Pavlovi D. et al.

REVIEW ARTICLE
UDC 616.894-07/-08

FRONTOTEMPORAL DEMENTIA
FRONTOTEMPORALNA DEMENCIJA
Dragan M. Pavlovi 1, Aleksandra M. Pavlovi1, Marija Semnic 2, Vojislava Bugarski2
Abstract: Frontotemporal dementias (FTD), or frontotemporal lobar degeneration (FTLD), are the fourth
most frequent dementias with the prevalence of 3-10%. Dominant clinical expression in FTD are changes in
behavior and personality and disorders of language. Also, in some cases there is parkinsonism and/or signs
of motor neuron involvement. Clinically, FTLD includes frontal variant FTD, primary progressive aphasia (PPA), semantic dementia, FTD with motor neuron disease, and hereditary FTD with parkinsonism
linked to chromosome 17q21.1 (FTDP-17) and corticobasal degeneration (CBD). Heredity is positive in
50% of cases. The age of onset in FTD is from twenties do nineties with mean of 59 years. Disease duration
may range from several months to more than 17 years, most frequently 8 to 10 years. Histopathologically, there are: FTD with tau-positive inclusions (FTD-tau), FTD with tau-negative, ubiquitin positive inclusions (FTD-U) and FTD without inclusions. Almost all FTD are TAR-DNA-binding protein 43 (TDP-43)
proteinopathies or tauopathies. Currently, there is no cure for this disease and the therapy is only symptomatic. As there are serotonergic and dopaminergic deficits in FTD, drugs that enhance the neurotransmission
of these substances are of a potential, but yet not proven benefit. Acethylcholinesterase inhibitors show some
promise. There are several potential targets for therapy of FTD but no studies have been published yet.
Key words: Frontotemporal dementias, clinical classification, diagnosis, therapy
Saetak: Frontotemporalne demencije (FTD) ili frontotemporalna lobarna degeneracija (FTLD) su
etvrti po uestalosti uzrok demencija sa prevalencom od 3-10%. Klinikom slikom FTD dominiraju
promene u ponaanju i linosti, kao i poremeaji govora. Takoe, u nekim sluajevima mogu da se jave
parkinsonizam i/ili znaci oteenja motoneurona. Kliniki, FTLD ukljuuje frontalnu variantu FTD,
primarnu progresivnu afaziju (PPA), semantiku demenciju, FTD sa boleu motoneurona i hereditarnu
FTD sa parkinsonizmom povezanu za hromozomom 17q21.1 (FTDP-17) i kortikobazalnu degeneraciju
(CBD). Naslee je pozitivno u oko 50% sluajeva. Vreme nastanka FTD varira od dvadestih do devedesetih
godina, prosean uzrast je oko 59 godina. Tok bolesti varira od nekoliko meseci do vie od 17 godina,
najee 8 do 10 godina. Histopatoloki postoje: FTD sa tau-pozitivnim inkluzijama (FTD-tau), FTD
sa tau-negativnim, ubikvitin pozitivnim inkluzijama (FTD-U) i FTD bez inkluzija. Skoro sve FTD su
TAR-DNA-binding protein 43 (TDP-43) proteinopatije ili tauopatije. Trenutno nema leenja bolesti i
terapija je samo simptomatska. Kako su neurotransmiterski deficiti u FTD dominantno dopaminergiki
i serotoninergiki, lekovi koji poboljavaju ovu neurotransmisiju su potencijalno korisni ali jo nedostaju
dokazi. Inhibitori acetilholinesteraze su primenjivani u pilot studijama sa izvesnim efektom. Ima nekoliko
potencijalnih ciljeva terapije FTD ali jo nijedna studija nije publikovana.
Kljune rei: Frontotemporalna demencija, klinika klasifikacija, dijagnoza, terapija

Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Ser-

bia
2 Neurology Clinic, Clinical Center of Vojvodina, School of Medicine, University of Novi Sad, Novi Sad,
Serbia
Correspondence to: DM Pavlovi, Neurological Clinic, Clinical Center of Serbia, Belgrade,
Dr Subotia 6, 11000 Belgrade, Serbia., Email: dpavlovic53@hotmail.com
* Received December 20, 2010; accepted February 16, 2011.
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Pavlovi D. et al.

