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

Division of Aging (O.I.O., J.M.G., F.G.) and Channing Laboratory (O.I.O., J.H.K., J.M., F.G.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, and the Department of Epidemiology (F.G.), Harvard School of Public Health, Boston, Massachusetts 02115; and the Veterans Affairs Boston Healthcare System (J.M.G.), Jamaica Plain, Massachusetts 02130

Address all correspondence and requests for reprints to: Dr. Olivia Okereke, Channing Laboratory, 3rd Floor, 181 Longwood Avenue, Boston, Massachusetts 02115. E-mail: ookereke{at}partners.org.

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.