APATHY DIAGNOSTIC CRITERIA 2018

CRITERION A Yes No

A quantitative reduction of goal-directed activity either in behavioral, cognitive, emotional or social dimensions in comparison to the patient’s previous level of functioning in these areas. These changes may be reported by the patient himself/herself or by observation of others.

CRITERION B

B1. BEHAVIOUR & COGNITION Loss of, or diminished, goal-directed behaviour or cognitive activity as evidenced by at least one of the following:

Yes No

General level of activity: the patient has a reduced level of activity either at home or work, makes less effort to initiate or accomplish tasks spontaneously, or needs to be prompted to perform them.

Persistence of activity: He/she is less persistent in maintaining an activity or conversation, finding solutions to problems or thinking of alternative ways to accomplish them if they become difficult.

Making choices: He/she has less interest or takes longer to make choices when different alternatives exist (e.g. selecting TV programs, preparing meals, choosing from a menu)

Interest in external issue: He/she has less interest in or reacts less to news, either good or bad, or has less interest in doing new things

Personal wellbeing: He/she is less interested in his/her own health and wellbeing or personal image (general appearance, grooming, clothes, etc.)

B2. EMOTION Loss of, or diminished emotion as evidenced by at least one of the following: Yes No

Spontaneous emotions: the patient shows less spontaneous (self-generated) emotions regarding their own affairs, or appears less interested in events that should matter to him/her or to people that he/she knows well.

Emotional reactions to environment: He/she expresses less emotional reaction in response to positive or negative events in his/her environment that affect him/her or people he/she knows well (e.g., when things go well or bad, responding to jokes, or events on a TV program or a movie, or when disturbed or prompted to do things he/she would prefer not to do).

Impact on others: He/she is less concerned about the impact of his/her actions or feelings on the people around him/her.

Empathy: He/she shows less empathy to the emotions or feelings of others (e.g., becoming happy or sad when someone is happy or sad, or being moved when others need help).

Verbal or physical expressions: He/she shows less verbal or physical reactions that reveal his/her emotional states.

B3. SOCIAL INTERACTION Loss of or diminished, engagement in social interaction as evidenced by at least one of the following:

Yes No

Spontaneous social initiative: the patient takes less initiative in spontaneously proposing social or leisure activities to family or others.

Environmentally stimulated social interaction: He/she participates less, or is less comfortable or more indifferent to social or leisure activities suggested by people around him/her.

Relationship with family members: He/she shows less interest in family members (e.g., to know what is happening to them, to meet them or make arrangements to contact them).

Verbal interaction: He/she is less likely to initiate a conversation, or he/she withdraws soon from it.

Homebound: He / She prefer to stays at home more frequently or longer than usual and shows less interest in getting out to meet people

CRITERION B Yes No

The presence of at least 2 of the 3 dimensions (B1, B2, B3) for a period of at least four weeks and present most of the time

CRITERION C Yes No

These symptoms (A - B) cause clinically significant impairment in personal, social, occupational, or other important areas of functioning.

CRITERION D Yes No

The symptoms (A - B) are not exclusively explained or due to physical disabilities (e.g. blindness and loss of hearing), to motor disabilities, to a diminished level of consciousness, to the direct physiological effects of a substance (e.g. drug of abuse, medication), or to major changes in the patient’s environment.

APATHY DIAGNOSIS Yes No

Positive if criteria A, B, C and D are present.

APPENDIX

Definition: Goal-directed behaviour/ activity: behaviour aimed toward a goal or toward completion of a task Presumed underlying pathophysiological mechanisms: Apathy is the clinical consequence of various underlying dysfunctions of mental and biological processes required to elaborate, initiate and control intentional/goal-directed behaviour.

How to assess apathy

Interviews for caregiver AES-I, NPI, IAS, FrSBe, IA, DAIR, KBCI, LARSi, DAS, APADEM-NH Self report index AES-S, The Behavioural Assessment of Dysexecutive Syndrome, FrSBe, EDA, NPI-C, DAS, AMI Clinician’s scales BPRS, PANSS, SANS, AES-C, UPDRS, The Behavioural Assessment of Dysexecutive Syndrome, IAS, FrSBe, IA, DAIR, LARS, sfLARS, NPI-C

Cautions: Due to anosognosia, take with caution patient’s report. Select a good caregiver; take into account spouse’s biases etc. It is possible in parallel to use other types of scales / assessment tools (eg for depression, anxiety, fatigue..)

Information and Communication technologies (ICT)

There is evidence that apart from the currently used assessment methods for apathy, new ICT approaches could provide clinicians with valuable additional information for detection and therefore more accurate diagnosis of apathy. Actigraphy and methods used to monitor motor activity and rest-activity rhythms had already demonstrated to be accurate and related to apathy. Other methodologies (voice analysis, video analysis, use of serious games) already are used but only at the moment in research setting.

Caution: Such technologies must be used and interpreted with caution in patients with movement disorders (Parkinson’s disease, Huntington’s disease, progressive supranuclear palsy,…). These patients often have reduced total activity, in relation with their motor symptoms. In the same way, they speak slowly, with an hypophonic voice, have a low speech rate due to speech and respiratory disorders. They also have an hypomimic face that can give the impression they do not react to emotion while it is not really the case. Hence, the proposed measures need to be used with reservations. What is needed for pharmacological clinical trials - To provide the scientific rational (biological basis) for targeting specific dimensions; - To provide the relation with the product intended for development (mechanism of action); To provide justification for the choice of endpoint.


The criteria are presented in: European Psychiatry 54 (2018) 71–76

The article and supplements (table 1,2,3) are included below

Original article

Is it time to revise the diagnostic criteria for apathy in brain disorders?The 2018 international consensus group

