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

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.

Automated summary

This study developed clinician-rated primary outcome measures for AD agitation trials, incorporating IPA criteria. The validation results in the A3C cohort showed that NPI-C-IPA demonstrated better internal consistency and reliability than CMAI-IPA, making it a useful tool for agitation clinical trials and intervention response assessment.