INTRODUCTION

tant biological function. TDP-43 proteinopathies

include FTD-U, FTD-MND and MND (8).

Frontotemporal dementia (FTD), or frontotemporal lobar degeneration (FTLD), is the fourth

most frequent cause of dementia with prevalence
of 3-10% among patients with all types of dementia and are the second most frequent among those
with presenile onset (1). Dominant clinical expression in FTD are changes in behavior and personality and disorders of language. In some FTD subtypes there is parkinsonism and/or signs of motor neuron involvement. Classification of FTLD
includes Picks disease, frontal variant FTD, primary progressive aphasia (PPA), semantic dementia, FTD with motor neuron disease (FTD-MND)
and hereditary FTD with parkinsonism linked to
chromosome 17q21.1 (FTDP-17), corticobasal degeneration (CBD), and some other diseases (2-4).
Risk factors are familial occurrence of APOE 4,
brain injury and thyroid disease. The common
final path of all causes would be the cythoskeletal impairment with consecutive neuronal lesion
and disturbance of dopaminergic and serotonergic transmission (4).
The age of onset of FTD is from twenties do nineties with mean of 59 years. Disease course is unpredictable, as it may range from several months
to more than 17 years, most frequently 8 to 10
years (5). Dementia can remain focal for long periods, but in the majority of cases the pathological process spreads with signs of generalized cognitive impairment. Three main varieties are FTD
in the narrow sense, primary progressive nonfluent aphasia and semantic dementia (6).

MOLECULAR PATHOLOGY
There are three histopathological types of FTLD
(7): FTD with tau-positive inclusions (FTD-tau),
FTD with tau-negative, ubiquitin positive inclusions (FTD-U) and FTD without inclusions. Almost all FTDs (95%) are TAR-DNA-binding
protein 43 (TDP-43) proteinopathies, or tauopathies, and histopathologicaly around 50% of FTDs
are FTD-U (4). Presence of TDP-43 in a substantial portion of FTD, sporadic and hereditary, justifies their inclusion in a separate group of proteinopathies. This protein seams to have an impor14

First known FTD with well defined mutations

were in microtubule (MT) associated protein tau
(MAPT) gene on chromosome 17 with FTD-tau
pathology (9) and progranuline (GRN) gene on
chromosome 17 with FTD-U pathology (10,11).
The main ingredient of the majority of ubiqitinepositive inclusions is TDP-43 as well as in MND
(12). Mutations in GRN are present in 5-10% of all
FTD, 13-25% of familial forms and around 25% of
those with FTD-U pathological finding (13). Reduces expression of progranuline in GRN mutations can stimulate the aberrant metabolism
of TDP-43 (14). Another protein, fused in sarcoma (FUS), was recently found in tau-negative
ubiquinated inclusions and classified as FTD- FUS
(15,16). Apolipoprotein epsilon 4 (apoE4) allele in
fvFTD favors more pronounced brain atrophy in
the frontal lobes (17).

HISTOPATHOLOGY OF FTD
Histopathologically, the most important findings
in FTD are synaptic degeneration, glyosis and
neuronal loss (18). In FTD with behavioral changes (frontal variant FTD - fvFTD), the first changes are observed in the dorsomedial frontal cortex, anterior cingular area and posterior orbitofrontal cortices and frontoinsula. Next, the changes
spread to the anterior insula, anterior cingular cortex, ventral striatum, medial thalamus and frontopolar cortex (19). Semantic dementia is characterized by earliest histopathological findings in the
temporal pole, spreading then to the ventral anterior insula, while in PPA the brunt of changes is
seen in the dominant dorsal anterior insula. In all
types of FTD there are changes in the third and
fourth cortical layer of frontal and temporal cortices (20). Pathological processes can further spread
to the dorsolateral frontal cortex and temporal areas that subserve emotions and semantics.
Patients with FTD-tau more frequently than other subtypes present with visuospatial changes and
extrapyramidal impairments and dysexecutive
symptoms (21). Tau-negative FTD has more pronounced alterations in behavior, social skills and

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Pavlovi D. et al.

verbally-mediated executive skills (21), as well as

decline in personal hygiene (22).

