Stefano F. Cappa Department of Neuroclinical Sciences Vita Salute University and San Raffaele Scientific Institute Milan, Italy
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1 Stefano F. Cappa Department of Neuroclinical Sciences Vita Salute University and San Raffaele Scientific Institute Milan, Italy Declared no potential conflict of interest.
2 CLINICAL HETEROGENEITY Stefano F. Cappa Vita-Salute San Raffaele University and San Raffaele Scientific Institute, Milan, Italy
3 The fronto-temporal spectrum Behavioural variant Progressive aphasia non-fluent/agrammatic variant semantic variant (logopenic-phonological variant) Movement disorder variants FTD-MND CBD-PSP
4 The fronto-temporal spectrum Behavioural variant Progressive aphasia non-fluent/agrammatic variant semantic variant (logopenic-phonological variant) Movement disorder variants FTD-MND CBD-PSP
5 Raskovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, van Swieten JC, Seelaar H, Dopper EGP, Onyike C, Hillis A, Josephs K, Boeve BF, Kertesz A, Seeley WW, Rankin K, Johnson JJ, Gorno- Tempini ML, Rosen H, Neuhaus J, Latham C, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer J, Rossor M, Galasko G, Salmon DP, Black SE, Mesulam M, Weintraub S, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL.
6
7 A comprehensive experimental assessment of social cognition bvftd HC N (males) 13 (10) 39 (30) Mean age (SD) 64 (7) 63 (6) Mean education MMSE Months from onset FBI NPI CDR (range) 0.5-1
8 Story-Based ToM and Empathy Task (STET) CARTOON-TASK: 36 comic strips SECTIONS: Theory of Mind (ToM); Empathy (Emp); Physical causation (Caus) N OF PERSONS: One (ToM1/Emp1/Caus1) or two (ToM2/Emp2/Caus2) SOLUTIONS: socially/emotionally correct; socially/emotionally wrong; completely wrong
9 TOM2
10 EMP2
11 CAUS2
12 Voxel-based morphometric study (11 bvftd 20 HC) Overall gray matter density reduction in bvftd Correlations between STET and gray matter density Whole Brain ROIs
13 Behavioural results p < 0.05 p < HC bvftd p < 0.02
14 p =0.055
15 bvftd vs HC p < 0.05 corrected
16 Whole Brain and ROIs EMP and TOM p<0.05 corrected p<0.05
17 Whole Brain CAUS p<0.05 corrected
18 Whole Brain and ROIs EMP p<0.05 corrected p<0.05
19 Interpersonal Reactivity Index (IRI) (18 HC, 23 bvftd, 14 AD) Phantasy, Perspective Taking, Empathic consideration bvftd < HC and AD (p < 0.001) Personal distress inverse effect in bvftd (p > 0.05) ** ** **
20 Self-Monitoring Scale (SMS) (18 HC, 23 bvftd, 14 AD) bvftd < HC and AD (F = 18.43; p < ) ** Social Norms Evaluation (102 HC, 23 bvftd, 16 AD) bvftd < HC and AD (F=23.98; p < ) **
21 Ultimatum Game Test (71 HC, 15 bvftd) bvftd mare refusals than HC for all conditions except 5-5 (p < 0.05) bvftd HC M-W U test (valore p) Offerta 1 7 % 37 % Offerta 2 9 % 42 % Offerta 3 7 % 47 % Offerta 4 24 % 59 % Offerta 5 96 % 98 % Offerte Eque (4/5 ) 76 % 87 % Offerta Inique (1/2/3 ) 7 % 42 %
22 The fronto-temporal spectrum Behavioural variant Progressive aphasia non-fluent/agrammatic variant semantic variant (logopenic-phonological variant) Movement disorder variants FTD-MND CBD-PSP
23 Pick, 1892 Lund, Manchester Mesulam, 1982
24
25
26 Gorno Tempini et al., 2004
27 Agosta et al., submitted
28
29 Minimal assessment Quantitative/qualitative production analysis Single word naming and comprehension Sentence repetition Syntactic comprehension
30 Articulation Naming Word comprehension Repetition Syntactic comprehension NFPA impaired impaired- PP preserved impaired impaired SD preserved impaired- SP impaired preserved rel. preserved LPA preserved (slowhesitant) impaired- PP preserved impaired impaired
31 Right temporal variant of semantic dementia Presentation with visuo-perceptual impairment (often prosopoagnosia) Progression to widespread semantic dysfunction Differential diagnosis with posterior cortical atrophy and Lewy body dementia
32 The fronto-temporal spectrum Behavioural variant Progressive aphasia non-fluent/agrammatic variant semantic variant (logopenic-phonological variant) Movement disorder variants FTD-MND CBD-PSP
33 FTD-MND MND/dementia: usually bvftd MND/aphasia: usually non-fluent/agrammatic Cognitive disorders in non-demented MND patients
34 CB-PSP syndrome Very low correlation with CBD pathology (Ling et al., 2010) At the clinical level, there is a huge overlap between the CB and PSP phenotype A careful examination of praxis is required
35 Conclusions A correct definition of the clinical phenotype requires an in-depth evaluation based on neuropsychology and neuroimaging The clinical phenotype reflect exclusively the topography of brain involvement by the pathological process The relationship between the clinical and imaging phenotype is only probabilistic
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