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. The objective of this study was to investigate whether IGF-I is associated with cognitive performance and 3-year cognitive decline in 1318 subjects, aged 65-88 years. Cross-sectionally, IGF-I was directly related to information processing speed, memory, fluid intelligence, and Mini-Mental State Examination (MMSE) score, but these associations did not remain significant after adjustment for age and other factors. Analysis in quintiles of IGF-I revealed a threshold effect of low IGF-I on information processing speed, with lower speed in subjects in the lowest quintile of IGF-I (<9.4 nmol/l)(1) versus those in the other four quintiles (fully adjusted B=-0.89; 95% CI, -1.72 to -0.05). This threshold of low IGF-I was also observed for 3-year decline in information processing speed (adjusted RR=1.78; 95% CI, 1.19-2.68). In summary, this study suggests that IGF-I levels below 9.4 nmol/l are negatively associated with both the level and decline of information processing speed.