Under these conditions, an inadequate trophic support to brain may occur due to lower insulin/IGF-1 levels and/or damaged IR/IGF-1R-mediated signaling, affecting gene transcription and culminating in neurodegeneration/death, cognitive dysfunction, and, ultimately, in long-term complications (in case of diabetes) and/or in AD (and other dementia) [46]. Here, IGF1 is linked to Alzheimer disease.