P. Roberta,*,1, K.L. Lanctôtb,1, L. Agüera-Ortizc, P. Aaltend, F. Bremonda,e, M. Defrancescof,C. Hanong, R. Davidh, B. Duboisi, K. Dujardinj, M. Husaink, A. Könige, R. Levyl,V. Mantuam, D. Meulienn, D. Millero, H.J. Moebiusp, J. Rasmussenq, G. Robertr,M. Ruthirakuhanb, F. Stellas, J. Yesavaget, R. Zegharia, V. Maneraa,eaCoBTeK IA, Memory Centre, University Cote d’Azur, Franceb Sunnybrook Research Institute and Departments of Pharmacology/Toxicology and Psychiatry, University of Toronto, Toronto, CanadacDepartment of Psychiatry, Instituto de Investigacio’n Sanitaria (imas12), Hospital Universitario 12 de Octubre & Centro de Investigacio’n Biome’dica en Redde Salud Mental (CIBERSAM), Madrid, Spaind School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlandse STARS team - INRIA Sophia Antipolis, Valbonne 06902, FrancefDepartment of Psychiatry and Psychotherapy, Innsbruck Medical University, AustriagRegional Resource Centre of Old Age Psychiatry, Paris Descartes University, Assistance Publique-Hôpitaux de Paris, Corentin-Celton Hospital, Issy-les-Moulineaux, FrancehMemory Center CMRR, CHU – CoBTeK lab, University Cote d’Azur, FranceiCentre des Maladies Cognitives et Comportementales (IM2A), Institut du Cerveau et de la Moelle épinière (ICM), UMR-S975, AP-HP, Salpêtrière Hospital,Sorbonne University, Paris, FrancejNeurology and Movement Disorders, Lille University Medical Center, Inserm U1171, Lille, FrancekNuffield Department of Clinical Neurosciences (John Radcliffe Hospital, Oxford OX3 9DU) & Department of Experimental Psychology, University of Oxford, UKlAP-HP, Neurology deparment, Salpetriere hospital Inserm, U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut duCerveau et de la Moelle épinière, ICM, FRONTlab School of medicine, Sorbonne Universités, Paris, FrancemAgenzia Italiana del Farmaco, via del Tritone 181, 00187, Rome, ItalynClinical Research Neurology Lundbeck SAS, DenmarkoBracket, Wayne, PA, USApmoebius-consult GmbH, Baar, ZG, Switzerlandq psi-napse, Surrey, UKr EA4712 "Comportement et noyaux gris centraux", Université de Rennes 1, Frances Laboratorio de Neurociencias LIM27, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de SaoPaulo, UNESP - Univ Estadual Paulista, Biosciences Institute, Campus of Rio Claro, SP, BraziltDepartment of Psychiatry and Behavioral Sciences, Stanford University, School of Medicine, Stanford University, Stanford, CA, USA

A R T I C L E I N F O

Article history:Received 21 April 2018Received in revised form 19 July 2018Accepted 24 July 2018Available online xxx

Keywords:ApathyNeuropsychiatryBrain disordersMotivationBehaviourEmotionSocial interactionTreatment

A B S T R A C T

Background: Apathy is a very common behavioural and psychological symptom across brain disorders. Inthe last decade, there have been considerable advances in research on apathy and motivation. It is thusimportant to revise the apathy diagnostic criteria published in 2009. The main objectives were to: a)revise the definition of apathy; b) update the list of apathy dimensions; c) operationalise the diagnosticcriteria; and d) suggest appropriate assessment tools including new technologies.Methods: The expert panel (N = 23) included researchers and health care professionals working on braindisorders and apathy, a representative of a regulatory body, and a representative of the pharmaceuticalindustry. The revised diagnostic criteria for apathy were developed in a two-step process. First, followingthe standard Delphi methodology, the experts were asked to answer questions via web-survey in tworounds. Second, all the collected information was discussed on the occasion of the 26th EuropeanCongress of Psychiatry held in Nice (France).Results: Apathy was defined as a quantitative reduction of goal-directed activity in comparison to thepatient’s previous level of functioning (criterion A). Symptoms must persist for at least four weeks, andaffect at least two of the three apathy dimensions (behaviour/cognition; emotion; social interaction;

* Corresponding author at: CMRR Institut Claude Pompidou, 10 rue Molière, 06100 Nice, France.E-mail address: probert@unice.fr (P. Robert).

1 Equal contribution.

http://dx.doi.org/10.1016/j.eurpsy.2018.07.0080924-9338/© 2018 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

European Psychiatry 54 (2018) 71–76

Contents lists available at ScienceDirect

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journal homepage: http : / /www.europsy- journal .com

http://crossmark.crossref.org/dialog/?doi=10.1016/j.eurpsy.2018.07.008&domain=pdfmailto:probert@unice.frhttp://dx.doi.org/10.1016/j.eurpsy.2018.07.008http://creativecommons.org/licenses/by-nc-nd/4.0/http://creativecommons.org/licenses/by-nc-nd/4.0/http://dx.doi.org/10.1016/j.eurpsy.2018.07.008http://www.sciencedirect.com/science/journal/09249338http://www.europsy-journal.com

criterion B). Apathy should cause identifiable functional impairments (criterion C), and should not befully explained by other factors, such as effects of a substance or major changes in the patient’senvironment (Criterion D).Conclusions: The new diagnostic criteria for apathy provide a clinical and scientific framework to increasethe validity of apathy as a clinical construct. This should also help to pave the path for apathy in braindisorders to be an interventional target.© 2018 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-

NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

Apathy is a pervasive neuropsychiatric symptom of mostneurocognitive, neurodegenerative, and psychiatric disorders. Itrepresents the most common behavioural and psychologicalsymptom in people with Alzheimer’s disease [1] and Huntington’sdisease [2], and is prevalent in other neurodegenerative con-ditions, such as Parkinson’s disease [3] and vascular dementia [4].It is also found among substantial proportions of individualsfollowing stroke and traumatic brain injury [5], and psychiatricconditions such as major depressive disorder [6] and schizophre-nia [7]. The presence of apathy significantly affects the patient’squality of life [8], and in neurodegenerative disorders is associatedwith a faster cognitive and functional decline [9], representing arisk factor for the conversion from Mild Cognitive Impairment toAlzheimer’s disease [10]. For all these reasons, identifying apathyearly in disease progression is considered a clinical and researchpriority.

In major contributions [11–14], apathy was defined as a lack ofmotivation that persists over time and causes identifiablefunctional impairment. Three dimensions of apathy were identi-fied, including deficits in goal-directed behaviour, goal-directedcognitive activity, and emotions. In 2008, a task force was set upduring the European Psychiatric Association congress to developdiagnostic criteria for apathy [15]. Based on these diagnosticcriteria, a patient is classified as apathetic when he/she meets fourcriteria (A-D). Criterion A specifies the presence of a loss of (ordiminished) motivation in comparison to the person’s previouslevel of functioning, which is not consistent with his age or culture.These changes in motivation may be reported by the patienthimself or by the observations of others. Criterion B stipulates thepresence of symptoms in at least two of three domains (behaviour,cognition, and emotion) for a period of at least four weeks andpresent most of the time. These symptoms can be detected eitherin self-initiated or environment-stimulated activities. Criterion Cspecifies that the symptoms (A - B) must cause clinically significantimpairment in personal, social, occupational domains, or otherimportant areas of functioning. Finally, Criterion D specifies thatthe symptoms (A - B) should not exclusively explained or due tophysical or motor disabilities, to diminished level of consciousnessor to the direct physiological effects of a substance.

These diagnostic criteria for apathy are now widely used inclinical and research practice for patients with neurodegenerativeand neuropsychiatric disorders (e.g., [16]).

