Objectives: To examine the association between caregiver (CG) depression and increase in elder mistreatment and to investigate whether change in care recipient (CR) neuropsychiatric symptoms (NPS) and change in CG-perceived burden influence this association. Methods: Using 2-year longitudinal data, we analyzed a consecutive sample of 800 Chinese primary family CGs and their CRs with mild cognitive impairment or mild-to-moderate dementia recruited from the geriatric and neurological departments of 3 Grade-A hospitals in the People's Republic of China. Participatory dyads were assessed between September 2015 and February 2016 and followed for 2 years. Results: CG depression at baseline was associated with a sharper increase in psychological abuse and neglect. For CRs with increased NPS, having a depressed CG predicted a higher level of psychological abuse than for those CRs without NPS. For CGs with decreased burden, the level of depression was associated with a slower increase in neglect than for CGs who remained low burden. Discussion: This study showed the differential impact of CG depression on the increase in elder mistreatment depending on the change in CR NPS and CG-perceived burden. Conclusions: The present findings provide valuable insights into the design of a systematic and integrative intervention protocol for elder mistreatment that simultaneously focuses on treating CG depression and perceived burden and CR NPS.