Frontotemporal lobar degeneration: demographic and clinical characteristics in a Turkish dementia...
-
Upload
julius-pillow -
Category
Documents
-
view
231 -
download
0
Transcript of Frontotemporal lobar degeneration: demographic and clinical characteristics in a Turkish dementia...
Frontotemporal Frontotemporal lobar degeneration: lobar degeneration: demographic and clinical characteristics demographic and clinical characteristics
in a Turkish dementia populationin a Turkish dementia population
Görsev G. YenerGörsev G. Yener, M.D., M.D.
NeurologyNeurology, Dokuz Eylül University, Dokuz Eylül University
Izmir, TurkeyIzmir, Turkey
[email protected]@deu.edu.tr
FTLD FTLD Prevalence Prevalence
Not clearNot clear ( (4-4-16%)16%)
Common cause pre-senile dementiaCommon cause pre-senile dementia
1:1 with AD 45-64 year1:1 with AD 45-64 yearss (Ratnavalli Neurology 2002)(Ratnavalli Neurology 2002)
more common than AD below 60 years more common than AD below 60 years (Knopman Neurology 2004)(Knopman Neurology 2004)
FTLDFTLD in Izmir, Turkey in Izmir, Turkey
Demographic Demographic datadata
GeneticsGenetics//Pathological Syndrome Pathological Syndrome
Neary Criteria – FTD, PA, SDNeary Criteria – FTD, PA, SD
MND associationMND association
1994-2004 Izmir DEU Dementia Clinic1994-2004 Izmir DEU Dementia Clinic
N=1169 N=1169
Demented= 66 % Demented= 66 %
AD (possible / probable) 67 % AD (possible / probable) 67 %
Vascular dementia 15 % Vascular dementia 15 %
Fronto-temporal dementia 4 %Fronto-temporal dementia 4 %
Lewy body dementia 9 %Lewy body dementia 9 %
FTLD Clinical Heterogeneity
Genetic & sporadic casesGenetic & sporadic cases
Histology variesHistology varies
Motor overlap with PSP, CBD, ALSMotor overlap with PSP, CBD, ALS
Neary CriteriaNeary Criteria Frontotemporal Lobar DegenerationFrontotemporal Lobar Degeneration
Frontotemporal DementiaFrontotemporal Dementia
Progressive Non-Fluent AphasiaProgressive Non-Fluent Aphasia
Semantic DementiaSemantic Dementia
Neary et al. 1998, NeurologyNeary et al. 1998, Neurology
Dokuz Eylül University Dokuz Eylül University Dementia and Movement Disorders ClinicsDementia and Movement Disorders Clinics
1994-20011994-2001
35 FTLD, 25 PSP, 5 CBD cases35 FTLD, 25 PSP, 5 CBD cases
Demographic and clinical featuresDemographic and clinical features
WebsterWebster
MMSE (subitems)MMSE (subitems)
FTLD: GenderFTLD: Gender
****
TurkishTurkish (N=35) (N=35) (% male)(% male)
Ag
e (
Years
)A
ge (
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
USUS (N=353) (N=353) (% male)(% male)
Johnson et al. Johnson et al. Arch NeurolArch Neurol. 2005;62:925-930.. 2005;62:925-930. Yener et al 2002Yener et al 2002
FTLD: Age at OnsetFTLD: Age at Onset
****
5859
63
50
55
60
65
FTD SD PNFA
US (N=353US (N=353))
Ag
e (
Years
)A
ge (
Years
)
Johnson et al. Johnson et al. Arch NeurolArch Neurol. 2005;62:925-930.. 2005;62:925-930.
61
72
61
50
55
60
65
70
75
FTD SD PNFA
Turkish (N=35)Turkish (N=35)
?
Yener et al 2002Yener et al 2002
Presenile onset (%) -TurkishPresenile onset (%) -Turkish
26%
100%
48%46%
0
20
40
60
80
100
**
40-60 %40-60 %
In Netherland series 38% In Netherland series 38%
(15 million screened) (15 million screened)
Family Hx (+) , RR=3.5Family Hx (+) , RR=3.5
Family historyFamily 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
)
****
FTFTLLD D PathologicalPathological Syndrome SyndromeCore FeaturesCore Features
Frontotemporal predominanceFrontotemporal predominance
Gliosis, spongiosus, neuronal lossGliosis, spongiosus, neuronal loss
Variable Histological FeaturesVariable Histological FeaturesNeuronal inclusions with ubiquitinNeuronal inclusions with ubiquitin
(Clinical: MND, ALS, Paget, Inclusion body myositis)(Clinical: MND, ALS, Paget, Inclusion body myositis)
Neuronal inclusions Neuronal inclusions with tauwith tau (Clinical: FTDP-17, PSP, CBD)(Clinical: FTDP-17, PSP, CBD)
Other inclusionsOther inclusions (Neuronal intermediate filament inclusion dementia)(Neuronal intermediate filament inclusion dementia)
No inclusionsNo inclusions (DLDH) (DLDH) (Clinical: FTLD)(Clinical: FTLD)
Pick Bodies Cerebral cortex(Described by Alzheimer in 1911)
Time (minutes)
Dis
tanc
e tr
avel
led
by th
e ta
u sp
ecie
s (
m)
B.A.
