Frontotemporal dementia (FTD) is the most common
of a group of clinical syndromes associated with
circumscribed degeneration of the prefrontal and
anterior temporal lobes (figure 1) and non-Alzheimer
disease type pathology, which has been called
frontotemporal lobar degeneration (FTLD). Behavioural
changes are the presenting feature and dominate the
clinical picture throughout the disease course.1–6
Qualitative changes in language and cognitive
impairments in executive function also occur. The
absence of early neurological signs and findings of
focal abnormalities in the frontotemporal lobes on
neuroimaging, contribute to the clinical diagnosis
Terminology and clinical criteria
Use of the term FTD is not consistent. The term was
introduced by workers in Lund (Sweden) and
Manchester (UK) to refer specifically to the progressive
behavioural syndrome.7The term—which superseded
labels such as frontal-lobe dementia and dementia of
frontal type—drew attention to the fact that the
behavioural disorder is invariably associated with
atrophy of both frontal and anterior temporal lobes.
Some patients also develop motor-neuron disease
(MND),8,9a syndrome designated FTD-MND.9
Clinical and pathological diagnostic criteria for FTD,
developed by the Lund and Manchester groups,7showed
good discrimination between FTD and Alzheimer’s
disease.10However, no guide was given as to the number
of clinical features necessary for diagnosis or the relative
importance of symptoms, and no precise operational
definitions of symptoms. Moreover, other clinical
syndromes are also associated with FTLD, determined
only by the distribution of the pathological process
within the frontal and temporal lobes of the brain,
namely progressive aphasia4,11
Non-fluent progressive aphasia is a
disorder predominantly of expressive language, in which
severe problems in word retrieval occur in the context of
preserved word comprehension. This disorder is
associated with asymmetric atrophy of the left
hemisphere. Semantic dementia is a multimodal
disorder of meaning, in which patients lose the abilities
to name and understand words and to recognise the
significance of faces, objects, and other sensory stimuli.
This disorder is associated with bilateral, commonly
asymmetric, atrophy of the middle and inferior temporal
neocortex. Predictably, some patients have a mixed
clinical picture of FTD, progressive aphasia, and
semantic dementia,14and these different syndromes may
be seen within the same family.15,16Because FTLD can be
associated with degeneration of bulbar neurons and
anterior horn cells of the spinal cord, the fact that MND,
most commonly associated with FTD (FTD-MND), has
also been described in the syndromes of semantic
dementia and progressive aphasia, is not surprising.17–19
Clinical criteria published in 1998 (panel) recognised
FTD as one of three major clinical syndromes of FTLD,6
Lancet Neurol2005; 4: 771–80
Clinical Neuroscience Group,
Hope Hospital, Salford, Greater
Manchester M6 8HD, UK
http://neurology.thelancet.com Vol 4 November 2005771
Frontotemporal dementia (FTD) is a focal clinical syndrome characterised by profound changes in personality and
social conduct and associated with circumscribed degeneration of the prefrontal and anterior temporal cortex. Onset
is typically in the middle years of life and survival is about 8 years. The presence of microtubule-associated-protein-
tau-based pathological features in some patients and the discovery, in some familial cases, of mutations in the tau
gene links FTD to other forms of tauopathy, such as progressive supranuclear palsy and corticobasal degeneration.
However, more than half of all patients with FTD, including some with a strong family history, show no apparent
abnormality in the tau gene or protein, indicating pathological and aetiological heterogeneity. FTD provides a
challenge both for clinical management and for theoretical understanding of its neurobiological substrate.
David Neary, Julie Snowden, David Mann
Figure 1:Brain of a patient with frontotemporal dementia showing atrophy
of the frontal and anterior temporal lobes
Sex distribution (men:women)
Age of onset (years)
Duration of illness (years)
45–65 (range 21–85)
6–8 (3 in FTD-MND)
Common; present in 40–50%
Executive deficits; changes in speech and language
Commonly absent early; parkinsonism late; MND in small proportion
Abnormalities in frontotemporal lobes, especially on functional imaging
FTD=frontotemporal dementia; MND=motor neuron disease.
