Abstract

BACKGROUND: Patients with minimal hepatic encephalopathy (MHE) show mild cognitive impairment associated with cognitive alterations and changes in connectivity. We assessed the relationship of abnormalities of resting-state functional connectivity (rs-FC) and gray matter (GM) volume with cognitive alterations and biochemical parameters associated to MHE. We also evaluated the relationship between memory in MHE and structural and functional connectivity (FC) changes in the hippocampal system. METHODS: Twenty-six cirrhotic patients without MHE (NMHE), 13 with MHE, and 24 controls were cognitive assessed with a battery of psychometric tests. Atrophy was determined using Voxel-Based Morphometry and rs-FC was assessed by ICA analysis. Receiver operating characteristic (ROC) curves was performed to assess the diagnostic utility of rs-FC and GM reduction for the discrimination of patients with and without MHE. We also assessed the relationship between alterations in memory and the structural integrity and FC of the hippocampal system. RESULTS: MHE patients showed significant decrease of GM volume and lesser degree of rs-FC in different networks related to attention and executive functions as compared to controls and NMHE. There is a progressive reduction in rs-FC in the default mode network with the progression of cognitive impairment. MHE patients showed GM reduction in right frontal lobe, right insula and right cerebellum compared to NMHE patients. Alterations in GM volume and rs-FC correlated with cognitive tests. MHE patients showed impairments in learning, memory, and recognition, compared to NMHE and controls. Cirrhotic patients showed reduced fimbria volume compared to controls. Larger volumes in hippocampus subfields were related to better memory performance in NMHE patients and controls. MHE patients presented lower FC between the L-presubiculum and L-precuneus than NMHE patients, and a reduced FC between L-presubiculum and subiculum seeds and bilateral precuneus, which correlated with cognitive impairment and memory performance. CONCLUSIONS: Decreased cognitive performance is associated by reduced rs-FC and GM atrophy in MHE patients. These changes could have predictive value for detecting MHE. Alterations in the FC of the hippocampal system could contribute to learning and long-term memory impairments in MHE patients. This study shows the association between alterations in learning and long-term memory and structural and FC disturbances in hippocampal structures in cirrhotic patients. Supported by Ministerio Economía, Industria y Competitividad - Instituto Salud Carlos III (FIS PI15/00035; FIS PI18/00150) to CM; Consellería Educación Generalitat Valenciana (PROMETEOII/2014/033; PROMETEU/2018/051 to VF, CM; ACIF/2018/284 to JJG), co-funded with European Regional Development Funds (ERDF).

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