Plasma C peptide level and cognitive function among older women without diabetes mellitus.

Background: Growing evidence suggests that type 2 diabetes mellitus and hyperinsulinemia may be related to diminished cognition. To help differentiate between the effects of diabetes and insulin, we examined the relation of insulin to cognitive function among nondiabetic participants of the Nurses' Health Study.

Methods: We measured the C peptide level, representing insulin secretion, in blood samples provided by 718 women from June 14, 1989, to October 4, 1990, when they were aged 61 to 69 years. We administered telephone interviews an average of 10 years after blood collection, testing general cognition, verbal memory, category fluency, and attention; second cognitive assessments were conducted 2 years later. The primary outcomes were global cognitive function across all tests and verbal memory. We used regression models to estimate multivariable-adjusted mean differences in cognitive function and cognitive decline, and odds of cognitive impairment, across C peptide levels.

Results: Cognitive function was worse among women in the fourth C peptide quartile compared with those in the first quartile (eg, on the global score combining all cognitive tests, the multivariable-adjusted mean difference was -1.7 standard units [95% confidence interval, -2.9 to -0.6 standard units]; P = .002); the odds of cognitive impairment (defined as the worst 10% of the distribution) were 3-fold higher among women in the fourth vs first quartile (95% confidence interval, 1.3-7.8). On verbal memory, women in the fourth quartile scored significantly worse than those in the first quartile; the odds of impairment were 2.8-fold higher (95% confidence interval, 1.1-7.0). Consistent findings were observed for cognitive decline.

Conclusion: Higher insulin secretion may be related to worse cognition, even among those without diabetes.