Title: PPA and Semantic Dementia
1PPA and Semantic Dementia
2Picks Disease
- Six patients with language impairment and
temporal lobe atrophy
3Lund-Manchester CriteriaNeurology 1998 51
1546-1554
- Frontotemporal Lobar Degeneration
- Frontal variant FT dementia
- Progressive nonfluent dsyphasia
- Semantic Dementia
wide range of neuropathological entities
4- FvFTD
- Best viewed in terms of known frontal lobe
symptomatology
5- Orbitobasal disinhibition, poor impulse,
antisocial
6- Medial frontal-cingulate apathy (although very
common in AD) - Dorsolateral disorders of executive function
7Distinguishing FTD from ADPhonology,syntax and
grammar well preserved in AD
- Stereotypical behaviours
- Change in food preferences, Kluver-Bucy like
behaviour - NPI
- PPA phonemic paraphasias are common, rare in AD
- phonemic or literal paraphasias, in which the
response differs from the correct word by one
letter or sound, such as saying "shammer" for
"hammer."
8Semantic Dementia (Snowden 1989)
- Semantic memory (Warrington 1975)
- Term applied to the component of long-term memory
which contains the permanent representation of
our knowledge about things in the world facts,
concepts and words - Culturally shared, acquired early in life.
9Wernickes area
- Gateway for linking the sensory patterns of words
to the distributed associations that encode their
meaning.
10Semantic Dementia (Snowden 1989)
- Affects fundamental aspects of language, memory
and object recognition.
11Semantic Framework
Verbal access
Visual access
Multi-modal semantic system common knowledge
Sounds, smells, tactile
Actions Real object use
12Semantic Dementia
- Progressive anomia, not an aphasia, but a loss of
semantic memory. - Impaired naming, word comprehension, object
recognition and understanding of concepts. - characterized by preserved fluency and impaired
language comprehension phonologically and
syntactically correct
13Assessement
- Category fluency
- Generation of definitions
- Lion it has little legs and big ears, they
sleep a lot, see them in shops - Word-picture matching
- Famous faces test
- Normal episodic memory, normal visuospatial
skills
14- Nature of errorSemantic-type naming
errorsinitially within-category, elephant for
hippopotamus, then superordinate dog for
everything, then animal - Profound and complete anomia
- Circumlocutions and semantic paraphasias
- semantic paraphasias, in which the wrong word is
produced, one that is usually related to the
target (eg, "pliers" for "hammer").
15- Nature of errorImpaired general knowledge
patients complain of memory loss. - Whats your favourite food?-
- food, food, I wish I knew what that was.
- Patient JL, aged 60, company director
- frightened by a snail in his backyard, and
thought a goat a strange creature.
16- Phonology and syntax striking preserved
- Surface dyslexia difficulty reading and spelling
irregular words eg Reading PINT to rhyme with
flint, mint etc
Loss of semantic support necessary for correct
pronunciation, creating a phonologically
plausible error( regularization Error)
17SD and memory
- Can relate details ( in a rather anomic fashion)
of recent events, but there is impaired recall of
distant life events.
18Memory what we know
- Patients with lesions to the hippocampus and
related structures show severe impairments to new
learning and a temporally limited retrograde
amnesia.
19- What about patients who may show the converse
neuroanatomical lesion (i.e., focal damage to the
temporal neocortex sparing the hippocampal
system)?
20- What about patients who may show the converse
neuroanatomical lesion (i.e., focal damage to the
temporal neocortex sparing the hippocampal
system). - show the converse pattern of memory impairment,
that is to say, preservation of recent and loss
of distant memories.
21SD and memory
- SD can relate details ( in a rather anomic
fashion) of recent events, but there is impaired
recall of distant life events. - Alzheimer's disease more typical temporally
graded loss (poor recall of recent memories)
22Amnesic Alzheimer's disease patient with
hippocampal atrophy (H) accompanied by a mild
degree of general neocortical atrophy.
23 - R. B., who had bilateral lesions limited to the
CA1 region of the hippocampus although he showed
a relatively severe anterograde memory
impairment, R. B. demonstrated a retrograde
amnesia of no more than 1 or 2 years.
24Semantic dementia patient with severe focal
atrophy of the left temporal lobe see arrow,
right-hand side of MRI scan) involving the pole,
inferior, and middle temporal gyri with relative
sparing of the hippocampal complex (H) and of
the superior temporal gyrus.
