Diagnostic criteria for apathy in neurocognitive disorders

David S. Miller; Philippe Robert; Larry Ereshefsky; Lawrence Adler; Daniel Bateman; Jeff Cummings; Steven T. DeKosky; Corinne E. Fischer; Masud Husain; Zahinoor Ismail; Judith Jaeger; Alan J. Lerner; Abby Li; Constantine G. Lyketsos; Valeria Manera; Jacobo Mintzer; Hans J. Moebius; Moyra Mortby; Didier Meulien; Stephane Pollentier; Anton Porsteinsson; Jill Rasmussen; Paul B. Rosenberg; Myuri T. Ruthirakuhan; Mary Sano; Carla Zucchero Sarracini; Krista L. Lanctôt

doi:10.1002/alz.12358

Diagnostic criteria for apathy in neurocognitive disorders

David S. Miller, Philippe Robert, Larry Ereshefsky, Lawrence Adler, Daniel Bateman, Jeff Cummings, Steven T. DeKosky, Corinne E. Fischer, Masud Husain, Zahinoor Ismail, Judith Jaeger, Alan J. Lerner, Abby Li, Constantine G. Lyketsos, Valeria Manera, Jacobo Mintzer, Hans J. Moebius, Moyra Mortby, Didier Meulien, Stephane PollentierAnton Porsteinsson, Jill Rasmussen, Paul B. Rosenberg, Myuri T. Ruthirakuhan, Mary Sano, Carla Zucchero Sarracini, Krista L. Lanctôt

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.

Original language	English
Pages (from-to)	1892-1904
Number of pages	13
Journal	Alzheimer's and Dementia
Volume	17
Issue number	12
DOIs	https://doi.org/10.1002/alz.12358
State	Published - Dec 2021

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10.1002/alz.12358

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Miller, D. S., Robert, P., Ereshefsky, L., Adler, L., Bateman, D., Cummings, J., DeKosky, S. T., Fischer, C. E., Husain, M., Ismail, Z., Jaeger, J., Lerner, A. J., Li, A., Lyketsos, C. G., Manera, V., Mintzer, J., Moebius, H. J., Mortby, M., Meulien, D., ... Lanctôt, K. L. (2021). Diagnostic criteria for apathy in neurocognitive disorders. Alzheimer's and Dementia, 17(12), 1892-1904. https://doi.org/10.1002/alz.12358

@article{cc6701d7021a4c628f3796882e6bc454,

title = "Diagnostic criteria for apathy in neurocognitive disorders",

abstract = "Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.",

author = "Miller, {David S.} and Philippe Robert and Larry Ereshefsky and Lawrence Adler and Daniel Bateman and Jeff Cummings and DeKosky, {Steven T.} and Fischer, {Corinne E.} and Masud Husain and Zahinoor Ismail and Judith Jaeger and Lerner, {Alan J.} and Abby Li and Lyketsos, {Constantine G.} and Valeria Manera and Jacobo Mintzer and Moebius, {Hans J.} and Moyra Mortby and Didier Meulien and Stephane Pollentier and Anton Porsteinsson and Jill Rasmussen and Rosenberg, {Paul B.} and Ruthirakuhan, {Myuri T.} and Mary Sano and {Zucchero Sarracini}, Carla and Lanct{\^o}t, {Krista L.}",

