Frontotemporal lobar degeneration:
demographic and clinical characteristics
in a Turkish dementia population
Görsev G. Yen...
FTLD Prevalence
 Not clear (4-16%)
 Common cause pre-senile dementia
1:1 with AD 45-64 years
 (Ratnavalli Neurology 20...
FTLD in Izmir, Turkey
Demographic data
Genetics/Pathological Syndrome
Neary Criteria – FTD, PA, SD
MND association
 1994-2004 Izmir DEU Dementia Clinic
N=1169
 Demented= 66 %
AD (possible / probable) 67 %
Vascular dementia 15 %
Fron...
FTLD Clinical Heterogeneity
 Genetic & sporadic cases
 Histology varies
 Motor overlap with PSP, CBD, ALS
Neary Criteria
 Frontotemporal Lobar Degeneration
 Frontotemporal Dementia
 Progressive Non-Fluent Aphasia
 Semantic D...
Dokuz Eylül University
Dementia and Movement Disorders Clinics
 1994-2001
 35 FTLD, 25 PSP, 5 CBD cases
 Demographic an...
FTLD: Gender
**
Turkish (N=35) (% male)
Age(Years)
**
39%
40%
72%
59%
0
20
40
60
80
FTD SD PNFA MND
40%
67%
64%
0
20
40
60...
FTLD: Age at Onset
**
58
59
63
50
55
60
65
FTD SD PNFA
US (N=353)
Age(Years)
Johnson et al. Arch Neurol. 2005;62:925-930.
...
Presenile onset (%) -Turkish
26%
100%
48%46%
0
20
40
60
80
100
FTLD
(N=
35)PSP
(N=
25)CBD
(N=
5)AD
(N=
390)
**
40-60 %
In Netherland series 38%
(15 million screened)
Family Hx (+) , RR=3.5
Family history
Family Hx (%)-Turkish population
10%
24%20%
25%
54%
0
0
0
0
0
1
1
FTLD
(N=
35)
PSP
(N=25)CBD
(N=5)
AD
(N=
390)
VAD
(N=65)
...
FTLD Pathological Syndrome
Core Features
Frontotemporal predominance
Gliosis, spongiosus, neuronal loss
Variable Histological Features
Neuronal inclusions with ubiquitin
 (Clinical: MND, ALS, Paget, Inclusion body myositis)
...
Pick Bodies Cerebral cortex
(Described by Alzheimer in 1911)
Time (minutes)
Distance
travelledbythe
tauspecies(m)
B.A.
d
0
20
40
60
80
100
0N4R-EGFP
0N4RpCIneo
0N4R-EGFP
0N4R-untagge...
Tau mutations
Bigio, et al, 2004, J Neuropath Exp Neurol, 63(8): 801 811
Neuronal ubiquitinated intranuclear
inclusions in familial and ...
FTD with ubiquitinated
neuronal inclusions and
visuospatial impairment
Meiner et al Neurology 2005;65:478–480
Ubiquitin and Tau
 Ubiquitin is a marker for a
given protein to be sent to a
proteasome for degradation
 Ubiquitin prote...
FTD Neuropathology Subtypes
 FTD-Ub related to MND subtype
 CBD, PSP major tau subtype
 DLDH less common with new
stain...
Clinical Features
 Subtypes
 MND
 Parkinsonism
 MMSE
FTLD subtypes in the US and Turkey
PNFA
(n=11)
31%
SD (n=3)
9%
FTD
(n=21)
60%
PNFA
(n=87)
25%
SD
(n=66)
19%FTD
(n=200)
56%...
MND and FTD are associated
 FTD is associated with MND (15%)
 Most ALS patients develop FTD
 FTLD-ALS chr 9 and 17
 Hy...
Chang et al, Neurology 2005;65:75–80
Brain atrophy in ALS and ALS/FTLD
FTLD ;
78%
FTD_MND
; 22%
0%
10%
20%
30%
40%
50%
60%
70%
80%
FTLD FTD_MND
Turkish FTLD and MND
Webster scores-Turkish FTLD subtypes
4,4
0,5
1
0,6
0,00
1,00
2,00
3,00
4,00
5,00
6,00
7,00
8,00
FTD SD PNFA FTD-
MND
Clini...
Clinical Features
 Parkinsonism appears earlier in
FTLD
 MND - more often parkinsonism
 No tau mutation was found in FT...
MMSE Scores in Turkish FTLD
14,1014,10
24,30 23,60
0
20
FTLD PSP CBD MND-FTD
MMSE Figure copying (%)
63%
0%
69%
33%
0
20
40
60
80
FTLD
(n=
27)
PSP(n=
25)CBD
(n=
5)
ND-FTD
(n=
8)
Clinical patterns
PSP~CBD
Both higher Webster and MMSE
scores
MMSE figure copy is discriminative
Clinical patterns
Webster scores
FTD-MND > FTLD
MMSE scores
FTD-MND = FTLD
preserved figure copying
FTD-MND > FTLD
Clinical patterns
FTLD subtypes
 total MMSE PNFA < SD < FTD
 figure copy SD < PNFA < FTD
Conclusions
 FTLD common in presenile ages
 Turkish FTLD subtypes have similar
profile to the US
FTD> PNFA > SD
Conclusions
 Higher family Hx than other dementias
(54%)
 FTLD-MND association (22%)
 FTD-MND has higher parkinsonism
s...
FTD Turkish characte..
FTD Turkish characte..
FTD Turkish characte..
FTD Turkish characte..
Upcoming SlideShare
Loading in …5
×

