Current Understanding of Long-Term Cognitive Impairment After Sepsis

Abstract

Sepsis is recognized as a life-threatening multi-organ dysfunction resulting from a dysregulated host response to infection. Although the incidence and mortality of sepsis decrease significantly due to timely implementation of anti-infective and support therapies, accumulating evidence suggests that a great proportion of survivors suffer from long-term cognitive impairment after hospital discharge, leading to decreased life quality and substantial caregiving burdens for family members. Several mechanisms have been proposed for long-term cognitive impairment after sepsis, which are not mutually exclusive, including blood-brain barrier disruption, neuroinflammation, neurotransmitter dysfunction, and neuronal loss. Targeting these critical processes might be effective in preventing and treating long-term cognitive impairment. However, future in-depth studies are required to facilitate preventive and/or treatment strategies for long-term cognitive impairment after sepsis.

Cognitive impairment is a risk factor for long-term outcomes in septic patients: A retrospective observational study

“…A recent systematic review found that cognitive impairment of sepsis survivors ranged from 12.5 to 21% [11]. Pathophysiological changes, such as blood-brain barrier dysregulation, neuroinflammation, neurotransmitter dysfunction, and neuronal loss are thought to be responsible for long-term cognitive impairments [21]. More recently, chronic conditions of sepsis-associated encephalopathy have been recognized, including memory impairment, attention deficit, language impairment, and executive dysfunction, which are present in more than half of sepsis survivors at the time of hospital discharge [22].…”

“…A recent systematic review found that cognitive impairment of sepsis survivors ranged from 12.5 to 21% [11]. Pathophysiological changes, such as blood-brain barrier dysregulation, neuroinflammation, neurotransmitter dysfunction, and neuronal loss are thought to be responsible for long-term cognitive impairments [21].…”

The Impact of COVID-19 Lockdown Measures and COVID-19 Infection on Cognitive Functions: A Review in Healthy and Neurological Populations

“…Indeed, the vast majority of research has intentionally excluded individuals with previous neurological and psychiatric disorders, who would have confounded the interpretation of the results [ 93 ]. Almost all studies reported the presence of a general cognitive decline [ 60 , 61 , 62 , 63 , 64 , 68 , 69 , 70 , 73 , 77 , 78 , 82 , 83 , 84 , 85 ] (see Table 2 ), which is a common sequela of other viral diseases, such as AIDS [ 112 , 113 ] and sepsis ([ 114 , 115 ]. In the literature, this status is often referred to as ‘Long COVID’ [ 116 , 117 ], or ‘brain fog’ with accompanied clinical symptoms, such as low energy, insomnia, problems in concentration and spatial orientation and difficulty in finding the right words [ 118 ].…”

Dexpramipexole ameliorates cognitive deficits in sepsis-associated encephalopathy through suppressing mitochondria-mediated pyroptosis and apoptosis

“…The peripheral LPS-injection animal model has been shown to induce neuroinflammation and long-term cognitive deficits and has been widely used to investigate the pathogenesis of SAE and to test potential therapeutics [7,28,29]. To investigate the effects of LPS injection on survival rate, the mice were monitored for 7 days.…”

“…SAE is associated with elevated mortality and morbidity and can cause long-term cognitive impairment in sepsis survivors, manifested mainly in declarative memory, working memory, processing speed and executive function [1][2][3]. To date, several animal models, including those based on lipopolysaccharide (LPS) injection and cecal ligation puncture, have been widely used to mimic clinical human sepsis in preclinical studies [4][5][6][7]. However, the precise pathological mechanisms underlying long-term cognitive impairment after sepsis remain largely unknown, and effective treatments are lacking [8].…”