note = "Funding Information: Dr. Miller is a full‐time employee of Signant Health. Dr. Robert reports grants from French Alzheimer's Association, French research ministry ANR, European H20 20 programs, French National Solidarity council, University C{\^o}te d'azur Idex; and consulting fees from Lundbeck and Servier outside the submitted work. Dr. Ereshefsky receives support from APEX Innovative Services, which conducts research for most pharma, and performing site for NIDA, and through Follow the Molecule LLC receives consulting compensation from Biogen, Bioxcel, Neurocrine, Taisho, Atlas Investments, Athira, Intracellular, Cerevel, and Karuna. Dr. Adler has no relevant disclosures. Dr. Bateman reports no conflicts of interest or disclosures. Dr. Cummings has provided consultation to Acadia, Actinogen, AgeneBio, Alkahest, Alzheon, Annovis, Avanir, Axsome, Biogen, BioXcel, Cassava, Cerecin, Cerevel, Cortexyme, EIP Pharma, Eisai, Foresight, GemVax, Genentech, Green Valley, Grifols, Karuna, Merck, Novo Nordisk, Otsuka, Resverlogix, Roche, Samumed, Samus, Signant Health, Suven, Third Rock, and United Neuroscience pharmaceutical and assessment companies. Dr. Cummings has stock options in ADAMAS, AnnovisBio, MedAvante, and BiOasis. Dr. Cummings owns the copyright of the Neuropsychiatric Inventory. Dr Cummings is supported by Keep Memory Alive (KMA), NIGMS grant P20GM109025, NINDS grant U01NS093334, and NIA grant R01AG053798. Dr. DeKosky chairs the medical advisory boards for Acumen and Cognition Therapeutics the DSMB for Biogen, is the editor for , and is the Associate Editor for . Dr. Fischer receives grant funding from Brain Canada, Patient Centred Outcomes Research Trust‐Fund, St. Michaels Hospital Foundation, Hoffman LaRoche, and Vielight Inc, all outside the submitted work. Dr. Husain reports grants from the Wellcome Trust, NIHR Biomedical Research Centre Oxford, European Union; and consulting fees from Otsuka, outside the submitted work. Dr. Ismail has received research support from the Alzheimer Society of Calgary, Brain Canada, Canadian Consortium on Neurodegeneration in Aging, Canadian Institutes of Health Research, and consulting fees from Janssen, Lundbeck, and Otsuka, all outside the submitted work. Dr. Jaeger is the owner of CognitionMetrics, LLC, which over the past two years has held consulting contracts with Acadia, Aptinix, Biogen, Eisai, Harmony, INmune Bio, Iproteos, Ironwood, Jazz Pharma, Janssen, LuMind, Lundbeck, Otsuka, Ovid, Perception, and Syndesi. Dr. Lerner receives grant support from National Institute on Aging, ADDF, Global Alzheimer's Platform foundation, and the Elizabeth Severance Prentiss Foundation. Ms. Li reports no conflicts of interest. Dr. Lyketsos has received grant funding from NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo‐Smith‐Kline, Eisai, Pfizer, Astra‐Zeneca, Lilly, Ortho‐McNeil, Bristol‐Myers, Novartis, National Football League, Elan, Functional Neuromodulation, Bright Focus Foundation; has been a consultant or advisor to Astra‐Zeneca, Glaxo‐Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, NFL Players Association, NFL Benefits Office, Avanir, Zinfandel, BMS, AbbVie, Janssen, Orion, Otsuka, Servier, Astellas, Roche, Karuna, SVB Leerink, Maplight, Axsome; and has received honoraria or travel support from Pfizer, Forest, Glaxo‐Smith Kline, and Health Monitor. Dr. Manera has no conflicts of interests to disclose. Dr. Mintzer has received research support from the National Institute on Aging, Alzheimer's Disease Cooperative Study (ADCS), Alzheimer's Disease Trials Research Institute (ATRI), Alzheimer's Clinical Trials Consortium (ACTC), Eisai Pharmaceuticals, AgeneBio, TauRx, ACADIA, Novartis, and Biogen as well as consulting fees from Otsuka, ACADIA, and Avanir. Dr. Moebius receives consulting compensation from Exciva and Athira through moebius‐consult LLC, all outside the submitted work. Dr. Mortby is supported by the Australian National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) Dementia Research Development Fellowship (#1102028). Dr. Muelien is a full‐time employee of H. Lundbeck SAS. Dr. Pollentier is a full‐time employee of Boehringer Ingelheim International GmbH. Dr. Porsteinsson reports personal fees from Acadia Pharmaceuticals, Avanir, Cadent Therapeutics, Functional Neuromodulation, Syneos, and BioXcel; and grants to his institution from Avanir, Biogen, Biohaven, Eisai, Eli Lilly, Genentech/Roche, and Novartis. Dr. Rasmussen is an independent consultant to psi‐napse, is an advisor to the NHS (Academic Health Science Network Kent, Surrey, Sussex, Surrey Heartlands ICS), and receives funding for consultancy/advisory board/speaker's bureau from Acadia, Alz Soc, Andera Partners, Biogen, ConSynance, Merck, Nuricia, and Roche. Dr. Rosenberg has received research support from the National Institute on Aging, Alzheimer's Association, Lilly, Functional Neuromodulation (FNMI), Lilly, Alzheimer's Disease Cooperative Study (ADCS), Alzheimer's Disease Trials Research Institute (ATRI), Alzheimer's Clinical Trials Consortium (ACTC), as well as consulting fees from GLG, Leerink, Otsuka, Avanir, ITI, IQVIA, Food and Drug Administration, Cerevel, Bioxcel, and Sunovion, all outside the submitted work. Dr. Ruthirakuhan has received funding through a Canadian Institute of Heath Research postdoctoral fellowship. Dr. Sano reports no conflicts of interest. Ms. Zucchero Sarracini report no conflicts of interest. Dr. Lanct{\^o}t reports grants from Alzheimer's Association, Alzheimer Society of Canada, Alzheimer's Drug Discovery Foundation, Canadian Institutes of Health Research, National Institute on Aging; and consulting fees from Abide, BioXcel, Cerevel, Exciva, Highmark Interactive, ICG Pharma, Kondor Pharma, and Otsuka, outside the submitted work. Up To Date Neurotherapeutics Funding Information: The authors would like to thank the following individuals for their contributions to the process of developing these diagnostic criteria: Tiffany Farchione (FDA), Jean Kim (FDA), Nancy Dickinson (FDA), Javier Muniz (FDA), Mike Davis (FDA), Valentina Mantua (formerly EMA, now FDA), Bruce Cuthbert (NIMH), and Jovier Evans (NIMH). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association",

