PPA and Semantic Dementia

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PPA and Semantic Dementia
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Picks Disease

• Six patients with language impairment and
  temporal lobe atrophy

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Lund-Manchester CriteriaNeurology 1998 51
1546-1554

• Frontotemporal Lobar Degeneration
• Frontal variant FT dementia
• Progressive nonfluent dsyphasia
• Semantic Dementia

wide range of neuropathological entities
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• FvFTD
• Best viewed in terms of known frontal lobe
  symptomatology

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• Orbitobasal disinhibition, poor impulse,
  antisocial

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• Medial frontal-cingulate apathy (although very
  common in AD)
• Dorsolateral disorders of executive function

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Distinguishing 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."

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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.

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Wernickes area

• Gateway for linking the sensory patterns of words
  to the distributed associations that encode their
  meaning.

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Semantic Dementia (Snowden 1989)

• Affects fundamental aspects of language, memory
  and object recognition.

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Semantic Framework
Verbal access
Visual access
Multi-modal semantic system common knowledge
Sounds, smells, tactile
Actions Real object use

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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

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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

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• 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").

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• 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.

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• 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)
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SD and memory

• Can relate details ( in a rather anomic fashion)
  of recent events, but there is impaired recall of
  distant life events.

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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.

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• What about patients who may show the converse
  neuroanatomical lesion (i.e., focal damage to the
  temporal neocortex sparing the hippocampal
  system)?

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• 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.

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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)

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Amnesic Alzheimer's disease patient with
hippocampal atrophy (H) accompanied by a mild
degree of general neocortical atrophy.
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• 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.

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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.
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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

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Disrupted 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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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.
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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

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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.
• Contrastspeech comprehension

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Results

• Comprehension is dependent on anterolateral and
  ventral left temporal regions.

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Patient with SD
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• 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

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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, 77-89Differentiating the Roles of the
  Hippocampal Complex and the Neocortex in
  Long-Term Memory Storage

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• 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.

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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.

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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.

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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

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In Alzheimers disease

• Significant episodic memory impairment due to
  functional disconnection of hippocampus

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In 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)

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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

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• 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.

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• 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.

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• 20 pictures,all of which the patient had
  consistently failed to name on the pre-test
  assessments.
• Recall at 2 weeks and 4 months

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• 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.

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• 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

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• 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).

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• 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

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• 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.

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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.

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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 living activities.

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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 Neurology53, 2003. Pages 35-49
• Primary progressive aphasia PPA and the language
  network

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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 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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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.
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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)

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Brocas

• 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

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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?

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PPA

• Comprehension excellent, except for grammatically
  complex sentences the lion was eaten by the
  tiger vs the tiger ate the lion
• Progress to mutism

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Annals 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

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Annals 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).

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Annals 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

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• 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.
• .

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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.