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Insulin/Insulin-Like Growth Factor-1 Signaling and Cognitive Function in Humans

¹ Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
² Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.

Address correspondence to Sjoerd M. Euser, MSc, Department of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands (E-mail: s.euser{at}lumc.nl) or Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands (E-mail: s.euser{at}erasmusmc.nl)

An accumulating body of evidence suggests the involvement of an evolutionary conserved insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway in the regulation of the life and health span in nematodes, flies, rodents, and humans. We studied the association between insulin/IGF-1 signaling and cognitive function among 1015 participants, 85 years old or older, of the population-based Leiden 85-Plus Study. A composite IIS6 score, based on expected effects (increased or decreased signaling) of selected variants in the IIS pathway, was calculated to estimate IIS pathway activity. Cognitive function was assessed at baseline and annually during a 5-year follow-up, using the Mini-Mental State Examination (MMSE). In women, but not in men, lower IIS6 scores (indicating decreased signaling) were associated with a lower risk of cognitive impairment (MMSE score 18) (p trend =.010). The IIS6 score was not associated with change in cognitive function. In addition to old age survival, genetically reduced IIS seems to be beneficial for cognitive function in women.

Key Words: Insulin/IGF-1 signaling • Cognitive function • Cohort study • Human