Common neurodegenerative pathways in brain aging, cognitive decline, type 2 diabetes & metabolic syndrome

Aging and age-related diseases share several biological mechanisms, forming a finely controlled network where inflammation plays an encompassing key role. In the Central Nervous System (CNS), glial cells can modulate neuroinflammation by promoting neuronal homeostasis and limit neurodegeneration. However, age-related systemic inflammation (i.e. inflammaging) leads to additional deteriorations of both microglia and astrocytes causing an exacerbation response of these cells to stimuli. Type 2 diabetes (T2DM), a chronic metabolic disorder characterized by hyperglycemia, has also been associated with multiple organs loss, including the brain. Numerous studies have underlined direct correlations between diabetes, cognitive decline and dementia, however exact mechanisms related to neurodegeneration in T2DM remain to be elucidated. It widely recognized that aging is considered the most critical risk factor for Alzheimer's disease (AD), however there are increasing data highlighting that metabolic disorders are also strongly associated with an increased risk of AD and T2DM. Indeed, impaired glucose metabolism and mitochondrial activity are common grounds for cognitive dysfunction and AD. The Metabolic syndrome (MetS) in mid-life may accelerate the progression of AD pathogenesis by activating an increased productions neuroinflammatory biomarkers leading to amyloid pathology degeneration. There remains an intricate crosstalk between the aging process, T2DM, MetS, and neuroinflammation, thus resulting in neuronal loss and the development of cognitive impairment with an accelerated risk of AD. Future studies are needed to identify potential therapeutic benefits related to improving neuroinflammation on cognitive performance.