Proposed diagnostic criteria for apathy in Alzheimer’s disease and other
P. Roberta,*, C.U. Onyikeb, A.F.G. Leentjensc, K. Dujardind, P. Aaltenc, S. Starksteine,
F.R.J. Verheyc, J. Yessavagef,g, J.P. Clementh, D. Drapieri, F. Baylej, M. Benoitk, P. Boyerl,
P.M. Lorcam, F. Thibautn, S. Gauthiero, G. Grossbergp, B. Vellasq, J. Byrner
aCentre Me ´moire de Ressources et de Recherche, CHU de Nice, Nice, France
bDivision of Geriatric Psychiatry and Neuropsychiatry, The Johns Hopkins School of Medicine, Baltimore, MD, USA
cDepartment of Psychiatry, Maastricht University Medical Center, Alzheimer Center Limburg, Maastricht, The Netherlands
dNeurology and Movement Disorders Unit, EA2683, Faculty of Medicine and Lille University Hospital, Lille, France
eDepartment of Psychiatry, University of Western Australia, Australia
fSierra-Pacific Mental Illness Research, Education, and Clinical Center, Palo Alto VA Health Care System, USA
gDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, USA
hJ.P. Clement CMRR du Limousin, CHU-CH, Limoges, France
iDepartment of Psychiatry, Unite ´ de Recherche Universitaire «Comportements et noyaux gris centraux» Universite ´ de Rennes, France
jUniversite ´ Paris Descartes, CH Sainte-Anne, INSERM U 796, Paris, France
kCentre Me ´moire de Ressources et de Recherche, Department of Psychiatry CHU de Nice, France
lInstitute of Mental Health Research, Ottawa, Ontario, Canada
mUniversite ´ d’Auvergne, CHU Clermont-Ferrand, France
nUniversity Hospital Ch Nicolle, INSERM U 614, University of Medicine, Rouen, France
oMcGill Center for Studies in Aging, Douglas Mental Health Research Institute, Canada
pDepartment of Neurology and Psychiatry, St Louis University School of Medicine, St Louis, MO, USA
qGerontopole, Inserm U 558, CHU Toulouse, France
rOld Age Psychiatry, University of Manchester, UK
Received 2 June 2008; received in revised form 3 September 2008; accepted 7 September 2008
Available online 7 February 2009
There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer’s disease and in various neuropsychiatric
disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to
develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research
settings. Meeting these needs is the focus of the task force work reported here.
The task force includes members of the Association Franc ¸aise de Psychiatrie Biologique, the European Psychiatric Association, the European
Alzheimer’s Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting
(during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria.
Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of
apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed
behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments
attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.
? 2008 Published by Elsevier Masson SAS.
Keywords: Apathy; Alzheimer’s disease; Neuropsychiatry; Diagnostic criteria
* Corresponding author. Centre Me ´moire de Ressources et de Recherche, Pavillon Mossa, Ho ˆpital de Cimiez, 4 Avenue Reine Victoria, 06003 NICE Cedex 1,
France. Tel.: þ33 4 92 03 47 70; fax: þ33 4 92 03 47 72.
E-mail address: firstname.lastname@example.org (P. Robert).
0924-9338/$ - see front matter ? 2008 Published by Elsevier Masson SAS.
Available online at
European Psychiatry 24 (2009) 98e104
The word apathy, stemming from the Greek original apa-
theia (derived from apathes e ‘a’ (without) þ ‘pathos’
(feeling)) has undergone changes in meaning over the ages,
and the modern construct presents apathy as a state of indif-
ference or inertia, and as a disability or a maladaptive state.
