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. 2025 Jun;37(3):100056.
doi: 10.1016/j.inpsyc.2025.100056. Epub 2025 Mar 18.

Cohen-mansfield agitation inventory total score as a measure of agitation and aggression in Alzheimer's disease: A factor analysis

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Free article

Cohen-mansfield agitation inventory total score as a measure of agitation and aggression in Alzheimer's disease: A factor analysis

Suzanne B Hendrix et al. Int Psychogeriatr. 2025 Jun.
Free article

Abstract

Background: Alzheimer's disease (AD) is often associated with agitation and aggression, which may impair function, impede care, and be a major source of stress for caregivers. The Cohen-Mansfield Agitation Inventory (CMAI) is often used to assess agitation and aggression. In its original, nursing-home version, it is a 29-item, caregiver-informed, clinician-administered 7-point scale that assesses the frequency of various agitation or aggressive behaviors. However, the instruction manual advises against the use of the total score in favor of a domain-based analysis. This recommendation has been followed in both clinical trials and practice. Because the CMAI is comprehensive and easy to administer, we sought to determine the validity of its total score as a single construct for assessing agitation and aggression in patients with AD.

Methods: We used a previously conducted factor analysis of the CMAI scores from two risperidone trials in patients with dementia (N = 648), and a follow-up analysis of the subset of patients with psychosis of AD (N = 479), to examine, using vector analysis and an effect-size-versus-signal-to-noise ratio analysis, whether the total CMAI score could confidently be used as a global measure of agitation and aggression in AD.

Results: Our findings suggest that the CMAI items from the dataset analyzed load into 4 clusters, which cover about 50 % of the total data variance. Surprisingly, items with the lowest signal-to-noise ratio (hitting, performing repetitious mannerisms, aimless pacing or wandering) had the strongest response to treatment (and vice versa), and belonged to different factors. The further observation that many items were spread among the factors, instead of primarily measuring a single factor or domain, suggests that there is a continuum of symptoms, and separating them into domains requires separating very similar items that measure two or more domains.

Conclusions: These findings suggest that assessing agitation and aggression via CMAI domains instead of the total score is likely to miss important behavioral signals. Using total CMAI score in clinical trials and practice, along with the assessment of individual items, is warranted.

Keywords: Agitation and aggression; Alzheimer’s disease; Clinical outcome assessment; Cohen-Mansfield Agitation Inventory (CMAI).

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Conflict of interest statement

Declaration of Competing Interest SBH is the CEO and owner of Pentara Corporation, which provides statistical consulting and clinical data management services to pharmaceutical companies, especially in neurodegenerative disease areas. PBR has received research grants from the National Institutes of Aging, Alzheimer's Clinical Trials Consortium, Richman Family Precision Medicine Center of Excellence on Alzheimer’s Disease, Eisai, Functional Neuromodulation, and Lilly; honoraria from Lilly, GLG, Leerink, Cerevel, Cerevance, Bioxcel, Sunovion, Acadia, Medalink, Novo Nordisk, Noble Insights, TwoLabs, Otsuka, Lundbeck, Acadia, MedaCorp, ExpertConnect, HMP Global, Sinaptica, Synaptogenix, Worldwide Clinical Trials, and Neurology Week. PBR has received grant support from National Institute on Aging included AGRO1054771 (CRD), AGRO1050515 (dronabinol), and AGRO1046543 (ADMET II). JLC has provided consultation to Acadia, Acumen, ALZpath, Annovis, Aprinoia, Artery, Biogen, Biohaven, BioXcel, Bristol-Myers Squib, Eisai, Fosun, GAP Foundation, Green Valley, Janssen, Karuna, Kinoxis, Lighthouse, Lilly, Lundbeck, LSP/eqt, Mangrove Therapeutics, Merck, MoCA Cognition, New Amsterdam, Novo Nordisk, Optoceutics, Otsuka, Oxford Brain Diagnostics, Praxis, Prothena, ReMYND, Roche, Scottish Brain Sciences, Signant Health, Simcere, sinaptica, T-Neuro, TrueBinding, and Vaxxinity pharmaceutical, assessment, and investment companies. CKL has received grant supports from NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Functional Neuromodulation, Bright Focus Foundation. CKL has provided consultations 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, Zinfandel, BMS, Abvie, Janssen, Orion, Servier, Astellas, SVB Leerink, Roche, Avanir, Karuna, Maplight, Axsome, GIA, GW Research Limited, Merck, EXCIVA GmbH, Otsuka, IntraCellular Therapies, Medesis, Karuna, BMS, and Abbvie. Dr. Porsteinsson reports personal fees from Acadia Pharmaceuticals, Athira, Axsome, Biogen, BMS, Cognitive Research Corp, Eisai, IQVIA, Lundbeck, Novartis, ONO Pharmaceuticals, Otsuka, WCG, WebMD, and Xenon; grants to his institution from Alector, Athira, Biogen, Cassava, Eisai, Eli Lilly, Genentech/Roche, Vaccinex, NIA, NIMH, and DOD. He is a member of the Scientific Advisory Board of Alzheon, Athira, and Cognition Therapeutics. MS is consulting for Eisai, NovoNordisk, Otsuka Lundbeck. BLB and DH reports no industry consulting or fees.

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