Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Abstract

Cognitive frailty, defined as the coexistence of mild cognitive impairment symptoms and physical frailty phenotype in older persons, is increasingly considered the main geriatric condition predisposing to dementia. Recent studies have demonstrated that gut microbiota may be involved in frailty physiopathology by promoting chronic inflammation and anabolic resistance. The contribution of gut microbiota to the development of cognitive impairment and dementia is less defined, even though the concept of “gut–brain axis” has been well demonstrated for other neuropsychiatric disorders. The aim of this systematic review was to summarize the current state-of-the-art literature on the gut microbiota alterations associated with cognitive frailty, mild cognitive impairment and dementia and elucidate the effects of pre- or probiotic administration on cognitive symptom modulation in animal models of aging and human beings. We identified 47 papers with original data (31 from animal studies and 16 from human studies) suitable for inclusion according to our aims. We concluded that several observational and intervention studies performed in animal models of dementia (mainly Alzheimer’s disease) support the concept of a gut–brain regulation of cognitive symptoms. Modulation of vagal activity and bacterial synthesis of substances active on host neural metabolism, inflammation and amyloid deposition are the main mechanisms involved in this physiopathologic link. Conversely, there is a substantial lack of human data, both from observational and intervention studies, preventing to formulate any clinical recommendation on this topic. Gut microbiota modulation of cognitive function represents, however, a promising area of research for identifying novel preventive and treatment strategies against dementia.

Crosstalk Between the Gut Microbiome and Bioactive Lipids: Therapeutic Targets in Cognitive Frailty

“…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). This composite phenotype is associated with an increased risk of adverse health outcomes such as falls, disability, hospitalization, institutionalization, and mortality (2,3). Older adults with cognitive frailty also have a higher risk of dementia, limitations in the activities of daily life, and lower quality of life (3).…”

“…This composite phenotype is associated with an increased risk of adverse health outcomes such as falls, disability, hospitalization, institutionalization, and mortality (2,3). Older adults with cognitive frailty also have a higher risk of dementia, limitations in the activities of daily life, and lower quality of life (3).…”

“…From a pathophysiological point of view, multiple factors are involved in the onset of cognitive frailty, including lowgrade chronic inflammation, hormonal dysregulation (i.e., hypogonadism and hypovitaminosis D), malnutrition (e.g., low diet quantity/quality), and anorexia of aging (3,4). Pathological changes in the vascular, neuro-musculoskeletal, and metabolic systems also increase the risk of cognitive frailty, cardiovascular disease, cardiac dysfunction, depression, sarcopenia, insulin resistance, and dyslipidemia (3,4). These biophysiological factors and disorders are associated with the onset of cognitive frailty but also with the imbalance of the gut microbiome, the microorganism complex that inhabits the gastrointestinal tract (8,9).…”

“…In the last decade, extensive research has focused on determining the role of the gut microbiome in host health (10). Many studies associate gut dysbiosis-the loss of microbe species richness and increased interindividual variability (9)-with the onset of several pathological diseases involving not only the gastroenteric system but also distant organs (3,(11)(12)(13). Changes in gut microbiota composition are associated with aging (14), with indices of age-related inflammation (14,15), and with a higher risk of inflammatory bowel disease and irritable bowel syndrome (16).…”

“…Changes in gut microbiota composition are associated with aging (14), with indices of age-related inflammation (14,15), and with a higher risk of inflammatory bowel disease and irritable bowel syndrome (16). In addition, other extra-gastrointestinal diseases such as atherosclerosis, metabolic syndrome, hypertension, type 2 diabetes, and neuromusculoskeletal diseases (i.e., cachexia and frailty) are also associated with gut dysbiosis (3,11,(17)(18)(19)(20)(21). Imbalance of the gut microbiome is also associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease (22)(23)(24)(25) and multiple sclerosis (26,27) (Figure 1).…”