The semantic confusion related to shifts in meaning is one of
the problems that have confounded the study of apathy in
neuropsychiatry. Even today, confusion remains regarding the
essential features of apathy and its boundaries with constructs
such as aboulia, anhedonia, depression and learned helpless-
ness. Consider, for example, that the Oxford English Dictio-
nary defines apathy as a lack of interest or enthusiasm, an
approach emphasizing a ‘cognitive’ dimension (interest) and
a ‘feeling’ or ‘emotional’ dimension (enthusiasm). The same
source defines aboulia (from the Greek ‘a’ (without) þ ‘boule’
(will)) as a related concept that denotes absence of the will or
power to generate focused action. In psychiatry, aboulia is
considered by some to be a severe form of apathy . Indeed,
psychiatrists and neurologists responding to a survey consid-
ered aboulia to be a state characterized by difficulty in initi-
ating and sustaining spontaneous movements, and reductions
in emotional responsiveness, spontaneous speech, and social
interaction , but also acknowledged that its status as
a syndrome was controversial. The conceptualization of
apathy noted in that study overlaps with the notion of apathy
as a disorder of interest and enthusiasm, while also adding
a ‘motor’ dimension (initiation and maintenance of move-
ment) and a ‘behavioural’ dimension (social interaction).
Modern conceptualizations of apathy reflect efforts to
reconcile the various dimensions of apathy. Despite differ-
ences, such as, for example, disagreements as to whether
disturbances of motivation  or of initiative and self-
generated voluntary and purposeful behaviour [48,26] are
central features, most conceptualizations of apathy acknowl-
edge that it is a syndrome in which all these dimensions are
prominent (see Table 1). Another source of difficulty in the
study of apathy (i.e., besides the semantic disagreements) is
that the dimensions within the construct, such as motivation
and interest, are latent variables so that their ‘quality’ and
‘quantity’ must be inferred by observing patient behaviour
. Fortunately, areas of agreement allow a common point of
departure for the characterization and study of apathy. There is
presently wide agreement that motivation, interest, action
initiation and emotional reactivity are dimensions of apathy,
and that lack of motivation is at the core of the disorder. An
introspective dimension (lack of self-awareness, reflecting
poor self-monitoring and self-management) is still debated.
From this platform, Starkstein and colleagues have developed
a set of diagnostic criteria for apathy , adapted from the
work of Marin ; these criteria specify the following as core
features of apathy: diminished motivation, initiative and
interest, and blunting of emotions.
2. Why new criteria for apathy?
Broadly speaking, two principal reasons exist for formu-
lating formal consensus criteria regarding apathy in dementia
and neuropsychiatry: (1) recognition of its growing impor-
tance to neuropsychiatric research and practice, and (2) the
need for reliable case description and identification, to facili-
tate communication, research and treatment. We review these
There is presently wide acknowledgement that apathy is an
important behavioural syndrome in various neuropsychiatric
disorders. Apathy is common in diseases such as Alzheimer
disease, Parkinson’s disease and associated dementias, fron-
totemporal dementias and stroke [25,49]. It is the most
frequent neuropsychiatric symptom in AD [31,39] and in
many other dementias, and presents at all stages of the disease
(Table 2). In addition, apathy occurs as a stable syndrome in
AD. Apathy in AD, or other dementias, is generally accom-
panied by heightened functional disability and by greater carer
burden and stress [24,34].
Studies of the classification or clustering of neuropsychi-
atric symptoms in dementia, typically using the Neuropsy-
chiatric Inventory (NPI)
consistently identified apathy as ‘‘classes’’ or ‘‘factors’’. For
example, in the EADC (European Alzheimer’s Disease
Consortium) study , principal component analysis of cross-
sectional data from 2354 patients with AD segregated four
syndromes: hyperactivity, psychosis, affective and apathy. The
apathy syndrome was the most common, occurring in almost
65% of the patients. A later analysis of data from the same
sample provided indications of stability of the same
including vascular dementia, dementia with Lewy bodies and
frontotemporal dementia . Thus apathy is prominent among
the neuropsychiatric complications of dementia, and is liable
to co-exist with other disabling phenomena.
Concepts of apathy
Marin et al. Disorder of motivation with cognitive,
sensory, motor and affective subtypes
Disorder of interest or motivation;
including lack of emotion, lack of initiation,
lack of enthusiasm
Disorder of initiative, manifesting lack of
self-initiated action, which may be affective,
behavioural or cognitive and includes
‘‘social apathy’’ e a disorder of sense of
self and of social awareness
Disorder of motivation with emotional
blunting, lack of initiative, lack of interest
Disorder of intellectual curiosity, action
initiation, emotion and self-awareness
Disorder of voluntary and goal-directed
behaviours; with three subtypes of disrupted
‘‘signal’’ processing: e emotional-affective,
cognitive and auto-activation
Disorder of motivation with diminished
goal-directed behaviour and cognition
Cummings et al. 