In the last decade, there have been considerable advances in thedomain of apathy in brain disorders, including the apathybiological and neural based (e.g., [17]). First, the definition ofapathy as a disorder of ‘motivation’ (Criterion A) has beenextensively criticized (e.g. [18],), as ‘motivation’ is a psychologicalinterpretation of behavioural internal states, which may bedifficult to measure objectively. At the same time, the constructof goal directed behaviour/activity - construed as a set of relatedprocesses by which an internal state is translated, throughobservable action, into the attainment of a goal (e.g., [19]) - isincreasingly used in the domain of neuroscience, and it has beenproposed to be a useful to operationalize apathy, particularly in

clinical contexts. Second, the different apathy domains (criterionB) have been object of discussion, and most particularly: a) thedistinction between the ‘behaviour’ and ‘cognition’ domains andits relevance in clinical practice [20]; b) the importance of addingthe ‘social interaction’ as a domain of apathy [21]; c) theimportance of considering alternative proposals on apathy sub-types based on the underlying disrupted mechanisms (for instance,the ‘emotional–affective’, ‘cognitive’ and ‘auto-activation’ apathysubtypes [18]. Third, finer assessment tools for apathy have beendeveloped, based on classical instruments (e.g., interviews andself-reports; see [17] for a review) but also on new Information andCommunication Technologies (ICTs, e.g., [22]). However, noconsensus has been reached so far on the role of ICTs in theapathy assessment, and on their relations to classical apathymeasures.

Finally, the therapeutic strategy is an important aspect toconsider. Despite the lack of an established pharmacologicaltreatment for apathy with a strong evidence base (e.g., [23]),preliminary data on apathy treatment efficacy are emerging [24],with a research focus on drugs [25] and repetitive transcranialmagnetic stimulation [26], often accompanied by non-pharmaco-logical approaches [27]. Having diagnostic criteria for apathy basedon the last advancements in the clinical research that reach a wideconsensus among the scientific, regulatory and medical commu-nity is therefore crucial. These would, for example, allow clinicaltrials to be designed with a well-defined population and moresensitive apathy outcome measures, and thus obtain wideracceptance regarding the effectiveness of prevention and/ortreatment strategies.

Given all these advances, a group of experts in the domain ofapathy in brain disorders (leaded by PR and KL) decided to revisethe diagnostic criteria for apathy proposed in 2008. The mainobjectives were to: a) revise the definition of apathy (criterion A);b) update the list of apathy dimensions (criterion B); c) operation-alize the diagnostic criteria using examples of clinical situationsand areas of possible impairment (criterion B); and d) suggestappropriate and updated apathy assessment tools.

2. Methods

2.1. Task force

Participants were selected based on their expertise in thedomain of apathy in brain disorders. Some of these experts alreadyparticipated to the 2008 expert meeting. These included, amongothers, clinicians and researchers from a) the CoBTeK-IA lab andMemory centre of the University Côte d’Azur, a lab with a focus onhow to assess apathy using ICT); b) the French Memory Centrenetwork, which includes 17 research memory centres located inthe French university hospitals, c) the ISCTM (International Societyfor CNS Clinical Trials and Methodology) Apathy Workgroup; d) theISTAART (International Society to Advance Alzheimer's Researchand Treatment) Neuropsychiatric symptoms professional InterestArea.

The final task force included 23 experts (researchers, healthcare professionals and representatives of one regulatory body and

72 P. Robert et al. / European Psychiatry 54 (2018) 71–76

http://creativecommons.org/licenses/by-nc-nd/4.0/

of the pharmaceutical industry). The complete list of the experts,together with their field of expertise, is reported in STable 1.

Following the standard Delphi methodology [28], the reviseddiagnostic criteria for apathy were developed in a two-stepprocess: web-surveys followed by a consensus meeting.

2.2. Web-surveys

The experts were asked to answer questions via web-survey intwo rounds (between November 2017 and February 2018). Aftereach round, a facilitator (PR) provided a summary of the experts’responses, and encouraged the experts to analyze, comment and(eventually) revise their earlier responses in light of thecommentaries of other members of the panel. The questions forthe second round were designed according to the responsesobtained in the first round. In addition, between the first andsecond round, the experts were asked to work in subgroups inorder to focus on different topics (generate definitions, findrelevant examples in the clinical practice, indicate the potential toemploy new technologies). After the second round, a first draft ofthe new criteria, including the elements of the two rounds and thedocuments provided by the subgroups, were circulated among allthe experts. A shortened version of the questionnaire (questions 1to 4) was also sent to the French Memory Centers network, whichincludes 17 research memory centers located in the Frenchuniversity hospital. Responses were obtained from 11 centers(64%).

2.3. Final consensus meeting

The two web-survey results and the open discussion pointswere revised by the task force during the 26th European Congress

of Psychiatry held on March 5, 2018 in Nice (France). A consensuswas reached when all participants agreed on the decision tomodify (or not) specific aspects of the current diagnostic criteriafor apathy.

3. Results

The new proposed diagnostic criteria for apathy, to beemployed both in the clinical and the research domain, arereported in Table 1 and in the Appendix (SupplementaryMaterials). The list of questions and responses for the two web-surveys are reported in STable 2 (responses obtained from 17participants).

3.1. Title

Diagnostic Criteria for Apathy. No modification was performedto be consistent with the previous literature.

3.2. Criterion A

This stipulates the presence of quantitative reduction of goal-directed activity either in the behavioural, cognitive, emotional orsocial dimension in comparison to the patient’s previous level offunctioning. These changes may be reported by the patient him/herself or by the observation of others.

Modifications: 1) The term ‘motivation’ was replaced by ‘goal-directed behaviour/activity’, which is easier to observe andobjectively quantify (see [18]). 2) The sentence ‘which is notconsistent with his/her age or culture’ was removed, as it wasconsidered unnecessary (as apathy is defined as a reductioncompared to the person’s previous level of functioning); 3) the

Table 1Apathy diagnostic criteria 2018.

CRITERION A: A quantitative reduction of goal-directed activity either in behavioral, cognitive, emotional or social dimensions in comparison to the patient’s previouslevel of functioning in these areas. These changes may be reported by the patient himself/herself or by observation of others.

