Abstract
BACKGROUND: Both type 2 diabetes and hyperinsulinemia have been related to diminished cognition. To address independent effects of increasing mid-life insulin secretion on late-life cognition, we prospectively examined the relation of plasma C-peptide levels to cognitive decline in a large sample of older women without diabetes or stroke. METHODS: Plasma C-peptide levels were measured in 1187 "young-old" women (mean age=64 years) without diabetes in the Nurses' Health Study. Cognitive decline was assessed approximately 10 years later. Three repeated cognitive batteries were administered over an average of 4.4 years using telephone-based tests of general cognition, verbal memory, category fluency, and attention. Primary outcomes were general cognition (measured by the Telephone interview for Cognitive Status [TICS], as well as a global score averaging all tests) and a verbal memory score averaging four tests of word-list and paragraph recall. Linear mixed effects models were used to compute associations between C-peptide levels and rates of cognitive decline. RESULTS: Higher C-peptide levels were associated with faster decline in global cognition and verbal memory. Compared to those in the lowest C-peptide quartile, multivariable-adjusted mean differences (95% CI) in rates of decline for women in the highest quartile were -0.03 (-0.06,-0.00) units/year for the global score, and -0.05 (-0.09,-0.02) units/year for verbal memory. Each one standard-deviation increase in C-peptide was associated with significantly faster decline on the TICS (p-trend=0.05), global score (p-trend=0.04) and verbal memory (p-trend=0.006). CONCLUSIONS: Higher levels of insulin secretion in those without diabetes may be related to decline in general cognition and verbal memory.