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Fasting Plasma Insulin, C-Peptide and Cognitive Change in Older Men without Diabetes: Results from the Physicians’ Health Study IIOkereke O.I.a, c · Kurth T.a, b, d, g, h · Pollak M.N.f · Gaziano J.M.a, b, e · Grodstein F.a, c, d
Divisions of aAging and bPreventive Medicine, and cChanning Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, and dDepartment of Epidemiology, Harvard School of Public Health, Boston, Mass., and eVA Boston Healthcare System, Jamaica Plain, Mass., USA; fDepartments of Medicine and Oncology, Lady Davis Research Institute of the Jewish General Hospital and McGill University, Montreal, Que., Canada; gINSERM U708 and hUniversité Pierre et Marie Curie, Paris, France Corresponding Author
Dr. Olivia Okereke
Channing Laboratory 3rd floor
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Background: Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline among healthy, community-dwelling older men without diabetes. Methods: Fasting plasma insulin and C-peptide (insulin secretion) levels were measured in 1,353 nondiabetic men, aged 60–92 years (mean = 71.3 years), in the Physicians’ Health Study II, who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range = 1.5–4.0 years) using telephone-based tests (general cognition, verbal memory and category fluency). Primary outcomes were the Telephone Interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging 4 verbal tests). Multivariable linear regression models were used to estimate the relations of insulin and C-peptide to cognitive decline. Results: Higher fasting insulin was associated with a greater decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency, e.g. the multivariable-adjusted mean difference (95% CI) in decline for men with the highest versus lowest insulin levels was –0.62 (–1.15, –0.09) points on the TICS (p for trend = 0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was a greater decline across all tests with increasing C-peptide, but the findings were statistically significant only for the global score (p for trend = 0.03). Conclusions: Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.
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