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.

Validating the Mild Behavioral Impairment Checklist in a Cognitive Clinic: Comparisons With the Neuropsychiatric Inventory Questionnaire

“…25 Future studies focusing on impulse dyscontrol as a predictor of incident cognitive decline and dementia would further elucidate the role of this domain, and its relationship to the presence and measurement of syndromic agitation in dementia. 61,62 Social inappropriateness describes not following societal norms and lacking social graces, tact, and empathy. 24 Social inappropriateness as measured by the MBI-C was significantly associated with lower MoCA score (β À.33; 95% CI À.59, À.08).…”

“… 25 Future studies focusing on impulse dyscontrol as a predictor of incident cognitive decline and dementia would further elucidate the role of this domain, and its relationship to the presence and measurement of syndromic agitation in dementia. 61 , 62 …”

Agitation in cognitive disorders: Progress in the International Psychogeriatric Association consensus clinical and research definition

“…All items from the CMAI were included, as were all items from the agitation, aggression, aberrant motor activity, abnormal vocalizations, disinhibition, and irritability/lability domains of the NPI-C. Through an iterative process described elsewhere (de Mauleon et al , 2021), two sub-scales were described, which could be abstracted from the CMAI, (the 19-item CMAI-IPA) and the NPI-C (the 25-item NPI-C-IPA). Performance was then assessed in 262 participants in the French Agitation and Aggression AD Cohort (A3C) cohort (De Mauleon et al , 2021), a 12-month longitudinal prospective observational cohort of memory clinic and long-term care patients designed to simulate a clinical trial.…”

“…Performance was then assessed in 262 participants in the French Agitation and Aggression AD Cohort (A3C) cohort (De Mauleon et al , 2021), a 12-month longitudinal prospective observational cohort of memory clinic and long-term care patients designed to simulate a clinical trial. Abstracted measures were compared to each original scale for performance characteristics including minimally clinically important difference (MCID), sensitivity, specificity, area under the curve (AUC), sensitivity to change, test-retest reliability, accuracy, and predictive validity (de Mauleon et al , 2021). Globally, all measures were reasonably similar, and all were internally valid.…”

“…Also, as a frequency measure without a severity component, the CMAI may not have fully captured change while both frequency and severity are captured in the clinician ratings in the NPI-C. With respect to domains of motor activity, verbal aggression, and physical aggression, internal consistency of the NPI-C-IPA was good, but for the CMAI Cronbach’s alpha was low for verbal aggression and very low for physical aggression. Overall, the authors concluded that internal consistency and reliability analyses demonstrated better accuracy for NPI-C-IPA compared to CMAI-IPA, with NPI-C-IPA also being more clinically relevant (de Mauleon et al , 2021). The domain analyses address a remaining controversy within the agitation definition concerning the clustering of these behaviors and this report reinforces the need for further research on this topic.…”