Semantic and frontotemporal dementias

1. Glasgow, November 2009 Semantic and frontotemporal dementias Julie Snowden Cerebral Function Unit Greater Manchester Neuroscience Centre Salford Royal Foundation Trust

3. Historical Background Clinical descriptions 1900s Pathology 1920s Focal cerebral atrophy 1980s Localisationist Holistic Gestalt psychology Specialisation of function Neuropsychology

4. Spatial orientation (mental map) Praxis Alzheimer’s disease (AD) Executive functions Social cognition Parietal Frontal Visual perception Occipital Temporal Language Frontotemporal lobar degeneration (FTLD) Episodic memory (events)

5. Frontotemporal Lobar Degeneration Progressive aphasia Fronto-temporal dementia Semantic dementia

6. Overview of Frontotemporal Lobar Degeneration • Onset in middle years (45-65) • Insidiously progressive • Affects both men and women • High familial incidence • Median duration 8 years (3-20)

8. Clinical features • Few neurological signs  striatal signs but • May be associated with MND • Routine EEG normal • Focal change on structural / functional imaging

9. Frontotemporal dementia • Breakdown in social, interpersonal conduct • Neglect of self-care and responsibilities • Emotional blunting, loss of insight • Repetitive, stereotyped behaviours • Hyperorality, dietary changes

11. Plans/Goals Checking Organisation Attention Abstraction Flexibility New plan

12. Planning Organisation Attention Abstraction Checking Flexibility Inertia/purposeless overactivity Disorganised behaviour Inattentive, distractible Concrete Poor self-monitoring, impaired insight Inflexible Loss of sympathy and empathy

13. Wisconsin Card Sorting Test

14. Weigls blocks Perseverative Dismantling behaviour shape, colour, motif

15. Brixton spatial anticipation test 2 3 4 5 1 6 7 9 10 8 Burgess & Shallice, 1997

16. Picture sequencing Verbal fluency • Animals • “Billy the budgie • and Spot the dog” • F words • “Frank – my brother” Concrete, rule violations

17. Design fluency in FTD novel, abstract, 4-lines Perseverations, rule violations, concrete

19. Dorsolateral Apathy, inertia Blunting Executive impairment severe Phenotypic variation in FTD Orbital Disinhibited, fatuous Executive impairment mild

23. AD copy FTD copy

24. MRI coronals SPECT coronal sagittal FTD

25. MRI coronals SPECT coronal sagittal AD

26. Cognition in FTD and AD

27. Qualitative performance characteristics in FTD • Impulsivity, inattention • Economy of effort, lack of persistence • Concreteness of thought • Perseverative response • Unconstrained by goal – rule violations

30. Non-tau Ubiquitinated neurones microvacuolation Tau Pick bodies in neurones Pick cells Neurofibrillary tangle-like in neurones and glia Frontotemporal lobar degeneration Ubiquitin protein: TDP-43 protein (Arai et al. 2006)

31. Parietal Frontal Occipital Temporal Frontotemporal lobar degeneration (FTLD) Semantic dementia: overview • Circumscribed, multimodal disorder of meaning • Bilateral, often asymmetric degeneration of the anterior temporal lobes -especially inferior temporal gyri • Part of spectrum of FTLD SD

32. Semantic dementia Impaired Word meaning naming comprehension phonology syntax speech fluency Preserved

33. Language Naming “A nice little dog” Superordinate, coordinate, descriptive, omission errors No TOT effect/effortful word search No benefit from phonemic cueing Comprehension “rabbit ..what’s rabbit?” Partial/degraded knowledge Which is the rabbit? X 

34. Impaired Recognition of: faces, objects nonverbal sounds smells, tastes tactile stimuli Perception of sensory stimuli Semantic loss - multimodal Preserved

35. Perceptual matching  Category matching X

36. SD drawing

37. Nature of memory impairment word and object meaning facts, world knowledge memory for autobiographical events Impaired Preserved

38. SEMANTIC DEMENTIA Bilateral temporal lobe atrophy

39. Behaviour in semantic dementia • Narrowed behavioural repertoire • Preoccupations • Personal hobby e.g. painting, dress making • Word and number games, jigsaws, Sudoku • Preference for routine • Clockwatching, time bound More compulsive than frontotemporal dementia

40. Narrowed world view • Self-centredness • Reduced sympathy and empathy

41. Questions • What determines what is lost and retained? • What is the relationship between knowledge in different modalities? – amodal vs. multi-modal models • What is the relationship between knowledge and experience (semantic-episodic memory)?

42. rabbit ? Animal

45. Margaret Thatcher

46. Elvis Presley

47. Famous face and name recognition id = provides identifying information fam = reports familiarity

48. MR and SPECT imaging Left > right Right > left

49. Name and Face Identity % correct Temporal lobe atrophy

50. Name and Face Familiarity % Temporal lobe atrophy