Preliminary use of insulin-like growth factor-I as a biomarker for sorting high-dose donepezil responders among Japanese patients with Alzheimer's disease.

摘要

Treatment with donepezil (maximum dose, 10 mg/day) was recently approved in Japan for severe Alzheimer's disease (AD). We examined the usefulness of serum insulin-like growth factor-I (IGF-I) level as a biomarker for predicting responders to 10 mg/day-donepezil treatment among mild-to-moderate AD patients. The study population consisted of 23 mild-to-moderate AD patients, who were non-responders to 5 mg/day-donepezil treatment. AD patients were divided into responders and non-responders based on changes in mini-mental state examination (MMSE) scores before and 12 weeks after increasing donepezil dose from 5 to 10 mg/day. Before increasing donepezil dose, based on serum IGF-I levels and MMSE scores positively correlated with each other, AD patients were classified into three groups. Group A (n=6) had IGF-I18, and group C (n=8) had IGF-I>99 ng/mL and MMSE>18. Serum IGF-I levels were significantly lower in groups A and B than group C. After 10 mg/day-donepezil treatment, the mean MMSE improved significantly only in group A. The prevalence of responders to the treatment was markedly greater in group A than in groups B and C. These results suggested that decreased serum IGF-I level combined with low MMSE score may be a useful biomarker for predicting responders to 10 mg/day-donepezil treatment in mild-to-moderate AD patients exhibiting a poor response to 5 mg/day-donepezil treatment.