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Purpose: To explore the association between apathy and health-related quality of life (HRQoL) from resident and proxy perspectives and whether cognition and depression moderate this relationship.Methods: Secondary analyses with baseline data from a cluster randomized trial on the effects of a care program for depression in Nursing Homes (NHs) were conducted. For HRQoL, the Visual Analogue Scale (VAS) and the Dutch version of the European Quality of Life (EQ-5D) were administered to 521 NH residents, and to professional caregivers reporting from the perspective of the NH resident (Resident-Proxy) and from their own perspective (Proxy-Proxy). Utility scores (U) were calculated for the three perspectives. Apathy, depression, and cognition were measured using the 10-item Apathy Evaluation Scale, the Cornell Scale for Depression in Dementia, and the standardized Mini-Mental State Examination, respectively.Results: Mixed models adjusted for clustering within NH units revealed that apathy was negatively associated with HRQoL both from the Resident-Proxy perspective (EQ-5D VAS: estimated effect, - 0.31, P < 0.001; EQ-5D Utility: - 0.30, P < 0.001) and from the Proxy-Proxy perspective (VAS: - 0.29, P < 0.001; U: - 0.03, P < 0.001), but not from the Resident-Resident perspective (VAS: - 0.05, P = 0.423; Utility: - 0.08, P = 0.161). Controlling for depression and cognition and their interaction terms with apathy did not change the results.Conclusion: Apathy is negatively associated with NH resident HRQoL as reported by proxies. Depression and cognitive functioning do not moderate this association. NH residents do not self-report a relationship between apathy and HRQoL. More research is needed to understand caregiver and NH resident attitudes and underlying assumptions regarding apathy and HRQoL. [ABSTRACT FROM AUTHOR]