25SD
- In most cases, neuroradiological studies reveal
selective damage to the inferolateral temporal
gyri(inferior and middle) of one or both temporal
lobes, with sparing of the hippocampi,
parahippocampal gyri, and subiculum. - Note AD inferior and middle temporal gyri
26Disrupted temporal lobe connections in SD
Mummery CJ et al. Brain 1999, 122 61-73
- PPT SEMANTIC TASK VISUAL TASK
- COWhorsebear. CUCUMBERtomatocorn
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28SD Reduced activity in Left inferior temporal
gyrus (BA 37) Known for specific naming
deficits or anomia Region is presumed to be
structurally intact, but functioning abnormally
due to reduced input from anterior temporal
lobe.
29Temporal lobe regions engaged during normal
speech comprehension Crinion JT et al.Brain,
Vol. 126, No. 5, 1193-1201, May 2003
- Processing of speech is obligatory!
- Aphasic stroke patients importance of the
posterior temporal and inferior parietal cortex. - SD anterior and ventral temporal lobe cortex may
be central to word comprehension -
30Experiment
- Reversed versions of the narratives, (same
acoustic complexity as forward speech) expected
to control for early acoustic processing of the
speech signal in both left and right superior
temporal cortex. - Contrastspeech comprehension
31Results
- Comprehension is dependent on anterolateral and
ventral left temporal regions.
32Patient with SD
33- M. put orange juice in his lasagna and on another
occasion, brought the lawnmower up to the
bathroom when he was asked for a ladder
34Test autobiographical information (e.g., an
event that occurred at secondary school) across
three life periods childhood, early adulthood,
and recent life
- Graham KS Hodges JR. Neuropsychology. 1997 Vol.
11, No. 1, 77-89Differentiating the Roles of the
Hippocampal Complex and the Neocortex in
Long-Term Memory Storage
35- The results suggest that the preservation of
recently acquired autobiographical memories is
restricted to the most recent 5 years, and, in
particular, one patient, only from the last 1 1/2
years. - Medial temporal lobe structures do not store or
index memories for long periods of time, for
example, decades.
36SD and memory
- In contrast to the time-limited role played by
the hippocampus, a crucial site for the storage
of our knowledge of the world and our past
autobiographical experiences is the temporal
neocortex.
37Memory
- As direct connections form within the neocortex,
remembering the experienced event becomes less
dependent on the medial temporal lobe structures
and, therefore, more resistant to hippocampal
damage.
38Memory Hippocampal Function
- Hippocampus does not itself store memories but
acts as an orienting system, flagging the need
for the neocortex to form a new representation (
Alvarez Squire, 1994 ). - Storage of an experienced event as a process
initially reliant on the hippocampal system,
before gradual changes in the neocortex allow the
memory to be stored permanently
39In Alzheimers disease
- Significant episodic memory impairment due to
functional disconnection of hippocampus
40In Alzheimers disease
- Significant episodic memory impairment due to
functional disconnection of hippocampus
(transentorhinal limbic) - Even early, may be significant semantic
impairment due to temporal neocortex involvement. - (NB Category dissasociation natural vs
artefactual)
41Memory
- Temporal memory system for semantic facts, and
medial memory system for episodic memories is an
oversimplification. - Neuropsychologia 2002
- Snowden JS, Neary D
- Relearning of verbal labels in semantic dementia
42- Semantic knowledge about the world is more than a
static storehouse of words and objects
represented by a set of abstract properties. It
includes personalised, experience-based
knowledge.
43- Descriptive information about the meaning of the
item - The stimulus picture of a duck was the same type
of thing as the china duck ornament in her own
conservatory and the same as the ducks that she
sees on the pond when she walks in her local
park. A line drawing of a rolling-pin was
described as the same sort of object as the long
glass rolling-pin in her kitchen drawer, which
she had used in the past to make pastry to put on
the top of pies.
44- 20 pictures,all of which the patient had
consistently failed to name on the pre-test
assessments. - Recall at 2 weeks and 4 months
45- Episodic memories specific temporal and spatial
context. - Object information, represented by temporal
neocortex, is linked with temporal and spatial
information, represented by other brain regions. - This linking of (weak) word/object information
with (strong) spatial and temporal information
that provides the basis for patients' relative
preservation of autobiographical memories.
46- In semantic dementia the most context-free levels
of knowledge (constituting traditional notions of
semantic memory) are most compromised. - In contrast, patients may retain knowledge tied
to specific experiences or routines
47- Episodes gradually, over many years, take on the
properties of semantic memory (i.e., resemble
general knowledge by becoming independent of
specific temporal and spatial contexts).
48- Butters and Cermak (1986)
- a detailed case study of a patient with
Korsakoff's syndrome, - "knowledge of public events and personal
experiences from the 1930s and 1940s may be part
of semantic memory whereas public and personal
happenings from the past decade may still be
associated with specific spatial and temporal
contexts
49- A more appropriate compartmentalisation might be
between context-free (neocortical) and
context-bound (medial temporal) memories. The
latter is characterised by the drawing together
of distinct aspects of information (item, time,
space) from distant cortical sites and includes
both semantic and episodic characteristics.
