Agitation in Alzheimer's disease: Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria

Adelaide De Mauleon; Zahinoor Ismail; Paul Rosenberg; David Miller; Christelle Cantet; Cedric O'Gorman; Bruno Vellas; Constantine Lyketsos; Maria Soto

doi:10.1002/alz.12335

Agitation in Alzheimer's disease: Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria

Adelaide De Mauleon, Zahinoor Ismail, Paul Rosenberg, David Miller, Christelle Cantet, Cedric O'Gorman, Bruno Vellas, Constantine Lyketsos, Maria Soto

School of Medicine

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

Abstract

Introduction: The 2017 European Union-North American Clinical Trials in Alzheimer's Disease Task Force recommended development of clinician-rated primary outcome measures for Alzheimer's disease (AD) agitation trials, incorporating International Psychogeriatric Association (IPA) criteria. Methods: In a modified Delphi process, Cohen-Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory-Clinician (NPI-C) items were mapped to IPA agitation domains generating novel instruments, CMAI-IPA and NPI-C-IPA. Validation in the Agitation and Aggression AD Cohort (A3C) assessed minimal clinically important differences (MCIDs), change sensitivity, and predictive validity. Results: MCID was –17 (odds ratio [OR] = 14.9, 95% confidence interval [CI] = 6.8–32.6) for CMAI; –5 (OR = 9.3, 95% CI = 4.0–21.2) for CMAI-IPA; –3 (OR = 11.9, 95% CI = 4.1–34.8) for NPI-C-A+A; and –5 (OR = 7.8, 95% CI = 3.4–17.9) for NPI-C-IPA at 3 months. Areas under the curve suggested no scale better predicted global clinician ratings. Sensitivity to change for all measures was high. Conclusion: Internal consistency and reliability analyses demonstrated better accuracy for the NPI-C-IPA than for the CMAI-IPA and can be used for agitation clinical trial inclusion, and for response to intervention.

Original language	English (US)
Journal	Alzheimer's and Dementia
DOIs	https://doi.org/10.1002/alz.12335
State	Accepted/In press - 2021

Keywords

Alzheimer's disease
aggression
agitation
dementia
efficacy
gold standard
measure
neuropsychiatric symptoms
outcome
research
scales
trials
validation

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

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10.1002/alz.12335

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Agitation in Alzheimer's disease : Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria. / De Mauleon, Adelaide; Ismail, Zahinoor; Rosenberg, Paul; Miller, David; Cantet, Christelle; O'Gorman, Cedric; Vellas, Bruno; Lyketsos, Constantine; Soto, Maria.

In: Alzheimer's and Dementia, 2021.

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

@article{e5b136cd9fbe45f8ac4cd1a638d91abe,

title = "Agitation in Alzheimer's disease: Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria",

abstract = "Introduction: The 2017 European Union-North American Clinical Trials in Alzheimer's Disease Task Force recommended development of clinician-rated primary outcome measures for Alzheimer's disease (AD) agitation trials, incorporating International Psychogeriatric Association (IPA) criteria. Methods: In a modified Delphi process, Cohen-Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory-Clinician (NPI-C) items were mapped to IPA agitation domains generating novel instruments, CMAI-IPA and NPI-C-IPA. Validation in the Agitation and Aggression AD Cohort (A3C) assessed minimal clinically important differences (MCIDs), change sensitivity, and predictive validity. Results: MCID was –17 (odds ratio [OR] = 14.9, 95% confidence interval [CI] = 6.8–32.6) for CMAI; –5 (OR = 9.3, 95% CI = 4.0–21.2) for CMAI-IPA; –3 (OR = 11.9, 95% CI = 4.1–34.8) for NPI-C-A+A; and –5 (OR = 7.8, 95% CI = 3.4–17.9) for NPI-C-IPA at 3 months. Areas under the curve suggested no scale better predicted global clinician ratings. Sensitivity to change for all measures was high. Conclusion: Internal consistency and reliability analyses demonstrated better accuracy for the NPI-C-IPA than for the CMAI-IPA and can be used for agitation clinical trial inclusion, and for response to intervention.",

keywords = "Alzheimer's disease, aggression, agitation, dementia, efficacy, gold standard, measure, neuropsychiatric symptoms, outcome, research, scales, trials, validation",

author = "{De Mauleon}, Adelaide and Zahinoor Ismail and Paul Rosenberg and David Miller and Christelle Cantet and Cedric O'Gorman and Bruno Vellas and Constantine Lyketsos and Maria Soto",

note = "Funding Information: This work was supported in part by Ethypharm, by grant P30AG066507 to the Johns Hopkins Alzheimer's Disease Research Center, the Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease at Johns Hopkins University, and grants R01AG050515 and R01AG054771 to Dr. Rosenberg. Funding Information: David Miller is a full‐time employee of Signant Health. Cedric O'Gorman is a full‐time employee of Axsome Therapeutics. Constantine Lyketsos declares: (1) grant support (research or CME) from NIH, Functional Neuromodulation, Bright Focus Foundation and (2) payment as consultant or advisor from Avanir, Astellas, Roche, Karuna, SVB Leerink, Maplight, Axsome, Global Institute on Addictions. Maria Soto declares: payment as consultant or advisor from Avanir, Acadia. Zahinoor Ismail declares: (1) payment as consultant or advisor from Lundbeck/Otuska outside the submitted work; (2) payment to his institution from Acadia, Biogen, Roche, and Sunovion outside the submitted work. No conflicts are declared for the other authors. Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association",

year = "2021",

doi = "10.1002/alz.12335",

language = "English (US)",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Agitation in Alzheimer's disease