FTD Turkish characte..

630 views
466 views

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
630
On SlideShare
0
From Embeds
0
Number of Embeds
3
Actions
Shares
0
Downloads
3
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

FTD Turkish characte..

  1. 1. Frontotemporal lobar degeneration: demographic and clinical characteristics in a Turkish dementia population Görsev G. Yener, M.D. Neurology, Dokuz Eylül University Izmir, Turkey gorsev.yener@deu.edu.tr
  2. 2. FTLD Prevalence  Not clear (4-16%)  Common cause pre-senile dementia 1:1 with AD 45-64 years  (Ratnavalli Neurology 2002) more common than AD below 60 years  (Knopman Neurology 2004)
  3. 3. FTLD in Izmir, Turkey Demographic data Genetics/Pathological Syndrome Neary Criteria – FTD, PA, SD MND association
  4. 4.  1994-2004 Izmir DEU Dementia Clinic N=1169  Demented= 66 % AD (possible / probable) 67 % Vascular dementia 15 % Fronto-temporal dementia 4 % Lewy body dementia 9 %
  5. 5. FTLD Clinical Heterogeneity  Genetic & sporadic cases  Histology varies  Motor overlap with PSP, CBD, ALS
  6. 6. Neary Criteria  Frontotemporal Lobar Degeneration  Frontotemporal Dementia  Progressive Non-Fluent Aphasia  Semantic Dementia Neary et al. 1998, Neurology
  7. 7. Dokuz Eylül University Dementia and Movement Disorders Clinics  1994-2001  35 FTLD, 25 PSP, 5 CBD cases  Demographic and clinical features  Webster  MMSE (subitems)
  8. 8. FTLD: Gender ** Turkish (N=35) (% male) Age(Years) ** 39% 40% 72% 59% 0 20 40 60 80 FTD SD PNFA MND 40% 67% 64% 0 20 40 60 80 FTD SD PNFA US (N=353) (% male) Johnson et al. Arch Neurol. 2005;62:925-930. Yener et al 2002
  9. 9. FTLD: Age at Onset ** 58 59 63 50 55 60 65 FTD SD PNFA US (N=353) Age(Years) Johnson et al. Arch Neurol. 2005;62:925-930. 61 72 61 50 55 60 65 70 75 FTD SD PNFA Turkish (N=35) ? Yener et al 2002
  10. 10. Presenile onset (%) -Turkish 26% 100% 48%46% 0 20 40 60 80 100 FTLD (N= 35)PSP (N= 25)CBD (N= 5)AD (N= 390) **
  11. 11. 40-60 % In Netherland series 38% (15 million screened) Family Hx (+) , RR=3.5 Family history
  12. 12. Family Hx (%)-Turkish population 10% 24%20% 25% 54% 0 0 0 0 0 1 1 FTLD (N= 35) PSP (N=25)CBD (N=5) AD (N= 390) VAD (N=65) **
  13. 13. FTLD Pathological Syndrome Core Features Frontotemporal predominance Gliosis, spongiosus, neuronal loss
  14. 14. Variable Histological Features Neuronal inclusions with ubiquitin  (Clinical: MND, ALS, Paget, Inclusion body myositis) Neuronal inclusions with tau  (Clinical: FTDP-17, PSP, CBD) Other inclusions  (Neuronal intermediate filament inclusion dementia) No inclusions (DLDH)  (Clinical: FTLD)