CRITERION B: The presence of at least 2 of the 3 following dimensions for a period of at least four weeks and present most of the timeB1. BEHAVIOUR & COGNITIONLoss of, or diminished, goal-directed behaviour or cognitive activity as evidenced by at least one of the following:General level of activity: the patient has a reduced level of activity either at home or work, makes less effort to initiate or accomplish tasks spontaneously, or needs tobe prompted to perform them.Persistence of activity: He/she is less persistent in maintaining an activity or conversation, finding solutions to problems or thinking of alternative ways to accomplishthem if they become difficult.Making choices: He/she has less interest or takes longer to make choices when different alternatives exist (e.g., selecting TV programs, preparing meals, choosing froma menu, etc.)Interest in external issue: He/she has less interest in or reacts less to news, either good or bad, or has less interest in doing new thingsPersonal wellbeing: He/she is less interested in his/her own health and wellbeing or personal image (general appearance, grooming, clothes, etc.).B2. EMOTIONLoss of, or diminished, emotion as evidenced by at least one of the following:Spontaneous emotions: the patient shows less spontaneous (self-generated) emotions regarding their own affairs, or appears less interested in events that shouldmatter to him/her or to people that he/she knows well.Emotional reactions to environment: He/she expresses less emotional reaction in response to positive or negative events in his/her environment that affect him/heror people he/she knows well (e.g., when things go well or bad, responding to jokes, or events on a TV program or a movie, or when disturbed or prompted to do thingshe/she would prefer not to do).Impact on others: He/she is less concerned about the impact of his/her actions or feelings on the people around him/her.Empathy: He/she shows less empathy to the emotions or feelings of others (e.g., becoming happy or sad when someone is happy or sad, or being moved when othersneed help).Verbal or physical expressions: He/she shows less verbal or physical reactions that reveal his/her emotional states.B3. SOCIAL INTERACTION Loss of, or diminished engagement in social interaction as evidenced by at least one of the following:Spontaneous social initiative: the patient takes less initiative in spontaneously proposing social or leisure activities to family or others.Environmentally stimulated social interaction: He/she participates less, or is less comfortable or more indifferent to social or leisure activities suggested by peoplearound him/her.Relationship with family members: He/she shows less interest in family members (e.g., to know what is happening to them, to meet them or make arrangements tocontact them).Verbal interaction: He/she is less likely to initiate a conversation, or he/she withdraws soon from itHomebound: He /She prefer to stays at home more frequently or longer than usual and shows less interest in getting out to meet people.

CRITERION C These symptoms (A - B) cause clinically significant impairment in personal, social, occupational, or other important areas of functioning.CRITERION D The symptoms (A - B) are not exclusively explained or due to physical disabilities (e.g. blindness and loss of hearing), to motor disabilities, to a diminishedlevel of consciousness, to the direct physiological effects of a substance (e.g. drug of abuse, medication), or to major changes in the patient’s environment.

P. Robert et al. / European Psychiatry 54 (2018) 71–76 73

different apathy dimensions were listed in the definition (thebehavioural, cognitive, emotional or social dimensions), to specifyimmediately the relevant domains.

3.3. Criterion B

This indicates that apathy is a persistent state, rather than atransient or intermittent one by incorporating in the definition aminimum duration of four weeks [29]. It also stipulates thatsymptoms should be observed in at least 2 out of the following 3dimensions:

3.3.1. Behaviour & cognitionThis includes the loss of, or diminished, goal-directed behaviour

and cognitive activity as evidenced by at least one of 5 examples /situations. This domain embeds the loss of, or diminished, goal-directed behaviour, i.e., a reduction in routine (habitual) and non-routine (occasional) activities, and a reduced goal-directedcognitive activity, usually interpreted in practical terms as a lossof, or diminished, interests.

3.3.2. EmotionThis included the loss of, or diminished, emotion as evidenced

by at least one of 5 examples/situations including both spontane-ous emotions, and emotions in response to the environment/others.

3.3.3. Social interactionThis refers to the loss of, or diminished, engagement in social

interaction as evidenced by at least one of 5 examples/situations.These include both spontaneous social initiative, and environ-ment/others stimulated social interaction.

Modifications: 1) the term ‘domains’ was replaced with‘dimensions’, as there is some overlap between behaviour/cognition, emotion and social interaction areas. 2) The apathydimensions were modified (previous dimensions: Cognition;Behavior; Emotion). First, as deficits in ‘Behavior’ and ‘Cognition’were found to be frequently associated in the clinical practice andin large studies (e.g., [20]) it was agreed that these two dimensionscould be included in a single category. Furthermore, it was agreedthat it is important to add the ‘Social interaction’ dimension. Thefact that impaired social interaction is an important domain ofapathy has been previously highlighted by Sockeel and colleaguesduring the development of the LARS scale [29]. There is nowconverging evidence that the social dimension may represent aseparate apathy domain, distinct from cognition/behaviour andemotion [30–33, 34]. 3). The difference between self-initiated andenvironmentally stimulated deficits was presented in the exam-ples provided for each dimension, instead of being part of the maindefinition. 4) Areas of impairment (five examples per dimension)were added. This was considered as important to help clinicians intheir everyday practice, and to help to operationalize thediagnostic criteria. The examples were drafted by a sub-group ofexperts based on their clinical experience, and validated by all theexperts task force.

3.4. Criterion C

This refers to the presence of clinically significant functionalimpairment (e.g., in personal, social and/or occupational domains)largely attributable to the symptoms specified in criteria A and B.No modification was performed.

3.5. Criterion D

The intent is to exclude from the definition conditions andstates that might not be distinguished from apathy solely on thebasis of the criteria above (e.g., diminished level of consciousness),as well as transient states of apathy that can be attributed to adiscrete non-neuropsychiatric cause (e.g., direct physiologicaleffects of a drug/medication). This criterion also suggests takinginto account whether major changes in the patient’s environmentoccurred (e.g., severe conflicts, loss of significant people), thatmight completely explain the observed symptoms.

Modifications: The following sentence was added “The symp-toms (A–B) are not exclusively explained or due to major changesin the patient’s environment”. This was decided after acknowledg-ing that major environmental events, such as a terrorist attack,may lead to major changes in several aspects of everyday life thatmay mimic apathy (e.g., social isolation, emotional blunting,reduction of activities outside).

3.6. Appendices

The appendices (available online as Supplementary Materials aswell as in the criteria at the following link: http://www.innovation-alzheimer.fr/wp-content/uploads/downloads/2018/04/Apathy-Criteria-2018.pdf) includes the following elements:

1 A definition of Goal-directed behaviour/activity: This sectiondefines goal-directed behaviour/activity as behaviour aimedtoward a goal or toward the completion of a task. It alsoconsiders the presumed pathophysiological mechanisms un-derpinning apathy as being the consequence of variousunderlying dysfunctions of mental and biological processesrequired to elaborate, initiate and control intentional/goal-directed behaviour).

2 A summary of the main instruments that can be employed toassess apathy. Specifically, apathy can be assessed through:a) A number of clinical scales and indexes (e.g., [16]), based on

the patient’s self-reports, and/or informant-based scales andindexes, and/or clinician’s scales. STable 3 reports theselected clinical scales/indexes available, specifying whetherthey include a patient, informant and/or clinician version; theapathy dimensions that each instrument assesses, and thepopulation for which the instrument was initially designed/tested.

b) New Information and Communication Technologies (ICT).There is emerging evidence that new ICT approaches couldprovide clinicians with valuable additional information interms of assessment, and therefore more accurate diagnosisof apathy (e.g., [22]). ICT instruments that could be employedto assess different aspects and dimensions of apathy include:actigraphy and methods used to monitor motor activity andrest-activity rhythms (e.g., [35]); voice analysis, videoanalysis, serious games, and robots, which are alreadydeveloped, but currently employed only in research settings(e.g. [36],).