Table:Clinical diagnostic features of frontotemporal dementia
the other prototypical syndromes being non-fluent
progressive aphasia and semantic dementia. A study of
the criteria, based on 34 patients with pathologically
diagnosed FTLD among a series of 433 individuals,
reported good premortem diagnostic accuracy, with a
sensitivity of 85% and specificity of 99%.20
McKhann and colleagues21suggested that, although
these criteria are useful for research, simpler guidelines
are needed for general physicians to facilitate
recognition of FTD and expedite referral to a specialist
centre. Their simplified criteria subsume progressive
aphasia and semantic dementia under the rubric of FTD
and consist of the following six features: (1) early and
progressive change in personality or language;
(2) impairment in social and occupational functioning;
(3) a gradual and progressive course; (4) exclusion of
other causes; (5) presence of deficits in the absence of
delirium; and (6) exclusion of psychiatric causes such as
The usefulness of these latter criteria for the general
physician has yet to be assessed. The criteria are
sufficiently broad that they are likely to have high
sensitivity, yet inevitably at the expense of diagnostic
specificity. The criteria would, for example, incorrectly
include patients with Alzheimer’s disease who present
with language rather than memory impairment.
Moreover, the heuristic value of submerging highly
distinct clinical syndromes under the single diagnostic
label of FTD is open to question.
Some investigators have adopted the terms frontal-
variant FTD for the behavioural syndrome of FTD and
temporal-variant FTD to refer to the clinical syndrome of
semantic dementia.22,23Use of these terms draws
attention to the link between the two syndromes, and the
fact that the syndromes merely indicate differences in
the distribution of pathological changes.4,24A potential
source of confusion is that there is not an exclusive
relation or one-to-one correspondence between the
syndrome and atrophy. Patients with semantic dementia
always have temporal-lobe atrophy, but the presence of
temporal-lobe atrophy does not inevitably denote the
clinical syndrome of semantic dementia. Patients with
the behavioural disorder of FTD invariably have both
frontal-lobe and temporal-lobe atrophy, and in some
cases the temporal-lobe atrophy is greater, even in the
absence of obvious semantic impairment.4Predominant
frontal or temporal atrophy, as determined by MRI of
the brain, cannot therefore be used as a reliable predictor
of the clinical syndrome, which can only be determined
by neuropsychological examination. As a consequence,
reports of temporal variant FTD denote different groups
of patients depending on whether they are defined on
neuropsychological or neuroimaging grounds.22,25,26
In this review, we use the term FTD in its originally
defined sense to refer to the behavioural syndrome
associated with degeneration of the frontal and temporal
lobes (figure 2). However, comparison of results from
independent studies of FTD is potentially confounded by
differences in the definition of patients, as described
above. The designation FTLD is used here in preference
to Pick’s disease, because Pick’s type histological
changes (comprising Pick’s bodies and ballooned
neurons) are seen in only a small proportion of cases.
Moreover, Pick’s type features can be distributed outside
the prefrontal and anterior temporal cortices (the sites of
FTLD), for example, in the parietal lobes and premotor
cortices leading to apraxia,27as seen in progressive
apraxia and corticobasal degeneration.
FTLD comprises atrophy of the prefrontal and anterior
temporal neocortex. Differences in topographical
distribution of atrophy determine the clinical syndromes
http://neurology.thelancet.com Vol 4 November 2005
Panel:Consensus guidelines for the clinical diagnosis of frontotemporal dementia
Clinical profile: character change and disordered social conduct are the dominant
features initially and throughout the disease course.
