OBJECTIVES: The goal of this research was to compare the effect of donepezil oral standard tablets (OST) versus donepezil oral disintegrating tablets (ODT) on stress and objective burden in caregivers of de novo patients with dementia of AD in routine medical practice.  METHODS: A 6-month, prospective, observational study enrolled naïve patients with possible/probable AD according to DSM-IV/NINCDS-ADRDA criteria. Comparison on caregiver stress and objective burden was carried-out between donepezil formulations of OST and ODT for a 6 month period. The self-administered ZARIT scale and daily hours devoted to the care of patients on basic and instrumental activities of daily-living (BADL, IADL), behaviour supervision and nursing home institutionalization were computed. RESULTS: 547 naïve and de novo AD patients were analyzed: 123 (22.5%) received OST and 424 (77.5%) ODT, at 7.1 (2.5) and 7.1 (2.6) mg/day, respectively. No significant differences were observed in age, sex distribution, schooling, educational training, or relationship with main caregiver between groups. Baseline clinical characteristics (comorbidities, symptoms of dementia duration, MMSE scoring) were homogeneous between groups and remained unchanged during the study; Adjusted ZARIT scoring was reduced significantly in ODT group by -1.1 point (p=0.001) but this was not statistically higher than the reduction observed in OST cohort; -0.5 (p=0.527 between groups comparison). Daily hours of care on BADL and IADL were not statistically different between cohorts and remained unchanged during the study. Also, average number of hours/day on behaviour supervision or general supervision and the percentage of caregivers having to quit their jobs were similar. CONCLUSIONS: Findings of this study show that both subjective and objective burden of caregivers of de novo patients with AD treated with donepezil remain stables during the 6-month period of the study, and it is unrelated with type of formulation given to patients.