Stuss et al. 
Robert et al. 
Sockeel et al. 
Levy and Dubois 
Starkstein and Leentjens 
P. Robert et al. / European Psychiatry 24 (2009) 98e104
There is also a growing body of evidence indicating that
apathy is a prominent feature of pre-dementia states
[27,10,37,18,22,34,6]. Indeed, there are indications that apathy
may be predictive of later dementia . One study of patients
with mild cognitive impairment (MCI) found that the risk of
conversion to AD was significantly higher for patients mani-
festing lack of interest, their main indicator of apathy .
Another important reason is the well-established overlap
between apathy and depression. Although both conditions
share common features, they are distinct and separable with
careful measurement in dementia  and milder cognitive
syndromes . Older individuals who have apathy are more
likely than those who have depression (and those who have
neither condition) to have cognitive disorders [23,30]. Thus,
formal criteria for the diagnosis of apathy can be expected to
facilitate the recognition of apathy in elders, in turn increasing
the likelihood of early identification of individuals with
cognitive impairment or mild dementia. Furthermore, when
apathy and depression co-occur, identification of apathy may
be helpful in the interpretation of unsatisfactory treatment
response and in the formulation of alternative treatment
In addition, establishment of consensus criteria may
enhance the quality of clinical care for patients with dementia,
since apathy may be a treatable condition. In a recent review
of the literature on the efficacy of cholinesterase inhibitors in
AD , it was reported that whilst many types of behaviour
may be ameliorated, apathy, delusions and aberrant motor
behaviour are the most likely to improve. Recently, clinical
trials have provided indications that focused pharmacotherapy
may be beneficial for apathy in Parkinson disease  and in
dementia [20,35]. Apathy has also been a target of the non-
pharmacological interventions [6,21,36].
In light of research developments and the renewed interest
in the correlates and impacts of apathy, and in treatments, it is
important to develop criteria for apathy status that will be
widely accepted, have clear operational steps, and that will be
easily applied in practice and research settings. Meeting these
needs is the focus of the work reported in this paper.
Under the auspices of the AFPB (Association Franc ¸aise de
Psychiatrie Biologique) and the EPA (European Psychiatric
Association), a task force was set up to revise the Starkstein
criteria for apathy . This task force was chaired by Phil-
ippe Robert and included members of the AFPB, EPA and the
European Alzheimer’s Disease Consortium (EADC), invited
on the basis of their expertise in the neuropsychiatry of
neurodegenerative diseases. The task force also included other
experts from within Europe, and from Australia and North
A statement of goals and conceptual questions regarding
proposed criteria for apathy in AD and other neurodegenera-
tive diseases was circulated to members of the task force at the
beginning of the process in December 2007. Following this,
a succession of draft proposals were sent out between
December 2007 and April 2008 for review, commentary and
editing. An advanced draft of proposed criteria was reviewed
and discussed at the consensus meeting (during the EPA
conference in Nice, France, in April 7th 2008), during which
outstanding conceptual and semantic issues were discussed
and a final agreement reached concerning operational defini-
tions and hierarchy of the criteria.
4. Revised criteria for apathy
The revised criteria (see Table 3) follow the same general
structure as the criteria proposed by Sergio Starkstein and
colleagues in 2001 ; firstly (A) a general statement on the
Frequency of Neuropsychiatric symptoms evaluated with the NPI in 2 European studies with different cut off scores
NPI DomainICTUS study symptom present if NPI score >3REAL study symptom present if
NPI score >0
Aberrant motor behaviour
NPI¼neuropsychiatric inventory, CDR¼clinical dementia rating, MMSE¼mini mental state examination.
REAL: the multicenter PHRC REAL-FR cohort is a longitudinal study for community-dwelling patients with a diagnosis of AD. NPI was completed at study entry
for 499 patients .
ICTUS e EADC: European Alzheimer Disease Consortium: the ICTUS study is an ongoing longitudinal prospective observational study of patients with Alz-
heimer’s disease recruited in 29 centers in Europe. NPI was completed at study entry for 1345 patients .