c d
0
20
40
60
80
100
150 175 200 225 250
0N4R-EGFP0N4RpCIneo
0N4R-EGFP0N4R-untagged
Courtesy of Tim Hutton, Cambridge, UK
Tau mutations
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
FTD with ubiquitinated neuronal inclusions and visuospatial impairment
Meiner et al Neurology 2005;65:478–480
Ubiquitin and TauUbiquitin and Tau
Ubiquitin is a marker for a given protein to Ubiquitin is a marker for a given protein to be sent to a proteasome for degradationbe sent to a proteasome for degradation
Ubiquitin proteins are also needed for the Ubiquitin proteins are also needed for the degradation of taudegradation of tau
FTD Neuropathology SubtypesFTD Neuropathology Subtypes
FTD-Ub FTD-Ub related to MND subtyperelated to MND subtype
CBD, PSP major tau subtypeCBD, PSP major tau subtype
DLDH DLDH less common withless common with new stain new staining ing techniquestechniques
Clinical FeaturesClinical Features
SubtypesSubtypes
MNDMND
ParkinsonismParkinsonism
MMSEMMSE
FTLD subtypes in the US and TurkeyFTLD 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. Johnson et al. Arch NeurolArch Neurol. 2005;62:925-930.. 2005;62:925-930.
3 sites (N=353)3 sites (N=353)
1 site (N=35)1 site (N=35)Yener et al 2002Yener et al 2002
MND and FTDMND and FTD are associatedare associated
FTD is associated with MND (15%)FTD is associated with MND (15%)
Most Most ALS ALS patients developpatients develop FTD FTD
FTLD-ALSFTLD-ALS chr chr 9 9 andand 17 17
Hypometabolism in fHypometabolism in frontal rontal lobes in ALSlobes in ALS
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 subtypesWebster scores-Turkish FTLD subtypes
4,4
0,51
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-ParkinsonismClinical Features-Parkinsonism
**
Clinical FeaturesClinical Features
Parkinsonism appears earlier in FTLDParkinsonism appears earlier in FTLD
MND - more often parkinsonismMND - more often parkinsonism
No tau mutation was found in FTD-MND group.No tau mutation was found in FTD-MND group.
MMSE Scores in Turkish FTLDMMSE Scores in Turkish FTLD
14,1014,10
24,30 23,60
0
20
FTLD PSP CBD MND-FTD
MMSE Figure copying (%)MMSE Figure copying (%)
63%
0%
69%
33%
0
20
40
60
80
Clinical patternsClinical patterns
PSP~CBD PSP~CBD
Both higher Webster and MMSE Both higher Webster and MMSE scoresscores
MMSE figure copy is discriminativeMMSE figure copy is discriminative
Clinical patternsClinical patterns
Webster scores Webster scores FTD-MND > FTLDFTD-MND > FTLD
MMSE scoresMMSE scores FTD-MND = FTLDFTD-MND = FTLD
preserved figure copying preserved figure copying FTD-MND > FTLDFTD-MND > FTLD
Clinical patternsClinical patterns
FTLD subtypes FTLD subtypes
total MMSE total MMSE PNFA < PNFA < SDSD < FTD < FTD
figure copyfigure copy SDSD < PNFA < FTD < PNFA < FTD
ConclusionsConclusions FTLDFTLD common in presenile ages common in presenile ages
Turkish Turkish FTLD FTLD subtypes have similar subtypes have similar profile to the USprofile to the US
FTD> PNFA > SD FTD> PNFA > SD
ConclusionsConclusions Higher family Hx than other dementias Higher family Hx than other dementias
(54%)(54%)
FTLD-MND association (22%)FTLD-MND association (22%)
FTD-MND has higher parkinsonism FTD-MND has higher parkinsonism scores scores