Use of serum insulin-like growth factor-I levels to predict psychiatric non-response to donepezil in patients with Alzheimer's disease.
OBJECTIVE
Insulin-like growth factor-I (IGF-I) deficiency may be involved in cognitive deficits seen with aging and in neurodegenerative diseases such as Alzheimer's disease (AD). This study was aimed at investigating whether non-responder to donepezil could be predicted using decreased serum levels of IGF-I in AD patients.


METHODS
This study involved 106 elderly subjects: 50 patients with AD and 56 age-matched controls without dementia. In patients with AD, donepezil was given orally 3 mg/day for 4 weeks and 5 mg/day for another 12 weeks. AD patients were divided into responders and non-responders based on the changes in mini-mental state examination (MMSE) scores before and 16 weeks after treatment with donepezil. Serum levels of IGF-I and atherogenic biomarkers were determined.


RESULTS
Before treatment with donepezil, there was a significant positive correlation between serum IGF-I levels and the MMSE scores in all subjects. Serum IGF-I levels and the MMSE scores were significantly lower in AD patients than in non-demented controls and were the lowest in non-responders to donepezil. Atherogenic biomarkers (LDL cholesterol, triglycerides, lipoprotein(a), lipid peroxide, apolipoprotein E, and glucose levels) did not differ significantly among these groups. On multiple logistic regression, non-responders to donepezil showed decreased serum IGF-I levels <110 ng/ml and MMSE scores <15 points before treatment.


CONCLUSIONS
These findings suggest that decreased levels of serum IGF-I combined with MMSE scores before treatment could predict non-responders to donepezil among AD patients, which may be a simple and practical method for selecting patients expected to show a response to treatment.
Tei
Eitetsu
E
Department of Neuropsychiatry, Showa University School of Medicine, Tokyo, Japan.
Yamamoto
Hideki
H
Watanabe
Takuya
T
Miyazaki
Akira
A
Nakadate
Toshio
T
Kato
Nobumasa
N
Mimura
Masaru
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D007334:Insulin-Like Growth Factor I; D000077265:Donepezil