Abstract

Cognitive frailty is a geriatric condition defined by the coexistence of cognitive impairment and physical frailty. This “composite” aging phenotype is associated with a higher risk of several adverse health-related outcomes, including dementia. In the last decade, cognitive frailty has gained increased attention from the scientific community that has focused on understanding the clinical impact and the physiological and pathological mechanisms of development and on identifying preventive and/or rehabilitative therapeutic interventions. The emergence of gut microbiome in neural signaling increased the interest in targeting the gut–brain axis as a modulation strategy. Multiple studies on gastroenteric, metabolic, and neurodegenerative diseases support the existence of a wide bidirectional communication network of signaling mediators, e.g., bioactive lipids, that can modulate inflammation, gut permeability, microbiota composition, and the gut–brain axis. This crosstalk between the gut–brain axis, microbiome, and bioactive lipids may emerge as the basis of a promising therapeutic strategy to counteract cognitive frailty. In this review, we summarize the evidence in the literature regarding the link between the gut microbiome, brain, and several families of bioactive lipids. In addition, we also explore the applicability of several bioactive lipid members as a potential routes for therapeutic interventions to combat cognitive frailty.

Highlights

  • Cognitive frailty is an intermediate neuro-degenerative state defined by the coexistence of physical frailty syndrome and cognitive impairment in the absence of a clinical diagnosis of Alzheimer’s disease or other types of dementia [1]

  • We only focused on four bioactive lipid families due to their roles in immunity and inflammation and their associations with several chronic diseases that are involved in the onset of cognitive frailty [3, 4]

  • Despite the number of interesting reviews [3, 16, 60, 64, 88, 92, 93, 98], to date, there have been no studies focusing on the interaction between these three components: gut microbiota, bioactive lipids, and cognitive frailty

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Summary

Frontiers in Nutrition

Cognitive frailty is a geriatric condition defined by the coexistence of cognitive impairment and physical frailty This “composite” aging phenotype is associated with a higher risk of several adverse health-related outcomes, including dementia. The emergence of gut microbiome in neural signaling increased the interest in targeting the gut–brain axis as a modulation strategy. Metabolic, and neurodegenerative diseases support the existence of a wide bidirectional communication network of signaling mediators, e.g., bioactive lipids, that can modulate inflammation, gut permeability, microbiota composition, and the gut–brain axis. This crosstalk between the gut–brain axis, microbiome, and bioactive lipids may emerge as the basis of a promising therapeutic strategy to counteract cognitive frailty.

INTRODUCTION
PHOSPHOLIPIDS AND SPHINGOLIPIDS
TARGETING BIOACTIVE LIPIDS AS A THERAPEUTIC STRATEGY FOR COGNITIVE FRAILTY
ENDOCANNABINOIDS AS THERAPEUTIC TARGETS
CONCLUSION AND FUTURE DIRECTIONS
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