PPA and Semantic Dementia

Pick’s Disease

• Six patients with language impairment and temporal lobe atrophy

Lund-Manchester CriteriaNeurology 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

Multi-modal semantic system=“common knowledge”

Visual access Verbal access

ActionsReal 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 errorSemantic-type naming errors:initially 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").

• Nature of errorImpaired 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, 77-89Differentiating 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 living activities.

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

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 NeurologyVolume 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 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 task:React if words in a pair were synonyms (ie, had a very similar meaning but dissimilar orthography and phonology).

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

• 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.

• .

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.