CLINICAL CLASSIFICATION
There are four basic variants of FTLD: 1. FTD, 2.
Progressive aphasia, 3. FTD-MND, and 4. CBD
(23). FTD can further be divided in asymmetric
variants, according to neuropsychological findings, frontal (fv) with behavioral changes and
temporal (tv) FTD (both left and right), and FTD
with parkinsonism. Progressive aphasia can be divided into PPA and semantic dementia. Spreading
of the pathological process can lead to broadening
of the clinical picture finally encompassing both
behavioral and language difficulties. In the leftsided process language disturbances are the most
prominent, in the right-sided process the disinhibition is the most obvious clinical problem while
in bilateral cases the most prominent is dysexecutive syndrome. In fvFTD and PPA there are often GRN mutations, some of which can lead to extrapyramidal signs of CBD syndrome but rarely to
MND (24). On the other hand, MAPT mutations
frequently show semantic dementia and MND.
Frontal (behavioral) variant FTD. Behavioral
changes are the main characteristic of this FTD
type. Clinical manifestations are disinhibition, irritability, aggression, hypersexuality, apathy, aspontaneity, neglect of personal hygiene, mental rigidity, perseverativeness, hyperorality, utilization
behavior, speech and behavior stereotypes (25,26).
Personality changes in fvFTD are loss of insight,
inappropriate jokes (Latin = Moria; German =
Witzelzucht), impaired judgment, loss of empathy,
but unlikely psychotic manifestations (25). Disturbances of emotional regulation are depression, apathy, affect instability, anxiety, irritability and euphoria (27). In different stages the prevalence of
depression in fvFTD is about 40% (25). Differential diagnosis of depression and early fvFTD is difficult because of frequent apathy and dysexecutive syndrome that mimic depression. Depression
in fvFTD is classified in three subtypes: 1. classical
major depression; 2. affective reactibility and labil-

ity that are environment-dependent; and 3. pronounced apathy (pseudodepression) (25).

Social and moral impairment are connected with
dysfunction of the right ventromedial cortex, orbitofrontal cortex and amygdala (23). Some patients change eating habits and some abuse alcohol or cigarettes. Apathy is the most frequent first
symptom of fvFTD that also develops in the majority through the course of the disease and correlates with hypoperfusion in the orbitofrontal and
anterior cingulate cortices (23). Impulsivity and
disinhibition correlate with the right frontotemporal cortex. Motor phenomena comprise primitive reflexes, extrapyramidal changes, and rarely signs of MND. Among cognitive disturbances
the most frequent are dysexecutive syndrome and
speech disturbances that are mostly of the nonfluent type. Perseverations and echolalia are also
frequently present. Sometimes there are memory
problems of the frontal type.
Classical neuropsychological testing is not always helpful. Some patients fail executive functions tests, but some do not. Recognition of facial
emotions, especially negative ones as rage, disgust,
fear and depression is disturbed (28). They more
frequently fail the Theory-of-Mind tests (faux pas
and eyes expressions) and recognition of prosody.
Lack of empathy correlates with the degree of atrophy of the right temporal pole, nucleus caudatus
and gyrus subcalosus but some patients with fulfilled criteria for fvFTD have normal pathohistological findings.
Primary progressive nonfluent aphasia. Primary progressive nonfluent aphasia is isolated disturbance of language functions where global dementia develops only in the late stages and patients can function independently for long periods
(29). The first symptom is anomia in the presenile period, followed by difficulties of the semantic, phonological and syntactic type, both in oral
and written language. Primary progressive fluent
aphasia is a separate entity called later semantic
dementia (30). Except in FTD, PPA syndrome can
be the expression of Alzheimers disease, CBD and
Creutzfeldt-Jakob disease (16). Primary progressive nonfluent aphasia is similar to Brocas aphasia or transcortical motor aphasia with nofluent,
anomic, agrammatic speech, dysarthria, and prob-

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Vujisi at al.

lems in understanding complex sentences (30,19).

