Increased neuronal activation and cognitive performance by detemir as compared to human insulin upon a working memory task – an fMRI study

Growing evidence suggests that insulin improves neurocognitive functioning in patients with Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Recent studies indicate differential neuronal activation upon insulin application. Particularly the insulin analogue detemir exert some beneficial effects on neuronal activation and cognitive performance. In a randomized cross-over, single-blind, fMRI trial we investigate neuronal activation in 16 T2DM patients and 17 healthy controls (HC) during an n-back task for working memory, under conditions of actrapid, detemir, or placebo application by euglycemic glucose clamping. We demonstrate increased activation in working memory-related brain regions in T2DM patients as compared to HC under all conditions (p < 0.001). Actrapid, and more intense detemir, led to increased activation in these regions as compared with placebo (p < 0.001). We found a lower error rate during detemir condition in HC as compared to T2DM (p = 0.007). In HC, detemir also lowered error rates as compared to placebo (p = 0.017) and actrapid (p = 0.049). Actrapid, and more intense detemir, enhanced the BOLD response in T2DM as compared to HC. Detemir improved cognitive performance in HC. These data demonstrate superior beneficial effects of detemir over actrapid in terms of neuronal activation and working memory performance in T2DM and HC. So insulin application, particularly detemir, is a promising option to combat neurocognitive dysfunction in AD and T2DM.