Core diagnostic features
Insidious onset and gradual progression
Early decline in social interpersonal conduct
Early impairment in regulation of personal conduct
Early emotional blunting
Early loss of insight
Supportive diagnostic features
Decline in personal hygiene and grooming
Mental rigidity and inflexibility
Distractibility and impersistence
Hyperorality and dietary changes
Perseverative and stereotyped behaviour
Speech and language
Altered speech output: aspontaneity and economy of speech; press of speech
Stereotypy of speech
Akinesia, rigidity and tremor
Low and labile blood pressure
Neuropsychology: significant impairment on frontal lobe tests in the absence of severe
amnesia, aphasia, or perceptuospatial disorder
Electroencephalography: normal on conventional electroencephalogram despite
clinically evident dementia
Brain imaging (structural or functional): predominant frontal or anterior temporal
Reproduced with permission from Lippincott, Williams and Wilkins.6
of FTD, semantic dementia, and progressive aphasia
(figure 2). Routine histology shows microvacuolation of
the outer cortical laminae (microvacuolar-type features),
due to large neuronal cell loss, or less commonly,
Immunohistochemical analysis defines four major
types of pathological features (figure 3). (1) Micro-
vacuolation without neuronal inclusions, that is,
dementia lacking distinctive histological features.
(2) Microvacuolation with ubiquitinated rounded
intraneuronal inclusions and dystrophic neurites within
layer 2 of frontal and temporal neocortex and
hippocampal dentate gyrus cells. This is designated
FTLD-ubiquitinated (FTLD-U) type. (3) Transcortical
gliosis with tau-reactive rounded intraneuronal inclusions
(Pick’s bodies) and (usually) swollen achromatic neurons
(Pick’s cells). These histological features are referred to as
being of Pick’s type.7(4) Microvacuolation and tau-
positive neurofibrillary tangles or Pick-like bodies in
neurons, and sometimes tangles in glial cells of the
cerebral cortical white matter. This is associated with
familial FTD because of mutations in the tau gene. Types
3 and 4 are referred to as tauopathies.
Clinical and histological correlations
In individual cases of FTD, progressive aphasia, or
semantic dementia the underlying histological changes
cannot be precisely inferred on the basis of the clinical
syndrome. Each histological type can be associated with
each clinical syndrome (figure 2).4,24,28
pathological studies of FTLD, without clinical data, there
are substantial differences in the reported proportion of
cases showing each histological type, particularly if
degeneration are included as FTLD. Moreover, there
palsy and corticobasal
http://neurology.thelancet.com Vol 4 November 2005773
Pick’s bodies Neurofibrillary
Microvacuolation of upper
Gliosis of cortex and
subcortical white matter
DLDH FTLD-U Tauopathy
Figure 2:Relation between the different levels of description of
frontotemporal lobar degeneration (FTLD)
DLDH=dementia lacking distinctive histological features; FTD=frontotemporal
dementia; FTLD-U=frontotemporal lobar degeneration, ubiquitinated type.
Figure 3:Histological changes in the cerebral cortex
Microvacuolation (dementia lacking distinctive histological features) in upper layers of the cerebral cortex (A).
Ubiquitin inclusions in the cerebral cortex (B). Pick’s bodies in patient with frontotemporal dementia and
parkinsonism associated with chromosome 17 (FTDP-17; Q336R mutation; C). Neurofibrillary tangles in patient
with FTDP-17 (+16 exon 10 splice mutation; D).
may be variations in clinical designation. Nevertheless,
some broad generalisations can be drawn from the
published research and our own data based on
68 necropsied patients.24,28–33In cases that fulfil the strict
clinical criteria for FTD,6the most common histological
feature is tauopathy. In clinical cases of FTD-MND the
histological features are typically non-tau, about 50% of
patients have FTLD-U changes in the cerebral cortex and
brainstem. Initially this was termed as being of MND
type.7However, FTLD-U features are present in many
patients without clinical evidence of MND during life.
