Resting-State Brain Networks in Elderly Cirrhotic Patients Reveal a Distinct Brain Response to Aging

Abstract

Background: The cirrhotic population is getting older, with a significant potential overlap of covert HE with pre-dementia mild cognitive impairment (MCI). The underlying functional basis of this cognitive impairment in elderly cirrhotics is unclear and could be related to altered resting-state networks (RSNs). RSNs are anatomically separate yet functionally connected brain regions. Default mode network (DMN) resting network is affected in younger cirrhotics but RSNs is unclear in older patients is understudied. Aim: To investigate differences in resting-state functional connectivity between elderly cirrhotic patients and age-matched non-cirrhotic controls. Methods: Age-matched cirrhotics and non-cirrhotics between 65 and 85 years without current/prior OHE diagnoses/treatment, end-stage organ failures or uncontrolled neuro-psychiatric disorders were enrolled. Subjects underwent PHES, Stroop App and quality of life using sickness impact profile (SIP). All subjects then underwent resting-state fMRI. Group RSNs were created using an independent component analysis approach and group differences between these networks were tested using ‘dual-regression’. Results: 13 cirrhotic and 13 non-cirrhotics were included. The two groups did not differ significantly in age (Ctrl: 73.6 ± 5 yrs; Cirr: 70.1 ± 5 yrs, P = 0.11). Cirrhotics had worse PHES (Ctrl: −1; Cirr: −3; P = 0.05), Stroop Off + Ontime (Ctrl: 171.3 ± 32s; Cirr: 228.6 ± 69s; P = 0.01) and SIP (Ctrl: 1.4 ± 1.8; Cirr: 10.4 ± 16; P = 0.05). RSN analysis: Several group RSNs were detected but no differences on DMN were found. However, we found lower functional connectivity in elderly cirrhosis group compared to elderly controls in two important networks: (A) visual network: right lingual gyrus; P = 0.016 (important for visual processing including visual memory, word processing and selective attention), (B) dorsal/ventral attentional network: (a) left ventrolateral prefrontal cortex (left VLPFC); P = 0.004; (b) right VLPFC; P = 0.04, (c) left frontoparietal operculum (FPOC): P = 0.03 dorsal attentional network (DAN) is involved in goal-driven attention processing (top-down) whereas ventral attentional network (VAN) is involved in stimuli-driven attention processing (bottom-up). These two networks have been previously reported to be preferentially affected in amnestic mild cognitive impairment and Alzheimer's disease. Largest cluster of voxels showing group difference between cirrhotic and control group was found in the VLPFC which is part of VAN and may indicate deficits in the ability to reorient to novel or unexpected stimulus relevant information (bottom-up processing). FPOC is an area associated with verbal and spatial working memory. Conclusions: Elderly cirrhotic patients have impaired cognitive performance and quality of life compared with age-matched non-cirrhotics. This is compounded by disrupted stimulus-driven visual and attentional RSNs patterns similar to those seen in Alzheimer's-associated MCI, but not in DMN as seen in younger cirrhotics. Abnormal resting state connectivity in elderly cirrhotic patients may represent a distinct brain response to aging in the setting of cirrhosis that overlaps with MCI (Figure 1). The authors have none to declare.