P. Robert et al. / European Psychiatry 24 (2009) 98e104
core feature of apathy being diminished motivation; secondly
(B 1e3) a description of the three dimensions of apathy;
thirdly (C) a requirement for functional impairments attributed
to the apathy; and fourthly (D) specific exclusion criteria.
Here, we explain the consensus reached by the task force for
the revision of each section (AeD).
Apathy is a syndrome with three domains (B) the core
feature being a loss or diminution of motivation (A). For
a diagnosis of apathy the patient should fulfil each of the
criteria A, B, C and D.
Criterion A stipulates loss of or diminished motivation,
which may be reported by the patient or by observers who are
familiar with the patient. This criterion defines apathy as
a disorder of motivation. Consensus exists that loss of or
diminution of motivation (relative to a lifelong level of func-
tioning and the standards of the patient’s age and culture) is
central to virtually all modern definitions or conceptualiza-
tions of apathy (see Table 1), and that it should represent the
core criterion for the syndrome of apathy, with its components
(or ‘‘specific symptoms’’) further defined in Criterion B.
Criterion B indicates that apathy is generally a persistent
state, rather than a transient or intermittent one by incorpo-
rating in the definition a minimum duration of four weeks, as
suggested by Starkstein and Leentjens  in recent work.
This criterion was added to differentiate from the transient
states that may mimic the apathy of primary dementias, such
as to occur during ‘off’ periods in Parkinson’s disease patients,
during hypo-arousal in delirium, and during acute emotional
responses to stress.
Criterion B is also based on the premise that change in
motivation can be observed (and measured) by examining
a patient’s responsiveness to internal or external stimuli. Each
of the three domains within Criterion B (behaviour, cognition
and emotion) includes two symptoms. The first symptom
pertains to self-initiated or ‘internal’ actions, cognitions and
emotions, and the second symptom to the patient’s respon-
siveness to ‘external’ stimuli.
Domain B1, stipulates loss of or diminished goal-directed
behaviour, specifically loss of self-initiated behaviour and loss
of environment-stimulated behaviour. These were found to be
the most frequently occurring
a prospective European multi-centre study (ICTUS) that
evaluated 216 AD patients for apathy, using the Apathy
Inventory. This criterion is also based on the understanding
that reductions in goal-directed behaviour affect routine
example ‘communicating choices’ identifies goal-directed
prosocial behaviour, although there is a potential for its
ascertainment to become confounded with executive functions
such as decision-making.
Domain B2, referring to reduced goal-directed cognitive
activity, is usually interpreted in practical terms as a loss of or
diminished interest that is most often observed in leisure
activities . This domain indicates that the patient is less
interested in the activities and plans of others, in friends and
family members, or in their own usual leisure activities or
‘internal’stimuli isdependent on a number offactors relating to
the individual, such as personality, culture and education.
Conceptually, the affective aspects of interest, such as excite-
ment, overlap with domain B3 (i.e., with goal-directed feelings,
see below),thus introducing a potential source ofascertainment
error(i.e.,violationof the unstated assumptionthat domains B2
Apathy proposed criteria
For a diagnosis of Apathy the patient should fulfil the criteria A, B, C and D
A Loss of or diminished motivation in comparison to the patient’s previous level of functioning and which is not consistent with his age or culture. These changes
in motivation may be reported by the patient himself or by the observations of others.
B Presence of at least one symptom in at least two of the three following domains for a period of at least four weeks and present most of the time
Domain B1 : Loss of, or diminished, goal-directed behaviour as evidenced by at least one of the following:
e Loss of self-initiated behaviour (for example: starting conversation, doing basic tasks of day-to-day living, seeking social activities, communicating
e Loss of environment-stimulated behaviour (for example: responding to conversation, participating in social activities)
Domain B2 : Loss of, or diminished, goal-directed cognitive activity as evidenced by at least one of the following:
e Loss of spontaneous ideas and curiosity for routine and new events (i.e., challenging tasks, recent news, social opportunities, personal/family and social
e Loss of environment-stimulated ideas and curiosity for routine and new events (i.e., in the persons residence, neighbourhood or community)
Domain B3 : Loss of, or diminished, emotion as evidenced by at least one of the following:
e Loss of spontaneous emotion, observed or self-reported (for example, subjective feeling of weak or absent emotions, or observation by others of a blunted
e Loss of emotional responsiveness to positive or negative stimuli or events (for example, observer-reports of unchanging affect, or of little emotional
reaction to exciting events, personal loss, serious illness, emotional-laden news)
C These symptoms (AeB) cause clinically significant impairment in personal, social, occupational, or other important areas of functioning.
