Donepezil May Reduce Insulin-Like Growth Factor-1 (IGF-1) Levels in Alzheimer’s disease

Objective: Determine if donepezil will raise the insulin-like growth factor-1 levels of patients with amnestic mild cognitive impairment and Alzheimer's disease. Design: In an outpatient setting, recruit amnestic mild cognitive impairment and Alzheimer's disease patients who were to start treatment with donepezil. Measure total serum insulin-like growth factor-1 levels before and after 3-6 months of treatment. Results: Twenty-four patients were recruited. After a mean duration of 129 ± 37 days, 14 patients returned taking 5 mg (n=4) or 10 mg (n=10) donepezil per day. Twelve patients experienced decreases in their insulin-like growth factor-1 levels, one had no change, and one experienced an increase. Their mean insulin-like growth factor-1 level dropped by 13%, from 113 ± 31 ng/ml to 98 ± 28 ng/ml (p<0.001). Conclusion: Contrary to the expected increase in insulin-like growth factor-1 levels in response to donepezil that has been reported for normal elderly adults, our patients experienced decreases. This finding suggests that the somatotropic axis is altered in amnestic mild cognitive impairment and Alzheimer's disease relative to normal older adults.