BACKGROUND: Glucose poses the predominant energy source of the brain and its continuous uptake is vital for optimal brain function. Neurons metabolize glucose to generate adenosine triphosphate via glycolysis and the tricarboxylic acid cycle, whereas astrocytes utilize glucose both as an energy source and to generate glutamine - a neurotransmitter precursor- for neurons [Brekke et al., 2015]. Here, we prospectively examine the relationship between chronic hypoglycemia and the associated links between neurodegeneration and dementia. It is proposed that severe episodes or chronic hypoglycemia will induce an increased risk of dementia. METHODS: A complex and specific literature search was conducted across various scientific, international databases for English, peer-reviewed articles and reviews published in the last two decades using the following terms: diabetes, insulin, glucose metabolism, hypoglycemia, and Alzheimer's disease (AD). Case reports were excluded. The main objectives were predominantly focused on animal- or human-based studies. RESULTS: When blood glucose levels are