  15. 15. Pick Bodies Cerebral cortex (Described by Alzheimer in 1911)
  16. 16. Time (minutes) Distance travelledbythe tauspecies(m) B.A. d 0 20 40 60 80 100 0N4R-EGFP 0N4RpCIneo 0N4R-EGFP 0N4R-untagged Courtesy of Tim Hutton, Cambridge, UK
  17. 17. Tau mutations
  18. 18. Bigio, et al, 2004, J Neuropath Exp Neurol, 63(8): 801 811 Neuronal ubiquitinated intranuclear inclusions in familial and non-familial FTD-MND associated with ALS
  19. 19. FTD with ubiquitinated neuronal inclusions and visuospatial impairment Meiner et al Neurology 2005;65:478–480
  20. 20. Ubiquitin and Tau  Ubiquitin is a marker for a given protein to be sent to a proteasome for degradation  Ubiquitin proteins are also needed for the degradation of tau
  21. 21. FTD Neuropathology Subtypes  FTD-Ub related to MND subtype  CBD, PSP major tau subtype  DLDH less common with new staining techniques
  22. 22. Clinical Features  Subtypes  MND  Parkinsonism  MMSE
  23. 23. FTLD subtypes in the US and Turkey PNFA (n=11) 31% SD (n=3) 9% FTD (n=21) 60% PNFA (n=87) 25% SD (n=66) 19%FTD (n=200) 56% Johnson et al. Arch Neurol. 2005;62:925-930. 3 sites (N=353) 1 site (N=35)Yener et al 2002
  24. 24. MND and FTD are associated  FTD is associated with MND (15%)  Most ALS patients develop FTD  FTLD-ALS chr 9 and 17  Hypometabolism in frontal lobes in ALS
  25. 25. Chang et al, Neurology 2005;65:75–80 Brain atrophy in ALS and ALS/FTLD
  26. 26. FTLD ; 78% FTD_MND ; 22% 0% 10% 20% 30% 40% 50% 60% 70% 80% FTLD FTD_MND Turkish FTLD and MND
  27. 27. Webster scores-Turkish FTLD subtypes 4,4 0,5 1 0,6 0,00 1,00 2,00 3,00 4,00 5,00 6,00 7,00 8,00 FTD SD PNFA FTD- MND Clinical Features-Parkinsonism **
  28. 28. Clinical Features  Parkinsonism appears earlier in FTLD  MND - more often parkinsonism  No tau mutation was found in FTD- MND group.
  29. 29. MMSE Scores in Turkish FTLD 14,1014,10 24,30 23,60 0 20 FTLD PSP CBD MND-FTD
  30. 30. MMSE Figure copying (%) 63% 0% 69% 33% 0 20 40 60 80 FTLD (n= 27) PSP(n= 25)CBD (n= 5) ND-FTD (n= 8)
  31. 31. Clinical patterns PSP~CBD Both higher Webster and MMSE scores MMSE figure copy is discriminative
  32. 32. Clinical patterns Webster scores FTD-MND > FTLD MMSE scores FTD-MND = FTLD preserved figure copying FTD-MND > FTLD
  33. 33. Clinical patterns FTLD subtypes  total MMSE PNFA < SD < FTD  figure copy SD < PNFA < FTD
  34. 34. Conclusions  FTLD common in presenile ages  Turkish FTLD subtypes have similar profile to the US FTD> PNFA > SD
  35. 35. Conclusions  Higher family Hx than other dementias (54%)  FTLD-MND association (22%)  FTD-MND has higher parkinsonism scores

×