Moreover, half of cases of clinical FTD-MND have no
distinct histological features. Accordingly, the term
FTLD-U should be reserved for the histological
description and FTD-MND to denote the clinical
disorder. Patients with semantic dementia and
progressive aphasia show a preponderance of non-tau
Prevalence studies of FTD are currently limited. One
study, based on 17 patients with clinically diagnosed
FTD in the Cambridge area of the UK, reported a
prevalence of 15 cases per 100 000 in people age
A study from the Netherlands of
245 patients with FTD in the Zuid-Holland province (the
Netherlands), reported much lower prevalence: 3·6 per
100 000 at age 50–59 years, rising to 9·4 per 100 000 at
age 60–69 years, and falling to 3·8 per 100 000 at age
70–79 years.35The high prevalence arising from the
Cambridge study led the authors to suggest that FTD
may be as common as Alzheimer’s disease before the
age of 60 years. However, clinical data from other
centres do not support this view. In Lund (Sweden),
36 (9%) of 400 consecutive dementia patients with
postmortem confirmation had FTD and 168 (42%) had
Japanese investigators have
reported a ratio about one case of FTD to four of
Alzheimer’s disease.36In Manchester (UK) in patients
with dementia onset before age 65 years, 147 had FTD
compared to 498 with Alzheimer’s disease (ratio about
one to three). The ratio fell to one to 1·7 in patients with
dementia onset before 50 years (69 Alzheimer’s disease
vs 40 FTD). Differences in cohort and population size
and in the criteria used for patient definition are likely to
contribute to differences in findings across centres.
A high familial incidence in FTD is common
(table).1,4,35Familial incidence is likely to be influenced by
geography. FTD families with ?16 exon 10 splice
mutation of tau, from the UK, USA, and Australia, have
been traced to a common founder in North Wales.37
A study of 245 patients from the Netherlands indicated
an equal distribution of FTD among men and women
(49% men, 51% women), similar to findings in the
Manchester series of 210 patients (50% men, 50%
women).4,35Age at onset is typically 45–65 years, with a
mean in the 50s.4,34,35However, pathologically confirmed
and clinically presumed FTD has been recorded in
individuals as young as 21 years and as old as
85 years.38,39Age at onset in familial and sporadic cases
does not differ significantly.40
youngest-onset cases have been sporadic.38,41The median
duration of illness from onset to death is 6–8 years with
a range of of 2–20 years.4,42The presence of neurological
abnormalities is associated with shorter survival.43FTD-
MND is associated with a median survival of only
Abnormal behaviour is, by definition, the dominant
feature of FTD (table). Changes in affect and lack of
concern and insight are strong discriminators between
FTD, Alzheimer’s disease, and vascular dementia.44–46
Patients lack appropriate basic emotions, such as
sadness, and social emotions, such as sympathy and
empathy. Other strong discriminators are the presence
of repetitive, stereotyped
mannerisms, repeated use of a phrase or saying,
complex behavioural routines)4,22,44,45,47–51and changes in
eating habits (gluttony, food fads, sweet food
preference).4,22,25,44,45,48,52,53An additional feature, with high
specificity for FTD although low sensitivity, is an altered
response to sensory stimuli. This includes both reduced
pain response,44,45ascribed to a decrease in motivational
and affective components of pain,54and hypersensitivity
to neutral stimuli.44,45Behavioural inventories of FTD
highlight the unique characteristics of FTD for
Patients with FTD may present as overactive, socially
disinhibited, and fatuous, or conversely as apathetic,
inert, and emotionally blunted.4,45Attention has also been
drawn to a third behavioural phenotype, characterised by
marked stereotypies and associated with muscular
These behavioural variants may indicate
differences in the topographical distribution of patho-
logical features. Functional imaging and post-mortem
pathological examination show involvement predom-
inantly of orbital frontal and anterior temporal cortices in
socially disinhibited patients, but widespread frontal
involvement, extending into dorsolateral frontal cortex in
apathetic patients.4Reports of stereotypic patients have
indicated that atrophy is greatest in the anterior temporal
lobes and striatum.4Patients with FTD with more right-
hemisphere atrophy have greater behavioural change
than those with more left-sided atrophy.25In keeping with
this finding, a correlative study (involving patients with
FTD and those with semantic dementia) found a
correlation between so-called aberrant behaviour and loss
of grey-matter in the dorsomesial frontal lobe that was
greatest on the right.61
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Executive dysfunction characterises FTD, and patients
show impairments in planning, judgment, problem
solving, organisation, attention, abstraction, and mental
flexibility. By contrast, primary instrumental abilities of
language, elementary visual perception, spatial skills,
and memory are well preserved. Spatial skills in
particular are strikingly well preserved, even in advanced
disease. Patients negotiate their environment, localise,
orientate, and align objects with ease, providing a
striking contrast to the spatial impairments typical of
Alzheimer’s disease. Performance is poor on frontal
executive tests3,4,23,62–64and typically well preserved on
visuoconstructional tests65and memory23,63,66,67compared
with that in Alzheimer’s disease.
