Transcript PPA and Semantic Dementia

PPA and Semantic Dementia
Pick’s Disease
• Six patients with language impairment
and temporal lobe atrophy
Lund-Manchester Criteria
Neurology 1998: 51: 1546-1554
• Frontotemporal Lobar Degeneration
– Frontal variant FT dementia
– Progressive nonfluent dsyphasia
– Semantic Dementia
wide range of
neuropathological entities
• FvFTD
• Best viewed in terms of known frontal
lobe symptomatology
• Orbitobasal: disinhibition, poor
impulse, antisocial
• Medial frontal-cingulate: apathy
(although very common in AD)
• Dorsolateral: disorders of executive
function
Distinguishing FTD from AD
Phonology,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."
Semantic 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.
Wernicke’s area
• Gateway for linking the sensory
patterns of words to the distributed
associations that encode their
meaning.
Semantic Dementia (Snowden 1989)
• Affects fundamental aspects of
language, memory and object
recognition.
Semantic Framework
Visual access
Verbal access
Multi-modal semantic system
=“common knowledge”
Actions
Real object use
Sounds, smells, tactile
Semantic 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”
Assessement
• 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
• Nature of error
Semantic-type naming errors:initially withincategory, “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").
• Nature of error
Impaired general knowledge; patients
complain of memory loss.
• “What’s 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.
• 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)
SD and memory
• Can relate details ( in a rather anomic
fashion) of recent events, but there
is impaired recall of distant life
events.
Memory: what we know:
• Patients with lesions to the
hippocampus and related structures
show severe impairments to new
learning and a temporally limited
retrograde amnesia.
• What about patients who may show
the converse neuroanatomical lesion
(i.e., focal damage to the temporal
neocortex sparing the hippocampal
system)?
• 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.
SD 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)
Amnesic Alzheimer's disease patient with hippocampal
atrophy (H) accompanied by a mild degree of general
neocortical atrophy.
• 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.
Semantic 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.
SD
• 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
Disrupted temporal lobe connections in SD
Mummery CJ et al. Brain 1999, 122: 61-73
• PPT: SEMANTIC TASK
VISUAL TASK
• COW;horse;bear. CUCUMBER:tomato;corn
SD
: 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.
Temporal 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
•
Experiment
• 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.
• Contrast=speech comprehension
Results
• Comprehension is dependent on
anterolateral and ventral left
temporal regions.
Patient with SD
A. 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
Test: 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, 77-89
Differentiating the Roles of the Hippocampal Complex and the Neocortex in
Long-Term Memory Storage
• 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.
SD 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.
Memory
• 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.
Memory: 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
In Alzheimer’s disease
• Significant episodic memory
impairment due to functional
disconnection of hippocampus
In Alzheimer’s 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)
Memory
• 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
• 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.
• 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.
• 20 pictures,all of which the patient
had consistently failed to name on the
pre-test assessments.
• Recall at 2 weeks and 4 months
• 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.
• 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
• 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).
• 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”
• 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.
PPA
• "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.
PPA
• 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
Classification?
• 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 Neurology
53, 2003. Pages: 35-49
• Primary progressive aphasia: PPA and the language
network
PPA vs SD?
• “Aphasia in PPA can be fluent”
• “ there is not a single type of language
dysfunction that is pathognomonic for PPA”
• “the term SD…designates 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.
Semantic 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.
PPA 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)
Broca’s
• 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
PPA
• 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?”
PPA
Comprehension excellent, except for
grammatically complex sentences: “
the lion was eaten by the tiger” vs
“the tiger ate the lion”
Progress to mutism
Annals of Neurology
Volume 53, Issue 1, 2003. Pages: 35-49
Sreepadma 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
Annals of Neurology
Volume 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 task:React if words in a pair were
synonyms (ie, had a very similar meaning
but dissimilar orthography and phonology).
Annals of Neurology
Volume 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
• 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-tophoneme transformations, such as those
that are necessary for reading unfamiliar
pseudowords.
• .
PPA 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.