Declared no potential conflict of interest.

Stefano F. CappaDepartment of Neuroclinical SciencesVita Salute University andSan Raffaele Scientific InstituteMilan, Italy

CLINICAL HETEROGENEITY

Stefano F. Cappa

Vita-Salute San Raffaele University and

San Raffaele Scientific Institute,

Milan, Italy

The fronto-temporal spectrum

• Behavioural variant

• Progressive aphasia

• non-fluent/agrammatic variant

• semantic variant

• (logopenic-phonological variant)

• Movement disorder variants

• FTD-MND

• CBD-PSP

The fronto-temporal spectrum

• Behavioural variant

• Progressive aphasia

• non-fluent/agrammatic variant

• semantic variant

• (logopenic-phonological variant)

• Movement disorder variants

• FTD-MND

• CBD-PSP

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.

A comprehensive experimental assessment of social

cognition

bvFTD HC

N (males) 13 (10) 39 (30)

Mean age (SD) 64 (7) 63 (6)

Mean education 11.85 12.28

MMSE 25.33 28.86

Months from onset 52.50 -

FBI 22.08 -

NPI 27.58 -

CDR (range) 0.5-1

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

TOM2

EMP2

CAUS2

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

Behavioural results

HC

bvFTDp < 0.001

p < 0.02

p < 0.05

p =0.055

bvFTD vs HC

p < 0.05 corrected

Whole Brain and ROIs

EMP and TOM

p<0.05 corrected

p<0.05

CAUS

p<0.05 corrected

Whole Brain

p<0.05 corrected

p<0.05

EMP

Whole Brain and ROIs

Interpersonal Reactivity Index (IRI) (18 HC, 23 bvFTD, 14 AD)

Phantasy, Perspective Taking, Empathic considerationbvFTD < HC and AD (p < 0.001)

Personal distress inverse effect in bvFTD (p > 0.05)

** ****

bvFTD < HC and AD (F = 18.43; p < 0.0000)

Self-Monitoring Scale (SMS) (18 HC, 23 bvFTD, 14 AD)

Social Norms Evaluation (102 HC, 23 bvFTD, 16 AD)

bvFTD < HC and AD (F=23.98; p < 0.0000)

**

**

bvFTD mare refusals than HC for all conditions except 5-5 (p < 0.05)

Ultimatum Game Test (71 HC, 15 bvFTD)

bvFTD HC M-W U test

(valore p)

Offerta 1€ 7 % 37 % 0.0105

Offerta 2€ 9 % 42 % 0.0193

Offerta 3€ 7 % 47 % 0.0006

Offerta 4€ 24 % 59 % 0.0090

Offerta 5€ 96 % 98 % 0.5494

Offerte Eque (4/5€) 76 % 87 % 0.0254

Offerta Inique (1/2/3€) 7 % 42 % 0.0068

The fronto-temporal spectrum

• Behavioural variant

• Progressive aphasia

• non-fluent/agrammatic variant

• semantic variant

• (logopenic-phonological variant)

• Movement disorder variants

• FTD-MND

• CBD-PSP

Pick, 1892Lund, Manchester1987-89

Mesulam, 1982

Gorno Tempini et al., 2004

Agosta et al., submitted

Minimal assessment

• Quantitative/qualitative production analysis

• Single word naming and comprehension

• Sentence repetition

• Syntactic comprehension

Articulation Naming Word

comprehension

Repetition Syntactic

comprehension

NFPA impaired impaired-

PP

preserved impaired impaired

SD preserved impaired-

SP

impaired preserved rel. preserved

LPA preserved

(slow-

hesitant)

impaired-

PP

preserved impaired impaired

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

The fronto-temporal spectrum

• Behavioural variant

• Progressive aphasia

• non-fluent/agrammatic variant

• semantic variant

• (logopenic-phonological variant)

• Movement disorder variants

• FTD-MND

• CBD-PSP

FTD-MND

• MND/dementia: usually bvFTD

• MND/aphasia: usually non-fluent/agrammatic

• Cognitive disorders in non-demented MND patients

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

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