Test performance in FTD is characterised by failure to
adhere to the rules of the task, impaired generation and
sequencing of information, inattention, impulsivity of
response without checking, concreteness of thought,
impaired set shifting, and response perseveration,4
features that compromise performance not only on
executive tests but also on tasks designed to test other
cognitive domains. Language changes in FTD include
economy of output, concreteness of thought, verbal
stereotypies, echolalia, perseveration, and eventual
mutism (panel). On memory tests, poor attention and
lack of active generation of information impairs
efficiency of recall. On drawing tests, reproductions of
figures may be impaired by poor organisation and
perseverative strokes, whereas spatial configurational
features of performance
Consequently, despite notable differences in behaviour,
neuropsychological test scores may not always reliably
differentiate FTD and Alzheimer’s disease.69–71Reliance
on test scores alone predictably mask qualitative
differences in the reasons for test failure.68,72
Executive test failure in FTD is greatest in patients
with widespread frontal-lobe atrophy extending into
the dorsolateral frontal cortex. By contrast, patients
with relatively restricted orbitomedial frontal-lobe
atrophy may do surprisingly well on traditional frontal-
lobe cognitive tests, despite gross behavioural
change.3,4,73Although executive impairments provide
support for a diagnosis of FTD, their absence does not
are well preserved.68
Emotion processing and social cognition
Two domains that affect social behaviour are emotion
processing and social cognition. Patients with FTD have
impaired recognition of both facial74–78and vocal76
expressions of emotion and have difficulty inferring
what other people feel or think,79–81consistent with a loss
of so-called theory of mind. Such impaired social
cognition occurs in patients with restricted orbitofrontal
atrophy who succeed on traditional tests of frontal-lobe
function, highlighting the importance of this region in
Physical signs and investigations
FTD is commonly associated with an early absence of
neurological signs (table).4However, primitive reflexes
and striatal signs of akinesia and rigidity emerge with
progression of disease. Muscular wasting occurs in the
few patients who develop MND. Myoclonus, cortico-
spinal weakness and ataxia are absent.
On electroencephalogram, an absence of slow waves is
commonly thought of as valuable in differentiating
between FTD and Alzheimer’s disease.3,4,82However, this
differentiating feature has recently been questioned on
the basis of findings of comparable EEG abnormalities
in FTLD and Alzheimer’s disease.83
MRI shows atrophy in the frontal and temporal
lobes,84,85which may be asymmetric.85Abnormalities in
the anterior cerebral hemispheres are also present on
functional imaging with single-photon-emission CT,86
and may be detected even at an early stage of disease by
functional MRI when structural MRI is normal.87PET
studies have indicated the ventromedial frontal cortex as
the critical affected area common to all patients,
supporting the view that this is the earliest site of
In 1998, research showed that familial FTD, linked to a
chromosome-17 locus, was associated with mutations in
tau.89,90Since then, further families and mutations in tau
have been identified (figure 4)—about 35 different
mutations in around 100 families in total. The tau
mutations can be classified according to whether their
primary effect is exerted either at the level of the
translated protein or on alternative RNA splicing of tau
involving exon 10, or both.
Tau, also known as microtubule-associated protein tau
(MAPT), is involved in the regulation of microtubule
assembly and disassembly, and the transport of proteins
and organelles. In healthy adults, six isoforms of tau are
produced. Three isoforms have three microtubule-
binding regions (known as 3R tau), and the others have
four repeats (known as 4R tau). If one or more of the
various isoforms fails to function, or if there is an
http://neurology.thelancet.com Vol 4 November 2005775
Encodes microtubule binding domain
9 1011 1213
Figure 4:taumutations in frontotemporal dementia
Reproduced courtesy of Dr S Pickering-Brown
imbalance in the different variants, microtubule
formation becomes more difficult and the stability of
microtubules formed becomes compromised. Excess or
unused tau can accumulate into indigestible residues
and inclusions, which choke the cell, leading to neuron
dysfunction and death.