D The symptoms (AeB) are not exclusively explained or due to physical disabilities (e.g. blindness and loss of hearing), to motor disabilities, to diminished level
of consciousness or to the direct physiological effects of a substance (e.g. drug of abuse, a medication).
P. Robert et al. / European Psychiatry 24 (2009) 98e104
construct, ‘curiosity’, which appears more amenable to oper-
ationalization than interest, was adopted during the consensus
process so as to focus the criterion more securely on the
cognitive aspects of goal-directed behaviour.
Domain B3 focuses on the affective aspects of the lost or
diminished motivation. It also incorporates the construct
‘emotional blunting’, which is widely used to describe the
affective presentation of apathy. However, the challenge was
how exactly to operationalize emotional blunting. The task
force considered that in clinical practice ‘emotional blunting’
can manifest as reduction in a patient’s capacity to express
emotional reactions to everyday events. The task force also
considered the issue of differentiating experienced and
expressed affects, a distinction consistent with the approach
taken in the structuring of domains B1 and B2. Since it is not
clear that loss of ‘experienced’ emotion can be reliably
ascertained or inferred, the approach undertaken was to
substitute ‘observed’ for ‘expressed’ and ‘self-reported’ for
‘‘experienced’’ in laying out the domain B3.
Criterion C refers to functional impairment that is largely
attributable to the symptoms specified in criteria A and B.
Criterion D is intended to exclude from definition condi-
tions and states that mimic apathy, as well as transient states of
apathy that can be attributed to a discrete non-neuropsychiatric
cause. It is widely known that apathy (in neuropsychiatric
disorders) frequently co-exists with other syndromes, espe-
cially depression. The task force emphasizes the importance of
distinguishing apathy from depression in neuropsychiatric
disorders (and from other co-existing syndromes), and notes
that present-day measures of apathy and of depression facili-
tate the differentiation in practice and research e although
none is entirely satisfactory.
5. Discussion and additional considerations
Although most of the members of the task force are involved
inneuropsychiatry orold-age psychiatry, thetask forceisaware
as major depression and schizophrenia.
For instance an important features of schizophrenia are
negative symptoms . They are characterized by the absence
of normal levels of activation, initiative and affect  and
have been put forward to explain the common phenomenology
of negative symptoms and apathy . Frith  proposed that
behavioural signs associated with negative symptoms could be
understood in terms of a core deficit in the generation of willed
action. Brown and Pluck  referred both apathy and negative
a behavioural point of view lack of initiative and interest, core
dimensions of apathy, is close to ‘‘wanting’’ defined in animal
studies as the underlying implicit motivational component of
reward mediated by mesolimbic dopamine circuitry .
profiles of negative symptoms in schizophrenia, melancholic
depression  and apathy in AD or related disorders . In
AD functional brain imaging studies indicated that the most
to be hypoperfusion and hypometabolism of anterior cingulate
and related frontosubcortical structure [4,12,32].
The cingulate is a nexus that integrates the various
components intended to lead to a goal-directed behaviour. It is
the central part of a corticoesubcortical network and one of its
main characteristics is the importance of afferences coming
from different regions including frontal, vegetative and
sensory processing regions. The cingulate cortex has been
implicated in human clinical conditions such as depression,
pain and distress , attention , reward  and is part of
an executive control network, working in tandem with
prefrontalcortex to ensure
In summary these results suggest that apathy is associated
with other neurobehavioural syndromes, which are felt to
involve dysfunction of frontosubcortical circuits.
Therefore the task force has attempted to formulate the
criteria in such a way that they may be applied to disorders
beyond those that constituted the focus of this work.
