Neutrophil-Mediated Progression of Mild Cognitive Impairment to Dementia

Cognitive impairment is a serious condition that begins with amnesia and progresses to cognitive decline, behavioral dysfunction, and neuropsychiatric impairment. In the final stage, dysphagia and incontinence occur. There are numerous studies and developed drugs for cognitive dysfunction in neurodegenerative diseases, such as Alzheimer’s disease (AD); however, their clinical effectiveness remains equivocal. To date, attempts have been made to overcome cognitive dysfunction and understand and delay the aging processes that lead to degenerative and chronic diseases. Cognitive dysfunction is involved in aging and the disruption of inflammation and innate immunity. Recent reports have indicated that the innate immune system is prevalent in patients with AD, and that peripheral neutrophil markers can predict a decline in executive function in patients with mild cognitive impairment (MCI). Furthermore, altered levels of pro-inflammatory interleukins have been reported in MCI, which have been suggested to play a role in the peripheral immune system during the process from early MCI to dementia. Neutrophils are the first responders of the innate immune system. Neutrophils eliminate harmful cellular debris via phagocytosis, secrete inflammatory factors to activate host defense systems, stimulate cytokine production, kill pathogens, and regulate extracellular proteases and inhibitors. This review investigated and summarized the regulation of neutrophil function during cognitive impairment caused by various degenerative diseases. In addition, this work elucidates the cellular mechanism of neutrophils in cognitive impairment and what is currently known about the effects of activated neutrophils on cognitive decline.