Some cautions were also added. For instance, regarding clinicalscales, it was reported that, due to anosognosia, patient’s reportsshould be taken with caution. Regarding the caregiver’s reports, itis important to select a reliable caregiver (e.g., someone whospends sufficient time with the patient, and is able to provide anaccurate evaluation) as well as taking into account their potentialbiases. It is possible to use other types of scales / assessment toolsin parallel to assess co-morbidities (e.g., for depression, anxiety,fatigue). Concerning ICT, results should be interpreted with cautionin patients with movement disorders who may show poverty of

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movement in the absence of apathy (e.g., Parkinson’s disease,Huntington’s disease, progressive supranuclear palsy). Thesepatients often have reduced total activity, related to their motorsymptoms. Likewise, they may speak slowly, with a hypophonicvoice, have low speech rates due to speech and respiratory deficits;or have a hypomimic face that can give the erroneous impressionthat they do not have emotional reactions.

3 A summary of what is needed for pharmacological clinical trials.This includes providing: a) the scientific rationale (biologicalbasis) for targeting specific dimensions; b) the relation with theproduct intended for development (mechanism of action); c)justification for the selection of clinical trial endpoints (seediscussion).

4. Discussion

Recent literature points to the importance of adopting a transdiagnostic approach, which cuts across traditional diseaseboundaries, to provide useful means for better understanding ofapathy and related conditions [37]. Reaching a wide, internationalconsensus on the definition and dimensions of apathy is a crucialstep in this direction. The expert panel that worked to develop the2018 diagnostic criteria for apathy involved clinicians working ondifferent brain disorders, including Alzheimer’s disease and otherneurodegenerative disorders, major depression and schizophrenia.Similarly, it involved people from different disciplines, such asadult and geriatric psychiatry, neurology, neuropsychopharmacol-ogy, informatics and technology as well as people from thepharmaceutical industry and from the regulatory domain. For thisreason, we are convinced that the 2018 apathy criteria may have animpact on the clinical and research community.

The 2018 apathy diagnostic criteria keep the same overallstructure (criteria A–D) compared to the previous criteria [15].However major modifications were performed. Specifically:

Criterion A: the term motivation was replaced by goal-directedbehavior. This was a pragmatic choice, because ‘goal-directedbehaviors’ are easier to observe and describe compared tomotivation, which is an internal state that can only be inferredfrom behaviour observation. This is also in line with the recentscientific literature [18].

Criterion B: the expert panel faced the challenge of keeping thesame 3-dimentions structures. This is for pragmatic reasons, as thediagnostic criteria should be easy and fast to assess in the clinicalpractice. At the same time, it was important to include a broaderspectrum of symptoms, in particular related to the socialinteraction aspects. This led to add ‘social interaction’ as a separatedimension (B3), and for practical and theoretical reasons, tosubsume behavioral and cognitive domains of apathy under onecategory (B1). This association could be criticised because thecategory ‘behavior-cognition’ is very broad, and puts togethersymptoms that can potentially be dissociated based on theunderling brain processes (e.g., [38,39]). However, in the clinicalpractice, it is difficult to dissociate cognitive from behavioraldeficits, because both result in diminished observable activity. Therevision of the diagnostic criteria is not primarily meant for basicresearch purposes; it is mainly meant to improve the clinicaldescription, and thus the assessment of apathy across braindisorders in the domain of clinical research and the everydayclinical practice. In this domain the association between ‘behavior’and ‘cognition’ makes sense. The clinical focus also explains whythe dimensions included in the present criteria do not totallyoverlap with the sub-forms of apathy described by Levy and Dubois[18], that is the ‘emotional-affective, cognitive’ and 'auto-activa-tion' subtypes. That classification relies on potential mechanisms

underlying apathy, while the classification presented here refers tothe dimensions for which impairment can be observed at theclinical level. The focus on designing more understandable andeasy to use criteria also justifies the efforts done for operation-alizing each domain with the same number of examples. In the caseof the B1 dimension, these include both cognitive and behavioralaspects. Furthermore, the examples systematically include symp-toms related to activity self-initiation, and to activities in responseto the environment stimulation.

The validation of these criteria in clinical practice willdetermine if this 3-dimension structure is meaningful, and whichare the most frequent examples found for each dimension.

As in the previous diagnostic systems, the presence ofimpairment in at least two dimensions is needed to fulfill criterionB. This allows the possibility that some patients with a deficit in asingle apathy dimension are not classified as apathetic. It isimportant to keep track of these single-dimension deficits, mostparticularly for the early pathologies stages, in order to betterunderstand if there is a continuum between single symptoms andapparition of a full apathy spectrum. This is of interest in the field ofAD and related disorders, but also in other neuropsychiatricdiseases.

In parallel to facilitate the ease of use in the clinical practice, oneof the major challenges of the new criteria is to pave the path forthe use of new technologies in the assessment domain. This is truefor apathy but also for other neuropsychiatric symptoms. Theassessment methods will improve and become more objectivethanks to ICT. This is why the present apathy criteria providesymptoms descriptions as objective as possible, and encompassingthe overall spectrum of symptoms. Today, despite some limi-tations, the motor activity assessment seems the most robustmethod, as reported in the Appendix found in theSupplementaryMaterials (e.g., [40,41]). But, in the next future, emergingtechnologies such as audio and video sensors could be part ofthe clinicians’ choice options (e.g. [36],).

The new criteria should also provide additional elements toinform the choice of non-pharmacological treatments targeted to aspecific patient. For instance, examples were included for eachdimension to help to indicate if the symptoms concernedspontaneous behavior, or the behavior in response to other peopleor the environment.

We are convinced that the 2018 apathy diagnostic criteria mayalso be important to provide more objective and internationallyrecognized criteria for apathy assessment for pharmacologicaltherapeutic research. Despite the lack of biological or molecularunderstanding of many of the phenomenological domains in thecontext of major psychiatric or neurological categories, regulatoryscience is moving towards a dimensional approach to drug targets.Phenomenological domains can be described within or acrossdiagnostic entities. In order to accept a phenomenological domainas a drug target, a rationale should be provided for the validity of itsconstruct and the value for the patients. The new diagnosticcriteria for apathy provide a clinical and scientific framework toincrease the validity and the value of apathy as a clinical construct.Since the present revision of the diagnostic criteria considersapathy as a domain that exists across clinical diagnoses such asmajor and mild neurocognitive disorders, schizophrenia and majordepression, the consistency of the evaluation should be demon-strated independently from the population in which the assess-ment is carried out. As a general regulatory requirement, clinicaltrials designed to test a specific hypothesis of efficacy on apathy inthe context of a specific diagnostic category are required, as well asadequate endpoints. Also, depending on whether apathy istargeted in the context of dementia, or schizophrenia or majordepression, the relationship with the time course of the underlying

P. Robert et al. / European Psychiatry 54 (2018) 71–76 75

pathology should be established. Adequate justification why theproduct has the potential to improve apathy will be needed.

Acknowledgments and authors’ note

The expert meeting and the Delphi panel were supported by theEdmond & Lily Safra Foundation, Institute Claude Pompidou,University Côte d’Azur, and by the IA association. Thanks for theISTCM and ISTAART contribution, and a special acknowledgment toall clinicians and researchers working for so many years on thetopic. The apathy diagnostic is part of the MNC3 programUniversity Cote d’Azur.