Lesions are found in the dominant frontal operculum and the dorsal anterior insula. Nonaphasic
changes can also occur with behavioral problems
such as apathy, irritability, judgment disturbances,
aggressiveness and hyperorality, extrapyramidal
signs and signs of MND. Episodic memory is preserved as well as visuospatial functions and activities of daily living. There are impairments already
on the early acoustic perception level, then on
aperceptive and finally associative level. The process of PPA lasts more than 10 years. Neuroimaging shows focal atrophy of the dominant frontal
lobe.
Semantic dementia. Semantic dementia looks like
fluent aphasia with pronounced anomia, poor understanding of word meaning with better understanding of sentences. Neuropsychological testing
shows dissolution of semantics in the early disease,
then meaning of objects, emotions and finally behavioral disturbances (19). They manifest selective problems of semantic memory, poor category
fluency, reduction of general knowledge, and surface dyslexia (31). The pathological process starts
in the dominant temporal pole and the amygdala
and then spreads to the neighboring frontoinsular,
cingulate and posterior temporal cortex as well as
to the ventral striatum (19). Patients are independent.
Primary progressive prosopagnosia. Primary
progressive prosopagnosia is a rare FTD, corresponding to semantic dementia but with pathology in the nondominant temporal lobe (32). Patients have progressive difficulties in recognizing
familiar faces, first visually and then also by voice,
gait, etc. Other cognitive skills are preserved, except in rare instances of object agnosia.
Hereditary FTD with parkinsonism linked to
chromosome 17. This FTD is also a heterogeneous group of diseases with many mutations of
tau protein gene on chromosome 17q21-22 dominant heredity and on MAPT gene and with presenile onset (4). There is a substantial variability
of this disease both pertaining the phenotype and
genotype. Characteristics are behavioral changes,
cognitive decline and motor phenomena. These
patients are often disinhibited, sometimes apathetic and neglect personal hygiene. They can also
16

show impairment of judgment, aggressiveness,

stereotypical behavior and even auditory hallucinations and paranoid delusions. Neuropsychological changes include dysexecutive syndrome, dysphasia to the degree of mutism in the end stage
with spreading of cognitive decline to the level of
global dementia. Parkinsonism is often present in
the later course of the disease with bradikynesia,
rigidity and postural instability and sometimes
there is also a pyramidal lesion. Typical duration
of FTDP-17 is 10 to 12 years (33).
Frontotemporal dementia with MND. FTDMND is a rare disorder with onset in forties, more
frequent in males and with short duration of only
2 to 3 years (34). This is a sporadic disease but
there are also familial cases all around the world
and it is endemic in Marian Islands and Guam in
West Pacific. In a small number of families, there
is mutation on chromosome 9. Brain atrophy is
mild and involves anterior parts of the frontal, parietal and temporal lobe. There are microvacuolar changes in outer cortical layers, atrophy in the
lower brain stem and anterior horns of the medulla spinalis. Vacuolization is the consequence of reduction of neurons and not enlargement as in prion diseases.
Dementia usually develops first and then amyotrophy and fasciculations. As in other types of fvFTD,
there are changes in behavior, language, social disinhibition and finally apathy (35,26). Neuropsychological findings are dysexecutive syndrome, attention problems, difficulties in abstract thinking,
working memory, and occurrence of stereotypical
behavior, nonfluent aphasia and echolalia.
Corticobasal degeneration. CBD has onset in
the seventh decade and lasts typically 6 to 7 years.
Characteristic are unilateral akynesia, not dopareactive plastic rigidity, myoclonus limb dystonia,
and more rarely axial dystonia, alien hand sign,
disturbances of cortical sensibility and ideomotor apraxia (36). Asymmetrical cortical findings of
parietal and fronto-temporal atrophy are obvious
both in the clinical picture and on neuroimaging
(37). There is atrophy of the middle third of the
corpus callosum. There are also changes in behavior and language. Dysexecutive symptoms are not
so frequent in CBD as in typical fvFTD but comprise more pronounced visuospatial disturbances

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Pavlovi D. et al.

