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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
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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
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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
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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%
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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
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Object Matching and Usage Battery
Recipient Action
Function
Object Matching Tests
0
4
8
12
16
20
24
28
32
36
scor
e
patients controls
functionrecipientaction
Real Object Use
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
prop
orti
on
hold movement orientation
patientscontrols
Naming and Word-to-PictureMatching
0
4
8
12
16
20
24
28
32
36
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
1
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
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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
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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
50
60
70
80
90
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
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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
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-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
-35
-30
-25
-20
-15
-10
-5
0
5
Z-S
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
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
WM JP SL JC DS WJ JH VP JW IF
Item
Det
ectio
n
Item Detection: SD cases ranked by severity
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0
0.1
0.2
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0.4
0.5
0.6
0.7
0.8
0.9
1
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
20
30
40
50
60
F
0 SD fvFTD DAT CON
Group
No
. er
rors
at
6 o
bje
ct s
tag
e
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
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Early PETchanges
Early pathologicalinvolvement
Mammillary bodies andthalamus
FDG-PET changes in MCI/AD
Hippocampal complex
0.4
0.5
0.6
0.7
0.8
0.9
1
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
0.8
0.9
1
1.1
1.2
1.3
1.4
1.5
C AD SD C AD SD
LeftRight
Posterior Cingulate in AD and SD
† †
Mammillary Bodies
0.5
0.55
0.6
0.65
0.7
0.75
0.8
0.85
0.9
0.95
1
Control AD SD
†
Mamillary bodies in AD and SDSummary of metabolicchanges
AD SD
HC HCMB MBThalamus ThalamusPC PCAmygdala Amygdala
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Kim GrahamKaralyn Patterson
Jon SimonsPeter NestorRhys Davies Clare Galton
Mieke Verfaeille Tim Rogers
Andy lee