Objective: To validate the Caregiver-Perceived Burden Questionnaire (CPBQ) and report its psychometric properties. Methods: The CPBQ was administered to caregivers of patients with moderate-to-severe AD in a double-blind randomized trial comparing extended-release memantine to placebo (n = 676). Measurement properties were analyzed using factor analysis, classical test theory, and Rasch analysis. Results: Two subscales were identified: the Caregivers’ Assessment of the Patient (CAP) and the Caregivers’ Assessment of Themselves (CAT). The reliability was .89 (CAP) and .83 (CAT). The CAP scores were significantly correlated (r > .3) with scores from the Severe Impairment Battery (SIB) and the Neuropsychiatric Inventory (NPI). The CAT scores were significantly correlated with NPI scores. The CAT discriminated among patients by clinician-rated severity and significantly differentiated between responders and nonresponders. Conclusion: The CPBQ appears to be a reliable, valid, and responsive measure that enables linking caregiver’s perceptions about burden and patient function in patients with moderate-to-severe AD.