Thirty-two severe AD patients (MMSE ?6) in N1 and N2 (16 vs. facility). The Vitality Index was used to assess daily activities and the introduction of rehabilitation. Results The response ratio (MMSE 3+) of donepezil was 37.5% in N2. The combination of donepezil with the psychosocial intervention improved the Vitality Index total score, and Communication, Eating, and Rehabilitation subscores (Wilcoxon, p =?0.016, 0.038, 0.023, and 0.011, respectively). Most of them were smoothly introduced to rehabilitation, and the proportion of accidental falls decreased. Psychosocial intervention in N1 without the drug only improved the total score (Wilcoxon, p =?0.046). Conclusions A combined therapeutic Estetrol approach of donepezil and psychosocial intervention can have a positive effect, even for severe patients through the introduction of rehabilitation and decreasing accidental falls. However, these findings require replication in a larger cohort. AD have consistently reported clinically positive effects. A combining effect with psychosocial intervention was reported in AD patients. We herein performed a combining approach for AD patients in LTCJFs, and found that a combined therapeutic approach of donepezil and psychosocial intervention can have a positive effect, through the introduction of rehabilitation and decreasing accidental falls. Effect of psychosocial intervention The results in Analysis 1 (N1) demonstrated that psychosocial intervention, including the RO and reminiscence approach, was effective in the absence of donepezil administration. However, the effect was considered to be weaker than that achieved in combination with the drug (Analysis 2 (N2)), since no significant differences were noted in the subscores. Clinically, we know that AD patients who manifest recent memory deficit can maintain intact remote memory, and that they can retain their skills. We considered the patients life history and designed a psychosocial intervention program that was aligned with the patients remote memories and skills. Good emotional relationships between the patients and staff, as shown by perfect participation rates, can enhance the positive effect of the intervention content. Effect of combined donepezil administration and psychosocial intervention The results in Analysis 2 (N2) revealed several things. The effects of donepezil on MMSE were not apparent unless the psychosocial intervention was added. This meant that the drug was considered to be ineffective according to the MMSE criteria for drug responders. This was probably due to the limitation of the dose of 10?mg/day of the drug, and while the use of 23?mg/day donepezil is anticipated, it is not yet permitted in Japan. However, when the psychosocial intervention was provided in combination with the drug, the MMSE-based response ratio was calculated as 37.5%. All patients receiving the combined drug and psychosocial interventions (IDs #9 through 16) were introduced smoothly for rehabilitation and one patient (ID #9) was discharged from N2 and returned to her home. Previous reports have indicated that the drug could stimulate attention through the frontal-parietal or basal ganglia networks [25-27]. The preservation of function of Estetrol the patients, even in the severe stage of AD, was suspected to be activated by psychosocial intervention, after stimulation of MPO the patients attention function by donepezil. The decreased rate of falling was also suspected to be due to such a Estetrol combined effect. These findings also suggest that psychosocial intervention could be considered to be an outcome of the donepezil treatment. The financial costs of combining of drug and psychosocial intervention might worry LTHCF managers. However, after an effective combining intervention, the ratio of discharge of the patients to their homes might increase like ID #9. This increased turnover Estetrol can obtain additional income by the LTCI. Limitation of the study In this study, we could examine Estetrol only two LTCHFs. Indeed, it is not easy to involve LTCHFs for research, especially for drug treatment, since it is directly connected to the matter of management. The N1 and N2 facilities have close relationships with our laboratory, and patients there have been able to undergo CT or MRI for the purpose of research. Therefore, we should cautious about the institution bias in interpreting the results. For statistical analyses, we did not perform a three-way design (Institute*drug*psychosocial intervention) due to the limited numbers of patients. Regarding the outcomes, we used the Vitality Index, an observational scale, which is affected by the skill of the observers. However, the Japanese.