Cognitive impairment in primary biliary cirrhosis: Symptom impact and potential etiology

Abstract

Qualitative studies suggest that patients with primary biliary cirrhosis (PBC) experience significant problems with memory and concentration. Studies of nonhepatic disease have linked hypotension and cognitive impairment. In this study, we determined the prevalence of cognitive symptoms in PBC, examined the relationship between symptoms and overt cognitive impairment and structural brain lesions, and explored the role of autonomic dysfunction. The prevalence of cognitive symptoms was determined in 198 patients with PBC. Twenty-eight representative early-stage female patients with PBC and 11 matched controls underwent formal cognitive testing at baseline and after 2 years of follow-up. Autonomic nervous system function was assessed according to heart rate variability and baroreflex sensitivity. Eleven subjects with PBC had structural brain lesions quantified via magnetic resonance imaging. Cognitive symptoms were frequent in our PBC population, with 53% of patients experiencing moderate or severe problems with concentration and/or memory, which were unrelated in their severity to biochemical and histological makers of liver disease severity, suggesting that this symptom burden is largely or entirely unrelated to hepatic encephalopathy. Perceived cognitive symptoms correlated with objectively assessed cognitive impairment (r 2 ‫؍‬ 0.2, P < 0.05). Cognitive deficits were seen in the PBC cohort compared with controls, with significant decline detected over 2 years of follow-up. Correlations were seen between cognitive performance (full-scale intelligence quotient) and systolic blood pressure (P ‫؍‬ 0.01, r 2 ‫؍‬ 0.2) with decline in cognitive function associated with autonomic abnormalities. Structural brain lesions were found in PBC, the density of which correlated with degree of cognitive impairment (P ‫؍‬ 0.01, r 2 ‫؍‬ 0.5) and autonomic function (P ‫؍‬ 0.03, r 2 ‫؍‬ 0.2). Conclusion: Cognitive symptoms are prevalent in PBC independent of liver disease severity and are associated with poorer performance on objective cognitive testing. Cognitive impairment is, in turn, associated with structural brain lesions and autonomic dysfunction, which may predict risk of cognitive decline. (HEPATOLOGY 2008;48:541-549.) P rimary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with an autoimmune etiology. 1 In addition to the risk of progressive liver disease, culminating in biliary cirrhosis with its associated complications, patients frequently experience non-stage-associated symptoms that can often lead to significant impairment of their quality of life. [2][3][4][5][6] Research into the non-end-stage disease-associated factors that lead to impairment of quality of life in PBC has, to date, largely focused on fatigue; a symptom which affects a significant proportion of patients and which is associated with impairment in normal physical functioning. 7-10 However, patient reports, and qualitative studies performed in the derivation of a PBC-specific quality of life measure, the PBC-40, suggest the existence of...

Impact of primary biliary cirrhosis on perceived quality of life: The UK-PBC national study

“…Evidence in favor of an organic CNS process in PBC comes from brain imaging data and neurophysiology studies which suggest the presence of organic brain change. 24,28 In the current study autonomic symptoms associated strongly with cognitive symptoms, fatigue, and with sleep disturbance. The strong associations between autonomic dysfunction, fatigue, problems with cognition, and problems with sleep regulation all provide further support for at least some organic CNS element underpinning the symptom complex in PBC.…”

“…There are independent strands of evidence from imaging and neurophysiological studies to implicate organic CNS disturbance in the disease expression. 23,24 Given the observations that regardless of cause, fatigue is the symptom with the greatest impact in PBC ( Fig. 2A), yet social symptoms are those linked most closely to perceived QOL (Table 2), we explored the interrelationship between these symptoms in the expression of life-quality impairment.…”

Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study

“…This finding pointed to potentially irreversible and progressive brain impairment in PBC patients, and it was supported with the results of the other studies. Newton et al and Firth et al noticed that cognitive symptoms (memory and concentration) were prevalent in PBC independently of liver disease severity [27,38], similarly to findings from this recent study. On the other hand cognitive impairment indicated the role of autonomic dysfunction.…”

“…Cognitive impairment in PBC patients was previously reported by groups of Raszeja-Wyszomirska et al [26] and Newton et al [27] as the symptom independent of liver disease severity and associated with poorer performance on objective cognitive testing. Cognitive impairment was, in turn, associated with structural brain lesions and autonomic dysfunction, which might predict risk of cognitive decline in the study of Newton et al [27] Brain perfusion scintigraphy provides dynamic, functional measures of brain function based on regional cerebral blood flow and tracer accumulation in brain grey matter compared with the static, structural data provided by conventional computerized axial tomography or magnetic resonance imaging (MRI). Mental fatigue was related to brain activity during the fatiguing cognitive task and significant positive relationships were found for cerebellar, temporal, cingulate and frontal regions on MRI [28].…”

“…The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred [24,25]. Cognitive impairment in PBC patients was previously reported by groups of Raszeja-Wyszomirska et al [26] and Newton et al [27] as the symptom independent of liver disease severity and associated with poorer performance on objective cognitive testing. Cognitive impairment was, in turn, associated with structural brain lesions and autonomic dysfunction, which might predict risk of cognitive decline in the study of Newton et al [27] Brain perfusion scintigraphy provides dynamic, functional measures of brain function based on regional cerebral blood flow and tracer accumulation in brain grey matter compared with the static, structural data provided by conventional computerized axial tomography or magnetic resonance imaging (MRI).…”