A second consideration concerns the assessment of apathy
and present-day assessment instruments for practice and
research. One of the main difficulties in the screening and
assessment of apathy is that apathy in neuropsychiatric
disorders is frequently associated with other phenomena.
Instruments for the assessment of apathy in neuropsychiatric
disorders (whether for screening or for estimating severity)
must reliably distinguish apathy from other syndromes,
particularly depression, which co-exist in these disorders.
Ideally, the assessment should be structured, with input from
the patient and the carer, and should also incorporate the
physician’s perspective. Furthermore, there is much validation
work to be done and the task force is in the process of
developing the relevant research, with the goal of producing
estimates of the reliability and validity of present-day instru-
ments (in relation to the diagnostic criteria). These data, when
available, will facilitate the development of robust measures of
severity and change, for treatment and other research. While
we await the development of instruments that incorporate the
criteria specified in this paper, the following instruments are
recommended for practice and research; the Structured Clin-
ical Interview for Apathy (SCIA) which can be used for
ascertainment of apathy in patients with dementia and other
neurodegenerative diseases, the Apathy Evaluation Scale e
AES , the Apathy Scale e AS , the Apathy Inventory
e AI , the Lille Apathy Rating Scale e LARS . The
AES, AS, AI and LARS have the relevant psychometric
properties for measuring the level of apathy.
Although diagnostic criteria for apathy have been proposed
before and have also been used in research practice, they were
proposed by individuals, and hence have no formal status, i.e.,
they are not part of international classification systems or
endorsed by scientific societies. The present consensus criteria
are the first that have been agreed upon within and between
P. Robert et al. / European Psychiatry 24 (2009) 98e104
scientific associations. The proposed criteria were endorsed by
the participating associations, the French Association for
Biological Psychiatry, the European Psychiatric Association,
and the European Alzheimer Disease Consortium.
These present consensus diagnostic criteria for apathy were
built on the work of others, and are proposed as a synthesis of
current concepts, presented in semi-operationalized form, for
practice and research application in the evaluation of various
neuropsychiatric disorders. We suggest that, at least, these
criteria have heuristic value since they attempt to solidify
a somewhat loosely defined concept and thus make it more
accessible and amenable to scientific study.
The AFPB (Association Franc ¸aise de Psychiatrie Biol-
ogique), the EPA (European Psychiatric Association), the
European Alzheimer’s Disease Consortium (EADC).
 Aalten P, Verhey F, Boziki M, Bullock R, Byrne EJ, Camus V, et al.
Neuropsychiatric syndromes in dementia; results from the European
Alzheimer disease consortium. Dement Geriatr Cogn Disord 2007;24:
 Aalten P, Verhey F, Boziki M, Bullock R, Byrne EJ, Camus V, et al.
Consistency of neuropsychiatric syndromes across dementia; results from
the European Alzheimer disease consortium. Dement Geriatr Cogn
 Andreasen NC. The scale for the assessment of negative symptoms
(SANS): conceptual and theoretical foundations. Br J Psychiatry 1989;7:
 Benoit M, Koulibaly PM, Migneco O, Darcourt J, Pringuey DJ,
Robert PH. Brain perfusion in Alzheimer’s disease with and without
apathy: a SPECT study with statistical parametric mapping analysis.
Psychiatr Res Neuroimaging 2002;114(2):103e11.
 Berridge KC, Robinson TE. What is the role of dopamine in reward:
hedonic impact, reward learning, or incentive salience. Brain Res Brain
 Boyle PA, Malloy PF. Treating apathy in Alzheimer’s disease. Dement
Geriatr Cogn Disord 2004;17(1e2):91e9.
 Breiter HC, Aharon I, Kahneman D, Dale A, Shizgal P. Functional
imaging of neural responses to expectancy and experience of monetary
gains and losses. Neuron 2001;30(2):619e39.
 Brown RG, Pluck G. Negative symptoms: the pathology of motivation
and goal-directed behavior. Trends Neurosci 2000;23(9):412e7.
 Cohen JD, Botvinick MM, Carter CS. Anterior cingulate and prefrontal
cortex: who’s in control? Nat Neurosci 2000;3:421e3.