50PPA
- "a slowly progressing aphasic disorder without
the additional intellectual and behavioral
disturbances of dementia" - Memory, judgment, executive function intact.
- Mesulam, M. M. (1982). Slowly progressive aphasia
without generalized dementia. Annals of
Neurology, 11, 592-598, and - Mesulam, M.M. (2001). Primary Progressive
Aphasia. Annals of Neurology, 49, 425-432.
51PPA
- 1. Insidious onset and gradual progression of
word-finding, object-naming, or word
comprehension impairments as manifested during
spontaneous conversation or as assessed through
formal neuropsychological testing of language. - 4. Absence of significant apathy, disinhibition,
forgetfulness for recent events, visuospatial
impairment, visual recognition deficits, or
sensorimotor dysfunction within the initial 2
years of illness. - 5. Acalculia and ideomotor apraxia can be present
even in the first 2 years. Mild constructional
deficits and perseveration (eg, as assessed by
the go no-go task) are also acceptable as long as
neither visuospatial deficits nor disinhibition
influence daily living activities.
52Classification?
- Cases of SD often included under PPA When free
of face and object recognition deficits, semantic
dementia constitutes a subtype of PPA with poor
comprehension of verbal semantics. - Annals of Neurology53, 2003. Pages 35-49
- Primary progressive aphasia PPA and the language
network
53PPA vs SD?
- Aphasia in PPA can be fluent
- there is not a single type of language
dysfunction that is pathognomonic for PPA - the term SDdesignates a prominent fluent
aphasia with impaired comprehension in the
presence of of prominent defects of visual
recognition (or perception). - But also used to refer to PPA subtype with fluent
speech and impaired comprehension - Mesulam, M.M. (2001). Primary Progressive
Aphasia. Annals of Neurology, 49, 425-432.
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56Semantic dementia patient with severe focal
atrophy of the left temporal lobe see arrow,
right-hand side of MRI scan) involving the pole,
inferior, and middle temporal gyri with relative
sparing of the hippocampal complex (H) and of
the superior temporal gyrus.
57PPA vs SD?
- Hodges
- SD is fluent, PPA is not
- SD deteriorate fast, PPA slow.
- Primary disorder is verbal, visual component is
not obligatory (visuospatial tests are normal)
58Brocas
- Generation of articulatory sequences so that
thoughts can be turned into statements with
correct phonology and syntax. - Dysfunction leads to impaired articulation, word
order, grammar. - Phonology sound structure
- Syntax sentence order and structure
59PPA
- Anomia is (nearly) universal in PPA
- Anomia can emerge with either fluent or
non-fluent speech - PPA with agrammatism, frequently impaired
fluency, telegraphic speech - Rare lexical lacunes, which become increasingly
common - school? What does school mean?
60PPA
- Comprehension excellent, except for grammatically
complex sentences the lion was eaten by the
tiger vs the tiger ate the lion - Progress to mutism
61Annals of NeurologyVolume 53, Issue 1, 2003.
Pages 35-49Sreepadma P. Sonty, BA 1, M.-Marsel
Mesulam, MD 1 2 3, Cynthia K. Thompson, PhD 1 2
4, Nancy A. Johnson, PhD 1 3, Sandra Weintraub,
PhD 1 3, Todd B. Parrish, PhD 1 5, Darren R.
Gitelman, MD 1 2 5
- Sample of PPA patients with impaired word finding
but preserved comprehension of conversational
speech
62Annals of NeurologyVolume 53, Issue 1, 2003.
Pages 35-49
- fMRI.
- Judgment of pairs of words
- Phonological task React if words were homonyms
(ie, had identical pronunciation but dissimilar
orthography and meaning). - Semantic taskReact if words in a pair were
synonyms (ie, had a very similar meaning but
dissimilar orthography and phonology).
63Annals of NeurologyVolume 53, Issue 1, 2003.
Pages 35-49
- PPA patients
- Activation in fusiform gyrus, precentral gyrus,
and intra-parietal sulcus. - May be a compensatory spread of language-related
neural activity
64- Word reading is a highly learned, automatic task.
- In PPA, this process may lose its automaticity
and may become increasingly more dependent on
laborious grapheme-to-phoneme transformations,
such as those that are necessary for reading
unfamiliar pseudowords. - .
65PPA Pathology
- 60 neuronal loss with gliosis lacking in
distinctive histopathological features. - 20 Alzheimer's disease.
- Some of these patients have an unusual
perisylvian and temporal neocortical distribution
of neurofibrillary tangles, which occasionally
spares medial temporal lobe structures. - Another 20 show the tau-positive,
intracytoplasmic bodies of Pick's disease.