Valentine Mantua: The opinions expressed in this manuscriptare the personal views of the Author and may not be understood orquoted as being made on behalf of or reflecting the position of theItalian (AIFA) or European (EMA) Medicines Agency or any of theirCommittees. The mention of commercial products, their sources,or their use in connection with material reported herein is not to beconstructed as either an actual or implied endorsement of suchproducts by any Public Department or Health and/or PayerServices.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, inthe online version, at https://doi.org/10.1016/j.eurpsy.2018.07.008.

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Supplementary Table 1. Participants in the expert panel

Name Domain of expertise

P.Robert*1, K. L. Lanctôt*2

Experts in the field of apathy in Europe and North America. Philippe Robert organized the 2008 expert meeting, and Krista Lanctot is expert in pharmacological approaches. She makes the link with other scientific association involved in clinical trials (ISTCM and ISTAART).

L. Agüera-Ortiz3, P. Aalten4,

C.Hanon7, R.David8, B.Dubois9, K. Dujardin10, M. Husain11, A. König5, R. Levy12 V. Manera 1,5, F.Stella19, J. Yesavage20

Clinicians and researchers experts in apathy and behavioral disturbances.

F. Bremond1,5

Engineer in informatics and specialist of the use of ICT for the assessment of behavioral disturbances.

G., M. Ruthirakuhan2, R. Zeghari1

PhD students in Nice and in Toronto working directly for their thesis on apathy.

M. Defrancesco6, D. Meulien14, D. Miller15, H.J. Moebius16, J. Rasmussen17

Experts belonging to the ISTCM and ISTAART groups.

V. Mantua13

Expert in an European agency. Please take note that the opinions expressed in this manuscript are the personal views of the Author and may not be understood or quoted as being made on behalf of or reflecting the position of the Italian (AIFA) or European (EMA) Medicines Agency or any of their Committees. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be constructed as either an actual or implied endorsement of such products by any Public Department or Health and/or Payer Services.

Affiliations 1 CoBTeK IA, Memory centre, University Cote d’Azur France 2 Sunnybrook Research Institute and Departments of Pharmacology/Toxicology and Psychiatry, University of Toronto, Toronto, Canada 3 Department of Psychiatry. Instituto de Investigación Sanitaria (imas12), Hospital Universitario 12 de Octubre & Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain 4 School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht

5 STARS team - INRIA Sophia Antipolis, Valbonne 06902, France

6 Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Austria

7 Regional Resource Centre of Old Age Psychiatry, Paris Descartes University, Assistance Publique-Hôpitaux de Paris, Corentin-Celton Hospital, Issy-les-Moulineaux, France 8 Memory Center CMRR, CHU – CoBTeK lab, University Cote d’Azur France 9 Centre des Maladies Cognitives et Comportementales (IM2A), Institut du Cerveau et de la Moelle épinière (ICM), UMR-S975, AP-HP, Salpêtrière Hospital, Sorbonne University, Paris, France 10 Neurology and movement disorders, Lille university medical center, Inserm U1171, Lille, France 11 Nuffield Department of Clinical Neurosciences (John Radcliffe Hospital, Oxford OX3 9DU) & Department of Experimental Psychology, University of Oxford, UK

12 AP-HP, Neurology deparment, Salpetriere hospital Inserm, U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, FRONTlab School of medicine, Sorbonne Universités. Paris, France

13 Agenzia Italiana del Farmaco, via del Tritone 181, 00187, Rome, Italy 14 Clinical Research Neurology Lundbeck SAS, Denmark 15 Bracket, Wayne, PA, USA 16 moebius-consult GmbH, Baar (ZG), Switzerland 17 psi-napse, Surrey, UK 18 EA4712 "Comportement et noyaux gris centraux", Université de Rennes1, France 19 Laboratorio de Neurociencias LIM27, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, UNESP - Univ Estadual Paulista, Biosciences Institute, Campus of Rio Claro, SP, Brazil 20 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine,Stanford University,Stanford,CA,USA

Supplementary Table 2: Delphi round 1 and 2; Questions, and responses obtained from the expert panel and from clinicians belonging to the French Research Memory Centre network

Round 1 General questions Experts

Score* (Mean, SD) / 5

Clinicians Score** (Mean, SD) / 5

1. How important is it to have apathy diagnostic criteria for The clinical practice 4.4 (.7) 3.6 (.7) Research 4.8 (.4) 4.2 (.8) 2. For clinical purposes, how important are the diagnostic criteria for the following targets?

To improve prevention strategies 4.3 (.8) 3.0 (.8) To improve diagnostic and assessment strategies 4.7 (.5) 3.8 (.8) To help clinicians in the choice of the

pharmacologic treatments 4.2 (1.0) 3.5 (.7)

To help clinicians in the choice of the non pharmacologic treatments

4.2 (.9) 3.8 (.6)

To help family caregivers to understand the pathology and put in place care strategies

4.0 (1.0) 4.0 (.6)

To help professional caregivers to understand the pathology and put in place care strategies

4.1 (.8) 3.9 (.7)

3. For research purposes, how important are the diagnostic criteria for the following targets?

To improve the understanding of the phenomenology

4.5 (.6) 4.1 (.9)

To improve the understanding of the neuroanatomical and biological correlates

4.6 (.5) 4.2 (.8)

To improve the population selection criteria in pharmacological clinical trials

4.7 (.8) 4.4 (.8)

To improve the population selection criteria in non-pharmacological clinical trials

4.6 (.6) 4.3 (.9)

Criteria specific questions % of responses (17 responses)

% of responses (11 responses)

4a. Title: Is it important to modify the title and to replace apathy with another terminology?

Yes 65 63 No 35 27 Don’t know / Prefer not to answer 0 10 4b. If so, what terminology would you suggest employing? Motivation deficits 17.5 0 Motivation disorders 17.5 67 N/A, Don’t know / Prefer not to answer/Other 65 33 5. Criterion A: do you agree with the current formulation? Yes 70 No 30 Don’t know / Prefer not to answer 0 6. Criterion B: do you agree to simplify and rephrase the difference between self-initiation and environment stimulated events?

Yes 65 No 12 Consider 2 versions of the criteria (1 for clinical

purposes, 1 for research) 18

Don’t know / Prefer not to answer 5 7. Criterion B: do you agree to add questions for the criteria operationalization?

Yes 76

No 12 Don’t know / Prefer not to answer 12 8. Criteria C: This criterion indicates that the criteria are not only related to the dementia field. Is it important to keep this specification?

Yes 65 No 24 Don’t know / Prefer not to answer 12 Round 2 % of responses

(10 responses) 9. The majority of responses indicated to keep the term apathy in the title. If it is possible to have a subtitle, which one would you suggest?

Motivation disorders 20 Motivation deficits 80 10. Criterion A: The majority of responses indicated to keep the current definition. Some alternatives were also suggested: do you agree with the following?