T2 - Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria

AU - De Mauleon, Adelaide

AU - Ismail, Zahinoor

AU - Rosenberg, Paul

AU - Miller, David

AU - Cantet, Christelle

AU - O'Gorman, Cedric

AU - Vellas, Bruno

AU - Lyketsos, Constantine

AU - Soto, Maria

N1 - Funding Information: This work was supported in part by Ethypharm, by grant P30AG066507 to the Johns Hopkins Alzheimer's Disease Research Center, the Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease at Johns Hopkins University, and grants R01AG050515 and R01AG054771 to Dr. Rosenberg. Funding Information: David Miller is a full‐time employee of Signant Health. Cedric O'Gorman is a full‐time employee of Axsome Therapeutics. Constantine Lyketsos declares: (1) grant support (research or CME) from NIH, Functional Neuromodulation, Bright Focus Foundation and (2) payment as consultant or advisor from Avanir, Astellas, Roche, Karuna, SVB Leerink, Maplight, Axsome, Global Institute on Addictions. Maria Soto declares: payment as consultant or advisor from Avanir, Acadia. Zahinoor Ismail declares: (1) payment as consultant or advisor from Lundbeck/Otuska outside the submitted work; (2) payment to his institution from Acadia, Biogen, Roche, and Sunovion outside the submitted work. No conflicts are declared for the other authors. Publisher Copyright: © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association

PY - 2021

Y1 - 2021

N2 - Introduction: The 2017 European Union-North American Clinical Trials in Alzheimer's Disease Task Force recommended development of clinician-rated primary outcome measures for Alzheimer's disease (AD) agitation trials, incorporating International Psychogeriatric Association (IPA) criteria. Methods: In a modified Delphi process, Cohen-Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory-Clinician (NPI-C) items were mapped to IPA agitation domains generating novel instruments, CMAI-IPA and NPI-C-IPA. Validation in the Agitation and Aggression AD Cohort (A3C) assessed minimal clinically important differences (MCIDs), change sensitivity, and predictive validity. Results: MCID was –17 (odds ratio [OR] = 14.9, 95% confidence interval [CI] = 6.8–32.6) for CMAI; –5 (OR = 9.3, 95% CI = 4.0–21.2) for CMAI-IPA; –3 (OR = 11.9, 95% CI = 4.1–34.8) for NPI-C-A+A; and –5 (OR = 7.8, 95% CI = 3.4–17.9) for NPI-C-IPA at 3 months. Areas under the curve suggested no scale better predicted global clinician ratings. Sensitivity to change for all measures was high. Conclusion: Internal consistency and reliability analyses demonstrated better accuracy for the NPI-C-IPA than for the CMAI-IPA and can be used for agitation clinical trial inclusion, and for response to intervention.

AB - Introduction: The 2017 European Union-North American Clinical Trials in Alzheimer's Disease Task Force recommended development of clinician-rated primary outcome measures for Alzheimer's disease (AD) agitation trials, incorporating International Psychogeriatric Association (IPA) criteria. Methods: In a modified Delphi process, Cohen-Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory-Clinician (NPI-C) items were mapped to IPA agitation domains generating novel instruments, CMAI-IPA and NPI-C-IPA. Validation in the Agitation and Aggression AD Cohort (A3C) assessed minimal clinically important differences (MCIDs), change sensitivity, and predictive validity. Results: MCID was –17 (odds ratio [OR] = 14.9, 95% confidence interval [CI] = 6.8–32.6) for CMAI; –5 (OR = 9.3, 95% CI = 4.0–21.2) for CMAI-IPA; –3 (OR = 11.9, 95% CI = 4.1–34.8) for NPI-C-A+A; and –5 (OR = 7.8, 95% CI = 3.4–17.9) for NPI-C-IPA at 3 months. Areas under the curve suggested no scale better predicted global clinician ratings. Sensitivity to change for all measures was high. Conclusion: Internal consistency and reliability analyses demonstrated better accuracy for the NPI-C-IPA than for the CMAI-IPA and can be used for agitation clinical trial inclusion, and for response to intervention.

KW - Alzheimer's disease

KW - aggression

KW - agitation

KW - dementia

KW - efficacy

KW - gold standard

KW - measure

KW - neuropsychiatric symptoms

KW - outcome

KW - research

KW - scales

KW - trials

KW - validation

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UR - http://www.scopus.com/inward/citedby.url?scp=85108000548&partnerID=8YFLogxK

U2 - 10.1002/alz.12335

DO - 10.1002/alz.12335

M3 - Article

C2 - 34132461

AN - SCOPUS:85108000548

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

ER -

Agitation in Alzheimer's disease: Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria

Abstract

Keywords

ASJC Scopus subject areas

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