 Copeland MP, Daly E, Hines V, Mastromauro C, Zaitchik D, Gunther J,
et al. Psychiatric symptomatology and prodromal Alzheimer’s disease.
Alzheimer Dis Assoc Disord 2003;17(1):1e8.
 Corbetta M, Miezin FM, Schulman GL, Petersen SE. A PET study of
visuospatial attention. J Neurosci 1993;13:1202e26.
 Craig AH, Cummings JL, Fairbanks L, Itti L, Miller B, Li J, et al.
Cerebral blood flow correlates of apathy in Alzheimer disease. Arch
 Cummings JL, Mega MS, Gray K, Rosemberg-Thompson S, Gornbein T.
The Neuropsychiatric Inventory: Comprehensive assessment of psycho-
pathology in dementia. Neurology 1994;44:2308e14.
 Cummings JL, Mackell J, Kaufer D. Behavioral effects of current Alz-
heimer’s disease treatments: a descriptive review. Alzheimers Dement
 Czanecki K, Kumar N, Josephs KA. Parkinsonism and tardive antecollis
in frontotemporal dementia increased sensitivity to newer antipsychotics?
Eur J Neurol 2008;15(2):199e201.
 Derouesne ´ G. Apathy: a useful but limited concept. Psychol Neuro-
psychiatr Vieil 2004;2(1):19e28.
 Devinsky O, Morrell M, Vogt B. Contributions of anterior cingulate
cortex to behaviour. Brain 1995;118:279e306.
 Feldman H, Scheltens P, Scarpini E, Hermann N, Mesenbrink P,
Mancione L, et al. Behavioral symptoms in mild cognitive impairment.
 Frith CD. The cognitive neuropsychology of schizophrenia. 1 ed. Hove:
L. Erlbaum Associates Publishers; 1992.
 Hermann N, Rothenburg LS, Black S, Ryan M, Liu BA, Busto UE, et al.
Methylphenidate for the treatment of apathy in Alzheimer disease:
prediction of response using dextroamphetamine. J Clin Psycho-
 Holmes C, Wilkinson D, Dean C. The efficacy of donepezil in the
 Hwang TJ, Masterman DL, Ortiz F, Fairbanks LA, Cummings JL. Mild
cognitive impairment is associated with characteristic neuropsychiatric
symptoms. Alzheimer Dis Assoc Disord 2004;18(1):17e21.
 Kuzis G, Sabe L, Tiberti C, Dorrego F, Starkstein SE. Neuro-
psychological correlates of apathy and depression in patients with
dementia. Neurology 1999;52:1403e7.
 Landes AM, Sperry SD, Strauss ME, Geldmacher DS. Apathy in
Alzheimer’s disease. J Am Geriatr Soc 2001;49:1700e7.
 Levy ML, Cummings JL, Fairbanks LA, Masterman D, Miller BL,
Craig AH, et al. Apathy is not depression. J Neuropsychiatry Clin
 Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal
cortex-basal ganglia circuits. Cereb Cortex 2005:1e13 [published on line
 Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S.
Prevalence of neuropsychiatric symptoms in dementia and mild cognitive
impairment: results from the cardiovascular health study. JAMA 2002;
 Marin RS. Differential diagnosis and classification of apathy. Am J
 Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of
the apathy evaluation scale. Psychiatry Res 1991;38:143e62.
 McPherson S, Fairbanks L, Tiken S, Cummings JL, Back-Madruga C.
Apathy and executive function in Alzheimer’s disease. J Int Neuro-
psychol Soc 2002;8(3):373e81.
 Mega MS, Cummings JL, Fiorello T. The spectrum of behavioral
changes in Alzheimer’s disease. Neurology 1996;46:130e5.
 Migneco O, Benoı ˆt M, Koulibaly PM, Dygai I, Bertogliati C, Desvignes P,
et al. Perfusion brain SPECT and statistical parametric mapping analysis
and non demented patients. NeuroImage 2001;13:896e902.
 Mueser KT, McGurk SR. Schizophrenia. Lancet 2004;363(June 19):
 Onyike CU, Sheppard JM, Tschanz JT, Norton MC, Green RC,
Steinberg M, et al. Epidemiology of apathy in older adults: the Cache
County study. Am J Geriatr Psychiatry 2007;15(5):365e75.
