti(60%)
z Unusual objects battery: markedimpairment in matching tasks and objectusage
Object Matching and Usage Battery
Recipient Action
Function
Object Matching Tests
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4
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scor
e
patients controls
functionrecipientaction
Real Object Use
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patientscontrols
Naming and Word-to-PictureMatching
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AN JC KH AT D S DC BW JH patientmean
controlmean
namingwpm
Knowledge and Object Use
00.10.20.30.40.50.60.70.80.9
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0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1knowledge
obje
ct u
se
Patient B: Is it just language?
z Impaired on pyramids and palmtrees (80%) andeven more on Camel and cacti (60%)
z Unusual objects battery: marked impairment inmatching tasks and object usage
z Markedly impaired knowledge of object colour
Colouring line drawings...
• 15 SD patients asked tocolour 40 line drawingsof common objects
• Objects includedanimals, fruits andvegetables, body parts,and artifacts withconventional colours
• 2 patients coloured allobjects, the rest pointedto the colours theywould use
Correlation with word-picture matching
Patient C
z 60 months word finding difficulty and “lossof memory for word”
z Marked impairment in comprehension
z Restricted everyday abilities, good withnumbers, able to cook, still driving!
z Strange habits
Patient C: Spontaneous Speech
JH: What kind of job did you do?
Patient: I did things, you know.. In the house
JH: Do you have any hobbies?
Patient: Hobbies, what are they? That’s just myproblem I don’t know words
JH: Things you like to do.
Patient: Oh, I like to play golf.
Patient C: Is she demented?
z Fluency: “what’s an animal”
z Naming: zero
z Word-picture matching: chance
z Pyramids and palmtrees: very poor
z Preserved: digit span, visuospatial skills,recognition memory for pictures
Patients A, B and C are one!
z Patient A = W.M in 1998
z Patient B = W.M. in 2001
z Patient C = W.M in 2003
z Typical longitudinal course in semanticdementia
Change in naming errors
d.k.birdpigeoneagle
creatureaustraliankoalakangaroo
creaturehorse+zebra
creature++horse
+++dog
200320011998
Naming in SD: effects ofdifficulty in patient W.M.
0102030405060708090
100
1998 1999 2000 2001 2002 2003
Naming: easyNaming: hard
Fluency, naming andcomprehension in SD: patient W.M.
0102030405060708090
100
1998 1999 2000 2001 2002 2003
FluencyNamingW-P matching
Comprehension in SD: effects ofstimuli in patient W.M.
30
40
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60
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100
1998 1999 2000 2001 2002 2003
PPT: picturesCCT: picturesSoundsColour knowledge
Progression in semanticdementia
z Fluency and naming low freq and atypicalexemplars. Word definition tests.
z Impairment on comprehension testsrequiring specific “low level” knowledge
z Particular problems where the mapping ofstimulus to meaning is arbitraryy Words ->sounds ->pictures ->objects
What is semantic dementia?
z Insidious onset and gradual progressionz Language disorder characterised by
y Fluent empty spontaneous speechy Loss of word meaning: impaired comprehension and
namingy Semantic paraphasias
z Perceptual disorder characterised byy Prosopagnosia and/ory Associative agnosia
z Preserved matching and drawingz Preserved single word reading
Longitudinal MRIs in W.M.
16-12-99 18-08-00+246 days
27-06-01+559 days
Neural basis of concept knowledge?
From McClelland and Rogers (2003)
Semantics
Visual VerbalAuditory Haptic
Vision Hearing Touch Taste Smell
• Local reps ofwords
• Local reps ofvisual features
namesdescriptors
A computational implementationA computational implementation
Voxel BasedMorphometryin Semantic dementia
Mummery et al. 2000
VBM Correlation with semantic loss in FTD/SDseries
Semantic and Episodic Memory
SemanticMemory
task
EpisodicMemory
task
-35
-30
-25
-20
-15
-10
-5
0
5
Z-S
core
W M KH AT GCB SL JH DC IF M S FM A M DE
Episodic Memory
Semantic Memory
Patients with Semantic Dementia
Performance of SD Patients
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core
PL IH R W M C VJ V A S C RB HM ATy
Episodic Memory
Semantic Memory
Patients with Alzheimer's Disease
Performance of AD Patients
Temporal source memory testTemporal source memory testStudy Phase 1Study Phase 1
Simons et al. Brain 2002
Study Phase 2Study Phase 2
“Did you see the picture in Set 1, Set 2, or not at all?”
Test PhaseTest Phase
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WM JP SL JC DS WJ JH VP JW IF
Item
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Item Detection: SD cases ranked by severity
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WM JP SL JC DS WJ JH VP JW IF
Sour
ce D
iscr
imin
atio
n
Source discrimination: SD cases ranked by severity
CANTAB PAL task
z Visuospatial Associative memory; subjects must learn location of novelvisual stimuli
z Difficulty increases from 1-2-3-6-8 stimuliz Subjects have 10 chances to learn each problem
0
10
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0 SD fvFTD DAT CON
Group
No
. er
rors
at
6 o
bje
ct s
tag
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Errors at 6 pattern stage of the PAL (Lee et al., 2003)
The circuit of Papez
Thalamus
Hippocampus
Mammillarybody
Medio-dorsal N.
Lateral-dorsal N.Anterior N.
PosteriorCingulate
Entorhinalcortex
NB: each of these nodeshas been implicated ascausing amnesia in focallesion studies
Method
z Regions of interest traced onto3T volumetric MRI.
z FDG-PET co-registered ontoMRI
z CMRglc calculated
z Normalised to cerebellum
z 3-compartment partial volumecorrection
FDG-PET findings in AD and MCI
MCI AD
Early PETchanges
Early pathologicalinvolvement
Mammillary bodies andthalamus
FDG-PET changes in MCI/AD
Hippocampal complex
0.4
0.5
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0.9
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C AD SD C AD SD
* †
* P<0.05 v Controls † P<0.01 v Controls
LeftRight
†
Hippocampal complex in AD and SD
* SPM P(corr)=0.05
FDG-PET FindingsIn series of SD cases
Posterior Cingulate
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C AD SD C AD SD
LeftRight
Posterior Cingulate in AD and SD
† †
Mammillary Bodies
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0.6
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0.7
0.75
0.8
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0.9
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1
Control AD SD
†
Mamillary bodies in AD and SDSummary of metabolicchanges
AD SD
HC HCMB MBThalamus ThalamusPC PCAmygdala Amygdala
Kim GrahamKaralyn Patterson
Jon SimonsPeter NestorRhys Davies Clare Galton
Mieke Verfaeille Tim Rogers
Andy lee