Fasting Insulin Levels and Cognitive Decline in Older Women without Diabetes

<i>Background:</i> Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women. <i>Methods:</i> Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses’ Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70–75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline. <i>Results:</i> Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, –0.06 (–0.16, 0.03), –0.14 (–0.24, –0.04), and –0.09 (–0.19, 0.01) points (p trend = 0.04); verbal memory, –0.01 (–0.04, 0.02), –0.05 (–0.08, –0.02), and –0.02 (–0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment. <i>Conclusions:</i> Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes.