Midlife Plasma Insulin-Like Growth Factor I and Cognitive Function in Older Men

Context: Emerging biological and epidemiological evidence suggests possible benefits of higher IGF-I levels in cognitive aging. Objective: The objective of the study was to examine the relation of midlife plasma IGF-I levels to late-life cognition. Design, Setting, and Participants: We conducted a secondary analysis from the Physicians’ Health Study II, a prospective cohort of U.S. male physicians. Participants provided blood samples from 1982 to 1984 (mean age 57 yr). Using stored samples, we measured free IGF-I in 376 men and total IGF-I and IGF binding protein-3 in 460 men. Starting in 2001, we administered telephone-based tests of general cognition [the Telephone Interview of Cognitive Status (TICS)], verbal memory, and category fluency. We estimated multivariable-adjusted mean differences in cognitive performance across levels of free IGF-I and IGF-I to IGF binding protein-3 molar ratio. Main Outcome Measures: Global score (averaging performance across all individual cognitive tests), the TICS, and a verbal memory score were measured. Results: Each sd increment in free IGF-I was associated with a multivariable-adjusted increase of 0.08 U (P = 0.02) on the global score. This mean difference was equivalent to that observed between men 2 yr apart in age: i.e. each sd increase in free IGF-I appeared cognitively equivalent to staying 2 yr younger. No significant mean differences in TICS scores were observed across free IGF-I levels. For verbal memory, each sd increment in free IGF-I was associated with an adjusted mean difference of 0.08 U (P = 0.03). Results appeared consistent for the molar ratio but were not statistically significant. Conclusion: Higher midlife free IGF-I may be associated with better late-life cognition.