year = "2021",

month = dec,

doi = "10.1002/alz.12358",

language = "English",

volume = "17",

pages = "1892--1904",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley & Sons Inc.",

number = "12",

}

Miller, DS, Robert, P, Ereshefsky, L, Adler, L, Bateman, D, Cummings, J, DeKosky, ST, Fischer, CE, Husain, M, Ismail, Z, Jaeger, J, Lerner, AJ, Li, A, Lyketsos, CG, Manera, V, Mintzer, J, Moebius, HJ, Mortby, M, Meulien, D, Pollentier, S, Porsteinsson, A, Rasmussen, J, Rosenberg, PB, Ruthirakuhan, MT, Sano, M, Zucchero Sarracini, C & Lanctôt, KL 2021, 'Diagnostic criteria for apathy in neurocognitive disorders', Alzheimer's and Dementia, vol. 17, no. 12, pp. 1892-1904. https://doi.org/10.1002/alz.12358

TY - JOUR

T1 - Diagnostic criteria for apathy in neurocognitive disorders

AU - Miller, David S.

AU - Robert, Philippe

AU - Ereshefsky, Larry

AU - Adler, Lawrence

AU - Bateman, Daniel

AU - Cummings, Jeff

AU - DeKosky, Steven T.

AU - Fischer, Corinne E.

AU - Husain, Masud

AU - Ismail, Zahinoor

AU - Jaeger, Judith

AU - Lerner, Alan J.

AU - Li, Abby

AU - Lyketsos, Constantine G.

AU - Manera, Valeria

AU - Mintzer, Jacobo

AU - Moebius, Hans J.

AU - Mortby, Moyra

AU - Meulien, Didier

AU - Pollentier, Stephane

AU - Porsteinsson, Anton

AU - Rasmussen, Jill

AU - Rosenberg, Paul B.

AU - Ruthirakuhan, Myuri T.

AU - Sano, Mary

AU - Zucchero Sarracini, Carla

AU - Lanctôt, Krista L.

