Impaired cognition predicts the risk of hospitalization and death in cirrhosis

Abstract

Objective: Cognitive impairment, detected in up to 80% of patients with liver cirrhosis, is associated with negative health outcomes but is underdiagnosed in the clinical setting due to the lack of practical testing method. This single-center prospective observational study aimed to test the feasibility and prognostic utility of in-clinic cognitive assessment of patients with liver cirrhosis using the NIH Toolbox cognition battery (NIHTB).

Methods: Patients recruited from a hepatology/transplant clinic underwent cognitive assessments using West-Haven Grade (WHG) and NIHTB between November 2016 and August 2018 and were prospectively followed until December 2018. The primary outcome was a composite end point of hospitalization related to overt hepatic encephalopathy (OHE) and all-cause mortality during follow-up, evaluated by a Cox proportional hazards regression model that adjusted for a priori covariates (age and MELD-Na).

Results: Among 127 patients (median age 60 years, 48 [38%] women) assessed, cognitive performance was significantly impaired in 82 [78%] patients with WHG 0 and 22 [100%] patients with WHG 1 and 2. Over a median of 347 days follow-up, 18 OHE and 8 deaths were observed. Lower cognitive performance was associated with an increased risk of OHE/death adjusting for age and MELD-Na. Subclinical cognitive impairment detected by NIH Toolbox in WHG 0 patients was significantly associated with greater mortality. Median time to complete the two prognostically informative NIH Toolbox tests was 9.4 min.

Interpretation: NIH Toolbox may enable a rapid cognitive screening in the outpatient setting and identify patients at high risk for death and hospitalization for severe encephalopathy.

Figure 1

NIH Toolbox Cognition Test Results by West Haven Grade. Boxplots of T‐scores are shown for each test within the NIH Toolbox Cognitive Battery along with the mean overall score, divided by patients’ West Haven Grade. Dashed line represents demographic‐matched population norm. DCCS‐Dimensional Change Card Sort, FICA‐Flanker Inhibitory Control and Attention, LSWM‐List Sorting Working Memory, and PCPS‐Pattern Comparison Processing Speed.

Figure 2

Time from cognitive assessment to overt hepatic encephalopathy (OHE)‐related hospitalization or death. Time from cognitive screening to OHE‐related hospitalization or death showed a significant difference between patients who scored one standard deviation below the demographic‐matched norm (T‐score < 40) in the NIH Toolbox List Sort Working Memory test and those who scored equal to or greater than 40. The Kaplan–Meier curve for estimated cumulative incidence of the primary end point in the Y axis and days from initial cognitive screening in the X axis. The red lines depict patients who scored below 40 at study entry, and blue lines denote those who scored equal to or greater than 40, with each vertical line signifying censoring. Log‐rank statistics were used to compare groups. LSWM‐List Sorting Working Memory, OHE‐Overt Hepatic Encephalopathy.