Molecular and Biochemical Pathways Encompassing Diabetes Mellitus and Dementia

Abstract

: Diabetes mellitus is a major metabolic disorder that has now emerged as an epidemic, and it affects the brain through an array of pathways. Diabetes mellitus patients can develop pathological changes in the brain, which eventually take the shape of mild cognitive impairment progressing to Alzheimer’s Disease. A number of preclinical and clinical studies demonstrate this fact, and it comes out to be those molecular pathways such as amyloidogenesis, oxidative stress, inflammation, and impaired insulin signaling are identical in diabetes mellitus and dementia. However, the critical player involved in the vicious cycle of diabetes mellitus and dementia is insulin, whose signaling, when impaired in diabetes mellitus (both type 1 and 2), leads to a decline in cognition, although other pathways are also essential contributors. Moreover, it is not only that diabetes mellitus patients indicate cognitive decline at a later stage; many Alzheimer’s Disease patients also reflect symptoms of diabetes mellitus, thus creating a vicious cycle inculcating a web of complex molecular mechanisms and hence categorizing Alzheimer’s Disease as ‘brain diabetes’. Thus, it is practical to suggest that anti-diabetic drugs are beneficial in Alzheimer’s Disease; but only smaller trials, not the larger ones, have showcased positive outcomes mainly because of the late onset of therapy. Therefore, it is extremely important to develop more of such molecules that target insulin in dementia patients along with such methods that diagnose impaired insulin signaling and the associated cognitive decline so that early therapy may be initiated and the progression of the disease be prevented.