N1 - Funding Information: Dr. Miller is a full‐time employee of Signant Health. Dr. Robert reports grants from French Alzheimer's Association, French research ministry ANR, European H20 20 programs, French National Solidarity council, University Côte d'azur Idex; and consulting fees from Lundbeck and Servier outside the submitted work. Dr. Ereshefsky receives support from APEX Innovative Services, which conducts research for most pharma, and performing site for NIDA, and through Follow the Molecule LLC receives consulting compensation from Biogen, Bioxcel, Neurocrine, Taisho, Atlas Investments, Athira, Intracellular, Cerevel, and Karuna. Dr. Adler has no relevant disclosures. Dr. Bateman reports no conflicts of interest or disclosures. Dr. Cummings has provided consultation to Acadia, Actinogen, AgeneBio, Alkahest, Alzheon, Annovis, Avanir, Axsome, Biogen, BioXcel, Cassava, Cerecin, Cerevel, Cortexyme, EIP Pharma, Eisai, Foresight, GemVax, Genentech, Green Valley, Grifols, Karuna, Merck, Novo Nordisk, Otsuka, Resverlogix, Roche, Samumed, Samus, Signant Health, Suven, Third Rock, and United Neuroscience pharmaceutical and assessment companies. Dr. Cummings has stock options in ADAMAS, AnnovisBio, MedAvante, and BiOasis. Dr. Cummings owns the copyright of the Neuropsychiatric Inventory. Dr Cummings is supported by Keep Memory Alive (KMA), NIGMS grant P20GM109025, NINDS grant U01NS093334, and NIA grant R01AG053798. Dr. DeKosky chairs the medical advisory boards for Acumen and Cognition Therapeutics the DSMB for Biogen, is the editor for , and is the Associate Editor for . Dr. Fischer receives grant funding from Brain Canada, Patient Centred Outcomes Research Trust‐Fund, St. Michaels Hospital Foundation, Hoffman LaRoche, and Vielight Inc, all outside the submitted work. Dr. Husain reports grants from the Wellcome Trust, NIHR Biomedical Research Centre Oxford, European Union; and consulting fees from Otsuka, outside the submitted work. Dr. Ismail has received research support from the Alzheimer Society of Calgary, Brain Canada, Canadian Consortium on Neurodegeneration in Aging, Canadian Institutes of Health Research, and consulting fees from Janssen, Lundbeck, and Otsuka, all outside the submitted work. Dr. Jaeger is the owner of CognitionMetrics, LLC, which over the past two years has held consulting contracts with Acadia, Aptinix, Biogen, Eisai, Harmony, INmune Bio, Iproteos, Ironwood, Jazz Pharma, Janssen, LuMind, Lundbeck, Otsuka, Ovid, Perception, and Syndesi. Dr. Lerner receives grant support from National Institute on Aging, ADDF, Global Alzheimer's Platform foundation, and the Elizabeth Severance Prentiss Foundation. Ms. Li reports no conflicts of interest. Dr. Lyketsos has received grant funding from NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo‐Smith‐Kline, Eisai, Pfizer, Astra‐Zeneca, Lilly, Ortho‐McNeil, Bristol‐Myers, Novartis, National Football League, Elan, Functional Neuromodulation, Bright Focus Foundation; has been a consultant or advisor to Astra‐Zeneca, Glaxo‐Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, NFL Players Association, NFL Benefits Office, Avanir, Zinfandel, BMS, AbbVie, Janssen, Orion, Otsuka, Servier, Astellas, Roche, Karuna, SVB Leerink, Maplight, Axsome; and has received honoraria or travel support from Pfizer, Forest, Glaxo‐Smith Kline, and Health Monitor. Dr. Manera has no conflicts of interests to disclose. Dr. Mintzer has received research support from the National Institute on Aging, Alzheimer's Disease Cooperative Study (ADCS), Alzheimer's Disease Trials Research Institute (ATRI), Alzheimer's Clinical Trials Consortium (ACTC), Eisai Pharmaceuticals, AgeneBio, TauRx, ACADIA, Novartis, and Biogen as well as consulting fees from Otsuka, ACADIA, and Avanir. Dr. Moebius receives consulting compensation from Exciva and Athira through moebius‐consult LLC, all outside the submitted work. Dr. Mortby is supported by the Australian National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) Dementia Research Development Fellowship (#1102028). Dr. Muelien is a full‐time employee of H. Lundbeck SAS. Dr. Pollentier is a full‐time employee of Boehringer Ingelheim International GmbH. Dr. Porsteinsson reports personal fees from Acadia Pharmaceuticals, Avanir, Cadent Therapeutics, Functional Neuromodulation, Syneos, and BioXcel; and grants to his institution from Avanir, Biogen, Biohaven, Eisai, Eli Lilly, Genentech/Roche, and Novartis. Dr. Rasmussen is an independent consultant to psi‐napse, is an advisor to the NHS (Academic Health Science Network Kent, Surrey, Sussex, Surrey Heartlands ICS), and receives funding for consultancy/advisory board/speaker's bureau from Acadia, Alz Soc, Andera Partners, Biogen, ConSynance, Merck, Nuricia, and Roche. Dr. Rosenberg has received research support from the National Institute on Aging, Alzheimer's Association, Lilly, Functional Neuromodulation (FNMI), Lilly, Alzheimer's Disease Cooperative Study (ADCS), Alzheimer's Disease Trials Research Institute (ATRI), Alzheimer's Clinical Trials Consortium (ACTC), as well as consulting fees from GLG, Leerink, Otsuka, Avanir, ITI, IQVIA, Food and Drug Administration, Cerevel, Bioxcel, and Sunovion, all outside the submitted work. Dr. Ruthirakuhan has received funding through a Canadian Institute of Heath Research postdoctoral fellowship. Dr. Sano reports no conflicts of interest. Ms. Zucchero Sarracini report no conflicts of interest. Dr. Lanctôt reports grants from Alzheimer's Association, Alzheimer Society of Canada, Alzheimer's Drug Discovery Foundation, Canadian Institutes of Health Research, National Institute on Aging; and consulting fees from Abide, BioXcel, Cerevel, Exciva, Highmark Interactive, ICG Pharma, Kondor Pharma, and Otsuka, outside the submitted work. Up To Date Neurotherapeutics Funding Information: The authors would like to thank the following individuals for their contributions to the process of developing these diagnostic criteria: Tiffany Farchione (FDA), Jean Kim (FDA), Nancy Dickinson (FDA), Javier Muniz (FDA), Mike Davis (FDA), Valentina Mantua (formerly EMA, now FDA), Bruce Cuthbert (NIMH), and Jovier Evans (NIMH). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association

PY - 2021/12

Y1 - 2021/12

N2 - Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.

AB - Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.

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U2 - 10.1002/alz.12358

DO - 10.1002/alz.12358

M3 - Article

C2 - 33949763

AN - SCOPUS:85105082946

SN - 1552-5260

VL - 17

SP - 1892

EP - 1904

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 12

ER -

Diagnostic criteria for apathy in neurocognitive disorders

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