To replace “motivation” with “motivation and drive” 17 To replace “motivation” with “goal-directed

behaviour” 67

To replace “functioning” with “performance” 17 To specify the domains included in criterion B 50 11. Do you agree to include in the diagnostic criteria document a brief glossary in order to define: “motivation”, “goal-directed behaviour” and other notions of interest?

Yes 100 No 0 12. Criterion B: The majority of responses indicated to simplify and rephrase the difference between self-initiation and environment stimulated events, and to add questions for the criteria operationalization (same number of examples). Furthermore, some important modifications were suggested. Please indicate if you agree with the following proposals:

If there is the presence of environment-stimulated deficits (no reaction to environmental stimuli), indicate a higher degree of apathy

62.5

Modify the 3 present domains (1/Cognition; 2/Behaviour; 3/Emotion) with the following domains: 1/ Behaviour-Cognition; 2/ Emotion; 3/ Social interaction

62.5

13. Criterion C: The majority of responses indicated that is important to keep the indication that the criteria are not only related to dementia. This underlines the dimensional level of the diagnostic criteria. More generally this raises the question of the criteria use for various disorders (eg dementia, non dementia), users (clinician, researchers), practices (daily clinic, research, clinical trials). Do you agree with the following proposals?

To have 2 levels of descriptions (1 for the clinical practice, 1 for research)

12.5

To add in the annex suggestions on how to assess the different apathy domains (including caregiver’s scales, ICT, etc.)

87.5

To add in the annex indications according to the type of disorder

75

Quantitative rating for general questions: 5-point rating scale: 1= Not important at all; 2= Not very important; 3= Important; 4= Very important; 5= Extremely important. * Expert’s scores: scores provided by the participants of the expert meeting (N=17).

** Clinician’s scores: scores provided by clinicians belonging to the French Research Memory Centre network (responses obtained by 11 out of the 17 centres).

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Supplementary Table 3: Apathy Scales and interviews

Scale for: Apathy dimensions* Apathy specific **

Original study population

Brief Psychiatric Rating Scale (BPRS)

[1] Overall and Gorham (1962) Clinician

Emotion No

Paranoia Schizophrenia

Depression

Positive and Negative Syndrome Scale (PANSS)

[2] Kay et al. (1987) Clinician

Emotion, Social Interaction No

Schizophrenia

Scale for the Assessment of Negative Symptoms (SANS)

[3] Andreasen (1989) Clinician

Emotion, Social interaction No

Schizophrenia

Apathy Evaluation Scale (AES-S/I/C)

[4] Marin et al. (1991)

Self-report Caregiver Clinician

Cognition, Behavior, Emotion Yes

AD (Alzheimer’s disease), Brain injury,

Major depression

Apathy Scale (AS) [5] Starkstein et al. (1992)

Clinician Cognition, Behavior, Emotion

Yes PD (Parkinson’s disease)

Neuropsychiatric Inventory NPI [6] Cummings et al. (1994)

Caregiver Cognition, Behavior, Emotion

No Dementia

Unified Parkinson’s Disease Rating Scale (UPDRS) 1 item

[7] Martinez-Sarriez et al. (1994)

Clinician Cognition, Behavior

No PD

The Behavioural Assessment of Dysexecutive Syndrome- DEX

[8] Wilson et al. (1996) Clinician

Self-report Cognition, Behavior, Emotion

No Brain injury

Irritability-Apathy Scale (IAS) [9] Burns et al. (1997)

Caregiver Clinician

Cognition, Behavior No

AD HD (Huntington disease)

Frontal Lobe Personality Scale (FLOPS) now known as the

Frontal Systems Behavior Scale (FrSBe)

[10] Grace et al. (1999)

Self-report Caregiver Clinician

Cognition, Behavior No

Brain injury (frontal lobe)

NPIa-Q [11] Kaufer et al. (2000)

Caregiver Cognition, Behavior, Emotion

No AD

2

L’échelle d’appréciation de la démotivation (EDA)

[12] Chantoin et al. (2001) Self-report

Cognition, Behavior, Emotion Yes

Dementia (especially memory disorders)

Apathy Inventory (AI) [13] Robert et al. (2002)

Caregiver Clinician

Cognition, Behavior, Emotion Yes

Dementia

Dementia Apathy Interview and Rating (DAIR)

[14] Strauss & Sperry (2002)

Caregiver Clinician

Behavior No

Dementia

Key Behavior Change Inventory (KBCI)

[15] Belanger et al. (2002) Caregiver

Cognition, Behavior, Emotion No

Elderly memory disorder

Lille Apathy Rating Scale (LARS)

[16] Sockeel et al. (2006) Lille Apathy Rating Scale

short form (sfLARS) [17] Dujardin et al. (2013)

Clinician Cognition, Behavior, Emotion, Social

Interaction Yes

PD

[18] Informant based Lille apathy rating scale (LARS-i)

Dujardin et al. (2008) Caregiver

Cognition, Behavior, Emotion, Social Interaction

Yes PD

Neuropsychiatric Inventory NPI-C

[19] de Medeiros et al (2010) Clinician

Behavior, Cognition, Emotion No

Dementia

Abbreviated apathy evaluation scale (AES-10)

[20] Leontjevas et al. (2012) Caregiver Cognition, Behavior, Emotion Yes Dementia

Apathy in institutionalized persons with dementia

APADEM-NH [21] Aguera-Ortiz & al (2015)

Caregiver Cognition, Behavior, Emotion

Yes

Dementia

Dimensional Apathy Scale (DAS)

[22a,b] Radakovic et Abrahams (2014)

Self-report Caregiver

Cognition, Behavior, Emotion, Yes

Neurodegenerative diseases*** ALS,PD, AD

Apathy motivation index [23] Ang et al. (2017)

Self-report Cognition, Behavior, Emotion, Social

Interaction Yes

Healthy adults

* Based on the following classification coming from the Apathy diagnostic criteria 2018: Behavior & Cognition; Emotion; Social interaction. ** Yes = the scale is apathy specific. No = the scale assesses apathy as a subdomain. *** ALS (amyotrophic lateral sclerosis), PD (Parkinson’s Disease) AD (Alzheimer’s Disease)

The scale also proposed a Dimensional Apathy Framework. Furthermore, the discrepancy between self-ratings and informant/carer-ratings on the DAS have been used to define the awareness deficit in dementia, and are described in the below papers:

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Radakovic, R., Starr, J. M., & Abrahams, S. (2017). A novel assessment and profiling of multidimensional apathy in Alzheimer’s disease. Journal of Alzheimer's Disease, 60(1), 57-67.

Radakovic, R., & Abrahams, S. (2018). Multidimensional apathy: evidence from neurodegenerative disease. Current Opinion in Behavioral Sciences, 22, 42-49.