(38). Most characteristic histological changes are

cortical plaques containing tau protein in astrocytes.

tential drawback of antipychotics in patients with

FTD is reduction of already diminished dopaminergic innervation (42). There are still no studies
on therapy of apathy in FTD with psychostimulants (23).

DIAGNOSIS OF FTD
The diagnosis of FTD is difficult because of variability of the clinical picture and overlap with
many other diseases. Differential diagnosis includes affective disturbances, psychosis, Alzheimers disease, Parkinsons disease and MND (1). Diagnosis of FTD necessitates detailed heteroanamnesis, clinical observation, routine laboratory tests,
structural and functional neuroimaging, neuropsychological assessment and normal electroencephalographic findings. Neuroimaging shows atrophy of the frontal and anterior temporal lobes.
Functional imaging such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT) is used (39).
Core clinical criteria for diagnosis are: insidious
onset and gradual progression, early decline in social relations, early loss of behavioral control, early
occurrence of emotional blunting and early loss of
insight. Supporting features are: decline in personal hygiene and grooming, mental rigidity and inflexibility, distractibility and impersistence, hyperorality and dietary changes, perseverative and stereotyped behavior and utilization behavior (40).
There are suggestions for changes of the current
criteria. They should include specific neuropsychological characteristics, neuroimaging criteria,
activities of daily living and additional clinical criteria of hyperorality, mental rigidity, distractibility
and stereotypic behavior (41).
THERAPY OF FTD
In the absence of causal therapy, symptomatic therapy of FTD is applied to correct behavioral
changes, with the use of antidepressants and nonpharmacological measures (3,26). Serotonin deficit is present in FTD but serotonergic therapy does
not lead to substantial clinical improvements (42).
Pilot studies with cholinesterase inhibitors showed
some positive effects (43). Sometimes atypical antipsychotics (risperidone, olanzapine, quetiapine
and aripiprazole) and psychostabilizers (carbamazepine, valproate and lamotrigine) (23). A po-

Future therapy targets would be tau kynases such

as glycogen synthase kinase 3-and cyclin-dependant kinase 5 (counteracts the tau hyperphosphorilation), heat shock proteins and ubiquitin proteasome system (protective ubiqitination of tau),
inhibition of fibrillization, microtubule stabilizers
and neuroprotective substances (4). Increasing the
level of progranuline by the way of micro deoxyribonucleic acid is a potential therapy in patients
with this type of mutation (44).
Nonpharmacological measures are also important in patients with FTD. They encompass family member education about the disease characteristics, teaching them behavioral interventions, environmental modification, adequate nutrition and
physical activity (23).

REFERENCES
1. Sjgren M, Andersen C. Frontotemporal dementia--a brief review. Mech Ageing Dev
2006;127:180-7.
2. Jellinger KA. What is new in degenerative dementia disorders? Wien Klin Wochenschr
1999;111:682-704.
3. Pavlovi DM. Demencije klinika dijagnostika, II izdanje. Beograd: Kaligraf, 2008.
4. Trojanowski JQ, Duff K, Fillit H, Koroshetz
W, Kuret J, Murphy D, et al. New directions
for frontotemporal dementia drug discovery.
Alzheimers Dement 2008;4(2):89-93.
5. Pasquier F, Petit H. Frontotemporal dementia:
Its rediscovery. Eur Neurol 1997;38:1-6.
6. Mariani C, Defendi S, Mailland E, Pomati S.
Frontotemporal dementia. Neurol Sci. 2006;27
Suppl 1:S35-6.
7. Forman MS, Farmer J, Johnson JK, Clark CM,
Arnold SE, Coslett HB et al. Frontotemporal
dementia: clinicopathological correlations.
Ann Neurol 2006;59:952-62
8. Geser F, Martinez-Lage M, Kwong LK, Lee
VM, Trojanowski JQ. Amyotrophic lateral sclerosis, frontotemporal dementia and

