Diagnostic criteria for apathy in neurocognitive disorders

David S Miller¹, Philippe Robert^{2

3

4}, Larry Ereshefsky⁵, Lawrence Adler⁶, Daniel Bateman⁷, Jeff Cummings^{8

9}, Steven T DeKosky¹⁰, Corinne E Fischer^{11

12}, Masud Husain^{13

14

15}, Zahinoor Ismail¹⁶, Judith Jaeger¹⁷, Alan J Lerner¹⁸, Abby Li¹⁹, Constantine G Lyketsos²⁰, Valeria Manera^{2

3}, Jacobo Mintzer²¹, Hans J Moebius²², Moyra Mortby²³, Didier Meulien²⁴, Stephane Pollentier²⁵, Anton Porsteinsson²⁶, Jill Rasmussen²⁷, Paul B Rosenberg²⁰, Myuri T Ruthirakuhan¹⁹, Mary Sano²⁸, Carla Zucchero Sarracini¹⁹, Krista L Lanctôt^{19

29}

Affiliations

¹ Signant Health, Blue Bell, Pennsylvania, USA.
² Cognition Behaviour Technology Lab, Université Côte d'Azur, Nice, France.
³ Association Innovation Alzheimer, Nice, France.
⁴ Centre Memoire, Centre Hospitalier Universitaire de Nice, Nice, France.
⁵ Follow the Molecule, Marina del Rey, California, USA.
⁶ Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁷ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁸ Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Nevada, USA.
⁹ Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada, USA.
¹⁰ Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
¹¹ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
¹² Keenan Research Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
¹³ Department of Experimental Psychology, University of Oxford, Oxford, UK.
¹⁴ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
¹⁵ Oxford NIHR Biomedical Research Centre, Oxford, UK.
¹⁶ Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
¹⁷ CognitionMetrics, Wilmington, Delaware, USA.
¹⁸ University Hospitals - Case Western Reserve University, Cleveland, Ohio, USA.
¹⁹ Sunnybrook Research Institute, Toronto, Ontario, Canada.
²⁰ Johns Hopkins University, Baltimore, Maryland, USA.
²¹ Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina, USA.
²² Moebius-Consult, Baar, Switzerland.
²³ UNSW Ageing Futures Institute, The University of New South Wales, Sydney, Australia.
²⁴ Clinical Research and Development, H. Lundbeck A/S, Valby, Denmark.
²⁵ Boehringer Ingelheim Pharma GmbH & Co KG, CNS Diseases Research, Biberach an der Riss, Germany.
²⁶ University of Rochester, Rochester, New York, USA.
²⁷ Psi-Napse, Dorking, UK.
²⁸ Alzheimer Disease Research Center, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²⁹ Departments of Psychiatry and Pharmacology/Toxicology, University of Toronto, Toronto, Ontario, Canada.

PMID: 33949763
PMCID: PMC8835377
DOI: 10.1002/alz.12358

Diagnostic criteria for apathy in neurocognitive disorders

David S Miller et al. Alzheimers Dement. 2021 Dec.

. 2021 Dec;17(12):1892-1904.

doi: 10.1002/alz.12358. Epub 2021 May 5.

Authors

Affiliations

¹ Signant Health, Blue Bell, Pennsylvania, USA.
² Cognition Behaviour Technology Lab, Université Côte d'Azur, Nice, France.
³ Association Innovation Alzheimer, Nice, France.
⁴ Centre Memoire, Centre Hospitalier Universitaire de Nice, Nice, France.
⁵ Follow the Molecule, Marina del Rey, California, USA.
⁶ Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁷ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁸ Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Nevada, USA.
⁹ Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada, USA.
¹⁰ Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
¹¹ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
¹² Keenan Research Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
¹³ Department of Experimental Psychology, University of Oxford, Oxford, UK.
¹⁴ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
¹⁵ Oxford NIHR Biomedical Research Centre, Oxford, UK.
¹⁶ Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
¹⁷ CognitionMetrics, Wilmington, Delaware, USA.
¹⁸ University Hospitals - Case Western Reserve University, Cleveland, Ohio, USA.
¹⁹ Sunnybrook Research Institute, Toronto, Ontario, Canada.
²⁰ Johns Hopkins University, Baltimore, Maryland, USA.
²¹ Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina, USA.
²² Moebius-Consult, Baar, Switzerland.
²³ UNSW Ageing Futures Institute, The University of New South Wales, Sydney, Australia.
²⁴ Clinical Research and Development, H. Lundbeck A/S, Valby, Denmark.
²⁵ Boehringer Ingelheim Pharma GmbH & Co KG, CNS Diseases Research, Biberach an der Riss, Germany.
²⁶ University of Rochester, Rochester, New York, USA.
²⁷ Psi-Napse, Dorking, UK.
²⁸ Alzheimer Disease Research Center, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²⁹ Departments of Psychiatry and Pharmacology/Toxicology, University of Toronto, Toronto, Ontario, Canada.

PMID: 33949763
PMCID: PMC8835377
DOI: 10.1002/alz.12358

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.

Keywords: apathy; behavior; cognition; diagnostic criteria; emotion; motivation; neurocognitive disorder (NCD); neuropsychiatric symptoms (NPS).

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Conflict of interest statement

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 Up To Date, and is the Associate Editor for Neurotherapeutics. 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.

References

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Diagnostic criteria for apathy in neurocognitive disorders

Affiliations

Diagnostic criteria for apathy in neurocognitive disorders

Authors

Affiliations

Abstract

Conflict of interest statement

References

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LinkOut - more resources

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