References [1] J. Overall and D. Gorham, The Brief Psychiatric Rating ScalePsychological Reports.brief

psychiatric rating scale, Psychol Rep 10 (3), 1962, 799–812. [2] S. Kay, A. Fiszbein and L. Opler, The Positive and Negative Syndrome Scale (PANSS) for

Spositive and negative syndrome scale (PANSS) for schizophrenia, Schizophrenia Bulletin. Bull 13 (2), 1987, 261–276.

[3] N.C. Andreasen, The Scale for the Assessment of Negative Symptoms (SANS): conceptual and theoretical foundations, Br J Psychiatry Suppl (.November (7)), 1989, 49–58.

[4] R. Marin, R. Biedrzycki and S. Firinciogullari, Reliability and validity of the apathy evaluation scale, Psychiatry Res earch.38 (2), 1991, 143–162.

[5] S. Starksein, H. Mayberg, T. Preziosi, P. Andrezejewski, R. Leiguarda and R. Robinson, Reliability, validity, and clinical correlates of apathy in Parkinson’s disease, The Journal of Neuropsychiatry and Clinical Neurosciences.J Neuropsychiatry Clin Neurosci 4 (2), 1992, 134–139.

[6] J. Cummings, M. Mega, K. Gray, S. Rosenberg-Thompson, D. Carusi and J. Gornbein, The Neuropsychiatric Inventory: Ccomprehensive assessment of psychopathology in dementia, Neurology .44 (12), 1994, 2308-2308.

[7] P. Martínez-Martín, A. Gil-Nagel, L.M. Gracia, J.B. Gómez, J. Martínez-Sarriés, et al., F.BermejoUnified Parkinson’s Disease Rating SUnified parkinson’s disease rating scale characteristics and structure, The CooperativeCoop Multicentric Group. Mov Disord. 9 (Januray (1)), 1994, 76–83.

[8] B. Wilson, J. Evans, N. Alderman, P. Burgess and H. Emilie, Behavioural assessment of the dysexecutive syndrome, In: P. Rabbitt, (Ed), Methodology of frontal and executive function, 1997, 239–250.

[9] A. Burns, S. Folstein, J. Brandt and M. Folstein, Clinical Assessment of Irritability, Aggression, and Aassessment of irritability, aggression, and apathy in Huntington and Alzheimer DiseaseThe Journal of Nervous and Mental Disease.alzheimer disease, J Nerv Ment Dis 178 (1), 1990, 20–26.

[10] J. Grace, J. Stout and P. Malloy, Assessing Frontal Lobe Behavioral Syndromes with the Frontal Lobe Personality Sfrontal lobe behavioral syndromes with the frontal lobe personality scale, Assessment .6 (3), 1999, 269–284.

[11] D. Kaufer, J. Cummings, P. Ketchel, V. Smith, A. MacMillan, T. Shelley, et al., Validation of the NPI-Q, a Brief Clinical Form of the Neuropsychiatric InventoryThe Journal of Neuropsychiatry and Clinical Neurosciences.brief clinical form of the neuropsychiatric inventory, J Neuropsychiatry Clin Neurosci 12 (2), 2000, 233–239.

[12] S. Chantoin, C. Hazif-Thomas, R. Billon and P. Thomas, Construction d’une échelle d’appréciation de la démotivation chez la personne âgée, L’Encéphale 27 (7), 2001, 450–458.

[13] P. Robert, S. Clairet, M. Benoit, J. Koutaich, C. Bertogliati, O. Tible, et al., The Apathy Inventory: assessment of apathy and awareness in Alzheimer’s disease, Parkinson’s disease and mild cognitive impairment, International Journal of Geriatric J Geriatr Psychiatry 17 (12), 2002, 1099–1105.

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[14] M.E. Strauss and S.D. Sperry, An informant-based assessment of apathy in Alzheimer disease, Neuropsychiatryneuropsychology, and behavioral neurology Neuropsychol Behav Neurol 15 (September (3)), 2002, 176–183.

[15] H. Belanger, L. Brown, T. Crowell, R. Vanderploeg and G. Curtiss, The Key Behaviors Change Inventory and Executive Functioning in an Elderly Clinic SampleThe Clinical Neuropsychologist (Neuropsychology, Development and Cognition: Section D)key behaviors change inventory and executive functioning in an elderly clinic sample, Clin Neuropsychol 16 (3), 2002, 251–257.

[16] P. Sockeel, K. Dujardin, D. Devos, C. Deneve, A. Destée and L. Defebvre, The Lille apathy rating scale (LARS), a new instrument for detecting and quantifying apathy: validation in Parkinson’s disease, Journal of Neurology, Neurosurgery & Psychiatry Neurol Neurosurg Psychiatr 77 (5), 2006, 579–584.

[17] K. Dujardin, P. Sockeel, A. Carette, M. Delliaux and L. Defebvre, Assessing apathy in everyday clinical practice with the short-form Lille Apathy Rating Scale, Movement Disorders. Disord 28 (14), 2013, 2014–2019.

[18] K. Dujardin, P. Sockeel, M. Delliaux, A. Destée and L. Defebvre, The Lille Apathy Rating Scale: Vlille apathy rating scale: validation of a caregiver-based version, Movement Disorders. Disord 23 (6), 2008, 845–849.

[19] K. De Medeiros, P. Robert, S. Gauthier, F. Stella, A. Politis, J. Leoutsakos, et al., The Neuropsychiatric Inventory-Clinician rating scale (NPI-C): reliability and validity of a revised assessment of neuropsychiatric symptoms in dementia, International Psychogeriatrics. Psychogeriatr 22 (06), 2010, 984–994.

[20] R. Leontjevas, A. Evers-Stephan, M. Smalbrugge, A. Pot, V. Thewissen, D. Gerritsen, et al., A comparative validation of the abbreviated apathy evaluation scale (AES-10) with the neuropsychiatric inventory apathy subscale against diagnostic criteria of apathy, J Am Med Dir Assoc 13 (3), 2012, 308.e1-308.e6.

[21] L. Agüera-Ortiz, N. Gil-Ruiz, I. Cruz-Orduña, et al., A novel rating scale for the measurement of apathy in institutionalized persons with dementia: The APADEM-NH, . The American Journal of Geriatric Psychiatry.Am J Geriatr Psychiatry 23 (2), 2015, 149–159.

[22a] R. Radakovic and S. Abrahams, Developing a new apathy measurement scale: Dimensional Apathy Scale, Psychiatry Res earch.219 (3), 2014, 658–663.

[22b] Radakovic, R., Stephenson, L., Colville, S., Swingler, R., Chandran, S., & Abrahams, S. (2016). Multidimensional apathy in ALS: validation of the Dimensional Apathy Scale. Journal of Neurology, Neurosurgery, and Psychiatry, 87, 663-669.

[23] Y. Ang, P. Lockwood, M. Apps, K. Muhammed and M. Husain, Distinct Subtypes of Apathy Revealed by the Apathy Motivation IndexPLOS ONE.subtypes of apathy revealed by the apathy motivation index, PLoS One 12 (1), 2017, e0169938.