ORIGINAL ARTICLE: Investigation of responders and non‐responders to long‐term donepezil treatment

Background: Donepezil is effective in maintaining the cognitive function of patients with mild to moderate Alzheimer's disease (AD). However, not all patients respond to donepezil. In the present study, we examined the clinical features of responders and non‐responders to long‐term donepezil treatment. Methods: The present retrospective study was performed on 95 AD outpatients who had been taking donepezil for ≥2 years. All subjects underwent periodic examinations of cognitive function, namely Mini‐Mental State Examination (MMSE) and Rorschach Cognitive Index (RCI), as well as clinical evaluations using the Clinical Dementia Rating (CDR) scale. Patients were divided into three groups as follows: (i) the ‘maintained’ group (MG), in which the global CDR score was maintained over the ≥2 years of treatment; (ii) the ‘declined’ group (DeG), in which the global CDR score increased one rank over the treatment period; and (iii) the ‘obvious and rapid decline’ group (ORDeG), in which the global CDR score increased two ranks early during the treatment period. Clinical features, treatment outcome, the time lag between a caregiver's recognition of the onset of dementia and the start of treatment, behavioral and psychological symptoms of dementia (BPSD), and cognitive functions were compared between the three groups. Results: Patients in the ORDeG (i.e. non‐responders) were significantly younger and had a longer time lag between the onset of dementia and the start of treatment than patients in the MG (P < 0.05). Of note, patients in the ORDeG had a longer period of executive dysfunction before treatment started than patients in the MG (P < 0.001). Evaluation of cognitive function revealed that mean changes from baseline on the MMSE and RCI were significantly lower for patients in the ORDeG compared with the MG at 8 and 4 months, respectively (P < 0.001 and P < 0.05, respectively). Conclusion: Donezepil non‐responders are likely to be younger and to have a longer time lag between the onset of dementia and the start of treatment, in particular a longer duration of executive dysfunction. Furthermore, the non‐responders do not demonstrate maintenance of cognitive functions in the short term. Thus, the early diagnosis of dementia and prompt initiation of donepezil treatment is indicated for a good outcome. To this end, it is important to educate people to recognize a deterioration of executive function in daily living.