Curr Top Neurol Psychiatr Relat Discip. Vol 19, No. 1, March 2011

17

Pavlovi D. et al.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

18

beyond: the TDP-43 diseases. J Neurol

2009;256(8):1205-14.
Hutton M, Lendon CL, Rizzu P, Baker M,
Froelich S, Houlden H et al. Association of
missense and 5-splice-site mutations in tau
with the inherited dementia FTDP-17. Nature
1998;393:702-5.
Baker M, Mackenzie IR, Pickering-Brown
SM, Gass J, Rademakers R, Lindholm C et al.
Mutations in progranulin cause tau-negative
frontotemporal dementia linked to chromosome 17. Nature 2006;442:916-9.
Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D et al. Null mutations in progranulin cause ubiquitin-positive
frontotemporal dementia linked to chromosome 17q21. Nature 2006;442:920-4.
Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
Scienc 2006;314:1303.
Gass J, Cannon A, Mackenzie IR, Boeve B,
Baker M, Adamson J, et al. Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum
Mol Genet 2006;15:29883001
Zhang YJ, Xu YF, Dickey CA, Buratti E, Baralle F, Bailey R et al. Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J Neurosci 2007;27:10530-4.
Neumann M, Rademakers R, Roeber S, Baker M, Kretzschmar HA Mackenzie IR. A new
subtype of frontotemporal lobar degeneration
with FUS pathology. Brain 2009;132:292231.
Bigio EH, Mishra M, Hatanpaa KJ, White CL
3rd, Johnson N, Rademaker A et al. TDP43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease. Acta Neuropathol
2010;120(1):43-54.
Agosta F, Vossel KA, Miller BL, Migliaccio R,
Bonasera SJ, Filippi M et al. Apolipoprotein E
epsilon4 is associated with disease-specific effects on brain atrophy in Alzheimers disease
and frontotemporal dementia. Proc Natl Acad
Sci U S A 2009;106(6):2018-22.
Brun A, Liu X, Erikson C Synapse loss and
gliosis in the molecular layer of the cerebral
cortex in Alzheimers disease and in fron-

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

tal lobe degeneration. Neurodegeneration

1995;4(2):1717.
Seeley WW. Anterior insula degeneration in
frontotemporal dementia. Brain Struct Funct
2010;214(5-6):465-75.
Young K, Du AT, Kramer J, Rosen H, Miller B, Weiner M, Schuff N. Patterns of structural complexity in Alzheimers disease and
frontotemporal dementia. Hum Brain Mapp
2009;30(5):1667-77.
Grossman M, Libon DJ, Forman MS, Massimo L, Wood E, Moore P et al. Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia. Arch
Neurol 2007;64(11):1601-9.
Hu WT, Mandrekar JN, Parisi JE, Knopman
DS, Boeve BF, Petersen RC et al. Clinical features of pathologic subtypes of behavioral-variant frontotemporal dementia. Arch Neurol 2007;64(11):1611-6.
Mendez MF, Lauterbach EC, Sampson SM;
ANPA Committee on Research. An evidencebased review of the psychopathology of frontotemporal dementia: a report of the ANPA
Committee on Research. J Neuropsychiatry
Clin Neurosci 2008;20(2):130-49.
Rademakers R, Baker M, Gass J, Adamson J,
Huey ED, Momeni P et al. Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C->T (Arg493X) mutation: an international initiative. Lancet Neurol 2007;6:857-68.
Blass DM, Rabins PV. Depression in frontotemporal
dementia.
Psychosomatics
2009;50(3):239-47.
Pavlovi DM. Demencije neuroloki i
psiholoki vodi. II izdanje. Beograd: Kaligraf,
2009.
Lopez OL, Gonzalez MP, Becker JT, Reynolds
CF 3rd, Sudilovsky A, DeKosky ST. Symptoms
of depression in Alzheimers disease, frontal
lobe-type dementia, and subcortical dementia. Ann N Y Acad Sci 1995;769:38992.
Kipps CM, Nestor PJ, Acosta-Cabronero J, Arnold R, Hodges JR.Understanding social dysfunction in the behavioural variant of frontotemporal dementia: the role of emotion and
sarcasm processing. Brain 2009;132(Pt 3):592603.

