title: Preliminary use of insulin-like growth factor-I as a biomarker for sorting high-dose donepezil responders among Japanese patients with Alzheimer's disease.
abstract: 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-I<or=99 ng/mL and MMSE<or=18, group B (n=9) had IGF-I<or=99 ng/mL and MMSE>18, 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.
authors.affiliation: Department of Neuropsychiatry, Showa University School of Medicine, Tokyo 157-8577, Japan. yamagata@fa3.so-net.ne.jp
authors.forename: Bun
authors.initials: B
authors.lastname: Yamagata
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroi
authors.initials: H
authors.lastname: Tomioka
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D044466:Asian People; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000378:metabolism; D007564:Japan; D008297:Male; D010880:Piperidines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D007189:Indans; D010880:Piperidines; D007334:Insulin-Like Growth Factor I; D000077265:Donepezil