 Padala PR, Burke WJ, Bhatia SC, Petty F. Treatment of apathy with
methylphenidate. J Neuropsychiatry Clin Neurosci 2007;19(1):81e3.
 Politis AM, Vozzella S, Mayer LS, Onyike CU, Baker AS, Lyketsos CG.
A randomized, controlled, clinical trial of activity therapy for apathy in
patients with dementia residing in long-term care. Int J Geriatr Psychiatry
 Ready RE, Ott BR, Grace J, Cahn-Weiner DA. Apathy and executive
dysfunction in mild cognitive impairment and Alzheimer disease. Am J
Geriatr Psychiatry 2003;11(2):222e8.
 Robert P, Berr C, Volteau M, Bertogliati C, Benoit M, Sarrazin M, et al.
Apathy in patients with mild cognitive impairment and the risk of
developing dementia of Alzheimer’s disease: a one year follow up study.
Clin Neurol Neurosurg 2006;108:733e6.
symptoms inAlzheimer disease.
P. Robert et al. / European Psychiatry 24 (2009) 98e104
 Robert P, Verhey F, Byrne EJ, Hurt C, De Deyn PP, Nobili F, et al.
Grouping for behavioral and psychological symptoms in dementia:
clinical and biological aspects. Consensus paper of the European Alz-
heimer disease consortium. Eur Psychiatry 2005;20(7):490e6.
 Robert PH, Berr C, Volteau M, Bertogliati C, Benoit M, Guerin O, et al.
Importance of lack of interest in patients with mild cognitive impairment.
Am J Geriatr Psychiatry 2008;16:770e6.
 Robert PH, Clairet S, Benoit M, Koutaich J, Bertogliati C, Tible O, et al.
The apathy inventory: assessment of apathy and awareness in Alzheim-
er’s disease, Parkinson’s disease and mild cognitive impairment. Int J
Geriatr Psychiatry 2002;17:1099e105.
 Sockeel P, Dujardin K, Devos D, Dene `ve C, Deste ´e A, Defebvre L. The
Lille apathy rating scale (LARS), a new instrument for detecting and
quantifying apathy: validation in Parkinson’s Disease. J Neurol Neuro-
surg Psychiatr 2006;77:579e84.
 Starkstein SE, Ingram L, Garau ML, Mizrahi R. On the overlap between
apathy and depression in dementia. J Neurol Neurosurg Psychiatr 2005;
 Starkstein SE, Leentjens AFG. The nosological position of apathy.
J Neurol Neurosurg Psychiatr 2008 [published online January 10].
 Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R,
Robinson RG. Reliability, validity and clinical correlates of apathy in
Parkinsons’s disease. J Neuropsychiatry Clin Neurosci 1992;4:134e9.
 Starkstein SE, Petracca G, Chemerinski E, Kremer J. Syndromic validity
of apathy in Alzheimer’s disease. Am J Psychiatry 2001;158:872e7.
 Stuss DT, Van Reekum R, Murphy KJ. Differentiation of states and
causes of apathy. 1 ed. New York: Oxford University Press; 2000.
 Van Reekum R, Stuss DT, Ostrander R. Apathy: why care? J Neuropsy
Clin N 2005;17(1):7e19.
 Verghese J, Le Valley A, Derby C, Kuslansky G, Katz M, Hall C, et al.
Leisure activities and the risk of amnestic mild cognitive impairment in
the elderly. Neurology 2006;66(6):821e7.
 Vijayaraghavan L, Krishnamoorthy ES, Brown RG, Trimble MR. Abulia:
a delphi survey of British neurologist and psychiatrist. Mov Disord 2002;
White OB. Negative symptoms: a review of schizophrenia, melancholic
depression and Parkinson’s disease. Brain Res Bull 2006;70:312e21.
 Levy, Dubois. Apathy and the functional anatomy of the prefrontal
cortex-basal ganglia circuits. Cerb Cortex 2006;16(7):916e28.
P. Robert et al. / European Psychiatry 24 (2009) 98e104