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behavioural syndrome.7The term—which superseded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
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