Many of the tau mutations exist as missense
mutations within coding regions of exon 1 (R5H, R5L),
exon 9 (K257T, I260V, L266V, G272V), exon 11 (L315R,
S320F, K317M), exon 12 (Q336R, V337M, E342V, K369I)
and exon 13 (G389R, R406W).89–101These genetic changes
affect all tau isoforms, generating mutated proteins that
fail to promote microtubule assembly or facilitate axonal
transport.91,92,95,98,101,102Some of the mutations also increase
the propensity of the mutated tau to self-aggregate into
neurofibrillary inclusions or Pick’s bodies composed of a
mix of 3R and 4R tau.94,95,97,98,101,102
Other tau mutations lie close to the splice donor site of
the intron that follows the alternatively spliced exon 10
or in exon 10 itself.14,89–91,103–116These mutations destabilise
this region, leading to an imbalance or deletion of tau
isoforms, thereby compromising microtubule binding
and function. This results in the aggregation of excess
tau formed into neurofibrils composed of 4R tau.89,103,106
Conversely, the ?K280 mutation destroys the function of
a splice-enhancing region and results in the abolition of
all transcripts containing exon 10.106
Linkage to chromosome 9 in several families clinically
sharing an FTD-MND phenotype has been claimed by
some investigators,117but not confirmed by others,118and
linkage to chromosome 3p11–12 has been reported in a
Danish family showing FTD with frontotemporal
atrophy, neuronal loss, and gliosis.119FTD has been
associated with inclusion body myopathy and Paget’s
disease, a dominant disorder mapping to chromosome
9p21.1–12 and caused by mutant valosin-containing
protein.120–122A combination of behavioural and language
disorders has been described, and neuropathological
examination has shown frontotemporal lobar atrophy,
cortical and subcortical gliosis, and intranuclear
inclusion bodies containing valosin-containing peptide
and ubiquitin in the cerebral cortex, but sparing the
hippocampal dentate gyrus.
Autosomal dominant mutations in the presenilin-1
gene (PSEN1) are generally associated with early-onset
familial Alzheimer’s disease. Nevertheless, in many
such cases, frontal-lobe signs are prominent within the
constellation of more typical Alzheimer’s disease
symptoms. Two PSEN1 mutations with prominent
frontal-lobe signs have been recently reported.123,124One
patient had an M146L mutation with both Pick’s bodies
and typical Alzheimer’s disease plaques,124and another
had a G183V mutation and Pick’s bodies alone.123
Neither case showed neurofibrillary tangles typical of
Several polymorphisms in tau are in complete linkage
disequilibrium and form extended haplotypes, H1 and
H2.125H1 has been widely associated with progressive
supranuclear palsy and corticobasal degeneration.125,126
Tau haplotypes, and perhaps specifically the tau H1H1
genotype, may promote tau dysfunction leading either
towards the 4R tau neurofibrillary tangles of progressive
supranuclear palsy and corticobasal degeneration, or
towards that in FTD with Pick’s type features, in which
the Pick’s bodies are composed typically of 3R tau, but
also of 4R tau in some cases.
Although the apolipoprotein E (APOE) ?4 allele is a
well established risk factor for late-onset sporadic and
familial Alzheimer’s disease, the presence of this allele
does not seem generally to increase the risk of
developing FTLD.127,128However, there is evidence that
the ?4 allele may selectively increase the risk of FTLD in
men.129Many patients with this allele have (sometimes
prominent) deposition of amyloid ? plaques when
disease onset is after age 65 years, or duration of illness
is long and stretches into later life.130
The clinical phenotype in familial cases of FTD is
generally similar to that in sporadic cases.14,131Patients
with tau mutations, both those with missense mutations
leading to Pick’s type histological changes, and those
with mutations affecting exon 10 splicing leading to
tangle-type changes, have been noted to display the
behavioural change of FTD combined with the
comprehension and naming loss of semantic dementia.