Curr Top Neurol Psychiatr Relat Discip. Vol 19, No. 1, March 2011

Pavlovi D. et al.

29. Mesulam MM. Slowly progressive aphasia

without generalized dementia. Ann Neurol
1982;11:592-8.
30. Senaha ML, Caramelli P, Porto CS, Nitrini R.
Semantic dementia. Brazilian study of nineteen cases. Dementia & Neuropsychologia
2007;1(4):366-73.
31. Hodges JR, Patterson K, Oxburry S, Funnell E. Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy. Brain
1992;115:1783-806.
32. Joubert S, Felician O, Barbeau E, Sontheimer
A, Barton JJ, Ceccaldi M, Poncet M. Impaired
configurational processing in a case of progressive prosopagnosia associated with predominant right temporal lobe atrophy. Brain
2003;126(Pt 11):2537-50.
33. Foster NL, Wilhelmsen K, Sima AAF, Jones
MZ, DAmato C, Gilman S et al. Frontotemporal Dementia and Parkinsonism Linked to
Chromosome 17: A Consensus Conference.
Ann Neurol 1997;41:706-15.
34. Mann DM. Dementia of frontal type and dementias with subcortical gliosis. Brain Pathology 1998;8:325-38.
35. Avants B, Khan A, McCluskey L, Elman L,
Grossman M. Longitudinal cortical atrophy in amyotrophic lateral sclerosis with
frontotemporal dementia. Arch Neurol
2009;66(1):138-9.
36. Mahapatra RK, Edwards MJ, Schott JM, Bhatia KP. Corticobasal degeneration. Lancet
Neurol 2004;3(12):736-43.
37. Kertesz A, Martinez-Lage P, Davidson W,
Munoz DG. The corticobasal degenera-

38.

39.

40.

41.

42.

43.

44.

Curr Top Neurol Psychiatr Relat Discip. Vol 19, No. 1, March 2011

tion syndrome overlaps progressive aphasia and frontotemporal dementia. Neurology

2000;55:1368-75.
Huey ED, Goveia EN, Paviol S, Pardini M, Krueger F, Zamboni G et al. Executive dysfunction in frontotemporal dementia and corticobasal syndrome. Neurology
2009;72(5):453-9.
Shimizu S, Zhang Y, Laxamana J, Miller BL,
Kramer JH, Weiner MW, Schuff N. Concordance and discordance between brain perfusion and atrophy in frontotemporal dementia.
Brain Imaging Behav 2010;4(1):46-54.
Neary D, Snowden JS, Gustafson L, Passant
U, Stuss D, Black S et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:154654.
Piguet O, Hornberger M, Shelley BP, Kipps
CM, Hodges JR. Sensitivity of current criteria for the diagnosis of behavioral variant frontotemporal dementia. Neurology
2009;72(8):732-7.
Woolley JD, Wilson MR, Hung E, GornoTempini ML, Miller BL, Shim J. Frontotemporal dementia and mania. Am J Psychiatry
2007;164(12):1811-6.
Bei Hu, Ross L, Neuhaus J, Knopman D, Kramer J, Boeve B, et al. Off-label medication use in
frontotemporal dementia. Am J Alzheimers
Dis Other Demen 2010;25(2):128-33.
Jiao J, Herl LD, Farese RV, Gao FB. MicroRNA-29b regulates the expression level of human progranulin, a secreted glycoprotein implicated in frontotemporal dementia. PLoS
One 2010 May 10;5(5):e10551.

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