Background: Worldwide, at least 2.8 million people die each year as a result of being overweight
or obese. Obesity leads to metabolic syndrome, a pathological condition characterized by
adverse metabolic effects on blood pressure, cholesterol, triglycerides and insulin resistance. Population-
based investigations have suggested that obesity and metabolic syndrome may be associated with
poorer cognitive performance.
Method: A structured search of bibliographic source (PubMed) was undertaken. The following terms
“inflammation and obesity and brain”, “cholinergic system and obesity”, “cholinergic system and
metabolic syndrome”, “Cognitive impairment and obesity” and “metabolic syndrome and brain” were
used as search strings.
Results: Over 200 papers, mainly published in the past 10 years were analysed. The major results regarded
keyword “metabolic syndrome and brain” followed by, “Cognitive impairment and obesity”,
“inflammation and obesity and brain”, “cholinergic system and obesity” and “cholinergic system and
metabolic syndrome”. Most papers were pre-clinical but, in general, they were inhomogeneous.
Therefore, the results were cited according their contribution to clarify the molecular involvement of
obesity and/or metabolic syndrome in cholinergic impairment.
Conclusion: This review focuses on the correlation between brain cholinergic system alterations and
high-fat diet, describing the involvement of cholinergic system in inflammatory processes related to
metabolic syndrome and obesity, which may lead to cognitive decline. Metabolic syndrome has been
suggested as a risk factor for cerebrovascular diseases and has been associated with cognitive impairment
in different functional brain domains. Preclinical and clinical studies have identified the cholinergic
system as a specific target of metabolic syndrome and obesity. The modifications of cholinergic
neurotransmission and its involvement in neuro-inflammation may be related to cognitive impairment
that affects obese patients.