Differences in clinical phenotype, with neurological
presentations resembling progressive supranuclear
palsy or corticobasal degeneration
reported.104,111,115However, it is not clear to what extent
specialist bias gives rise to apparent phenotypic
differences, or whether genuine differences represent
the effects of genetic modifiers.132
Despite the varying histological features associated
with FTD, it is likely that all feed a shared
neurodegenerative cascade. Tau mutations devastate the
neurons’ ability to organise microtubule assembly and
disassembly, and therefore crucially disrupt axonal
transport. Genes and proteins involved in producing
FTLD-U features or dementia lacking distinctive
histological features might likewise adversely affect this
fundamental cytoskeletal function, converging on the
same physiological problem, and thereby generating a
similar clinical disorder.
Pharmacological treatments for FTD are limited. Data
from neurochemical studies of necropsied brains133,134
and functional imaging using PET135,136have indicated
abnormalities in serotonin metabolism, which have led
to clinical trials of drugs with serotoninergic effects. The
results of trials of modulation of serotonin in FTD using
http://neurology.thelancet.com Vol 4 November 2005
selective serotonin reuptake inhibitors have been
equivocal.137–141Interestingly, concentrations of serotonin
and its metabolites are high in some cases of FTLD.142A
reduction in serotonin receptors on glutamatergic
cortical pyramidal neurons may simply indicate
neuronal cell loss. However, the preservation of
serotonin afferents, which are inhibitory, could lead to
an excess of extraneural serotonin, causing underactivity
of a depleted pool of surviving glutamatergic pyramidal
neurons. Accordingly, trials of treatment with serotonin
antagonists may be indicated.
Management of patients with FTD concentrates
mainly on the construction of a support network
through social, psychiatric, and voluntary services,
enabling provision of such facilities as day, respite, and
ultimately residential care, to relieve the immense
burden on families. Services are often best provided by
psychiatry services for elderly people, regardless of
patients’ ages, although access to those services may be
limited for people with early-onset dementia and
Growth in interest in FTD in recent years indicates the
rapid advances in the understanding of its pathological
and molecular basis. Better understanding has, however,
revealed increased complexity. FTD is associated with
distinct histological features, different immunochemical
characteristics, and different genetic bases. FTD
presents a challenge for management. There is a need
for better symptomatic treatment and better resources
for care of these patients and their families.
JS and DM did the literature search. DM provided the pathological
figures. All authors contributed to the selection of references and the
writing of the review.
Conflicts of interest
There are no conflicts of interest.
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Search strategy and selection criteria
References for this review were identified in March, 2005, by
searches of the PubMed database between 1995 and 2005
using the term “frontotemporal dementia”. Articles were also
identified from the authors’ personal files. Only papers
published in English were reviewed. Articles were selected on
the basis of their originality and relevance.
29 Bergmann M, Kuchelmeister K, Scmid KW, et al. Different
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44 Bathgate D, Snowden JS, Varma A, Blackshaw A, Neary D.
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50 Mendez MF, Perryman KM, Miller BL, et al. Compulsive
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54 Scherder EJ, Sergent JA, Swaab DF. Pain processing in dementia
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55 Barber RA, Snowden JS, Craufurd D. Retrospective differentiation
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67 Lee AC, Rahman S, Hodges JR, Sahakian BJ, Graham KS.
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73 Gregory CA, Serra-Mestres J, Hodges JR. Early diagnosis of the
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74 Lavenu I, Pasquier F, Lebert F, Petit H, van der Linden M.
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75 Lavenu I, Pasquier F. Perception of emotion on faces in
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76 Keane J, Calder AJ, Hodges JR, Young AW. Face and emotion
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77 Rosen HJ, Perry RJ, Murphy J, et al. Emotion comprehension in
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79 Lough S, Gregory C, Hodges JR. Dissociation of social cognition
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80 Gregory C, Lough S, Stone V, et al. Theory of mind in patients
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85 Whitwell JL, Anderson VM, Scahill RI, Rossor MN, Fox NC.
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87 Rombouts SA, van Swieten JC, Pijnenburg YA, Goekoop R,
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