Reduced resting state connectivity and gray matter volume correlate with cognitive impairment in minimal hepatic encephalopathy

PLoS One. 2017 Oct 12;12(10):e0186463. doi: 10.1371/journal.pone.0186463. eCollection 2017.

Abstract

Background and aims: Minimal hepatic encephalopathy (MHE) is associated with cognitive alterations and changes in connectivity. We assessed the relationship of the abnormalities of resting-state functional connectivity (rs-FC) and gray matter (GM) volume with different cognitive alterations and biochemical parameters associated to MHE.

Methods: Thirty-nine cirrhotic patients (26 without and 13 with MHE) and 24 controls were widely cognitive assessed with a battery of psychometric tests. Atrophy was determined using Voxel-Based Morphometry and rs-FC was assessed by independent component 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. Blood ammonia, cGMP, and levels of pro-inflammatory interleukins were measured.

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 patients without MHE. 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 the right frontal lobe, right insula and right cerebellum compared to patients without MHE. Alterations in GM volume and rs-FC correlated with the scores of different cognitive tests.

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Ammonia / blood
  • Area Under Curve
  • Case-Control Studies
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology
  • Cyclic GMP / analysis
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / physiopathology*
  • Humans
  • Interleukins / analysis
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Psychometrics
  • ROC Curve

Substances

  • Interleukins
  • Ammonia
  • Cyclic GMP

Grants and funding

Financial support was provided by Ministerio Ciencia Innovación: SAF2014-51851-R (VF) and Instituto de Salud Carlos III-FISPI15/00035 (CM), co-funded-European Regional Development Funds; Consellería Educación Generalitat Valenciana: PROMETEOII/2014/033 (VF) and ACOMP/2014/026 (CM).