title: Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy.
abstract: To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE). We analyzed the presence of mild cognitive impairment (CI) by using the PHES battery of psychometric tests and measured the levels of ammonia and of the inflammatory cytokines IL-6 and IL-18 in blood of patients with different types of liver or dermatological diseases resulting in different grades of hyperammonemia and/or inflammation. The study included patients with 1) liver cirrhosis, showing hyperammonemia and inflammation; 2) non-alcoholic fatty liver disease (NAFLD) showing inflammation but not hyperammonemia; 3) non-alcoholic steatohepatitis (NASH) showing inflammation and very mild hyperammonemia; 4) psoriasis, showing inflammation but not hyperammonemia; 5) keloids, showing both inflammation and hyperammonemia and 6) controls without inflammation or hyperammonemia. The data reported show that in patients with liver diseases, cognitive impairment may appear before progression to cirrhosis if hyperammonemia and inflammation are high enough. Five out of 11 patients with NASH, without liver cirrhosis, showed cognitive impairment associated with hyperammonemia and inflammation. Patients with keloids showed cognitive impairment associated with hyperammonemia and inflammation, in the absence of liver disease. Hyperammonemia or inflammation alone did not induce CI but the combination of certain levels of hyperammonemia and inflammation is enough to induce CI, even without liver disease.
authors.affiliation: Laboratory of Neurobiology. Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
authors.forename: Amparo
authors.initials: A
authors.lastname: Urios
authors.forename: Encarna
authors.initials: E
authors.lastname: Montesinos
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Molina
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia-Torres
authors.forename: Miguel
authors.initials: M
authors.lastname: Civera
authors.forename: Juan A Del
authors.initials: JA
authors.lastname: Olmo
authors.forename: Joaquin
authors.initials: J
authors.lastname: Ortega
authors.forename: Jose
authors.initials: J
authors.lastname: Martinez-Valls
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Serra
authors.forename: Norberto
authors.initials: N
authors.lastname: Cassinello
authors.forename: Abdallah
authors.initials: A
authors.lastname: Wassel
authors.forename: Esperanza
authors.initials: E
authors.lastname: Jordá
authors.forename: Carmina
authors.initials: C
authors.lastname: Montoliu
mesh_terms: D000328:Adult; D000368:Aged; D000641:Ammonia / Q000097:blood*; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood / Q000150:complications* / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000150:complications* / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007627:Keloid / Q000097:blood / Q000150:complications / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D065626:Non-alcoholic Fatty Liver Disease; D011565:Psoriasis / Q000097:blood / Q000150:complications / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D020382:Interleukin-18; D015850:Interleukin-6; D000641:Ammonia
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