ABSTRACT
UNLABELLED: 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.
Subject(s)
Cognition Disorders/etiology , Liver Cirrhosis, Biliary/physiopathology , Liver Cirrhosis, Biliary/psychology , Aged , Autonomic Nervous System Diseases/etiology , Autonomic Nervous System Diseases/physiopathology , Baroreflex , Brain/pathology , Cognition , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Cohort Studies , Female , Heart Rate , Humans , Liver Cirrhosis, Biliary/complications , Liver Cirrhosis, Biliary/diagnosis , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Prevalence , Sickness Impact Profile , Time FactorsABSTRACT
BACKGROUND AND AIMS: Autonomic dysfunction has previously been described in primary biliary cirrhosis patients. In nonhepatic diseases, fatigue is associated with autonomic dysfunction and impaired baroreflex sensitivity. Here, we investigate the prevalence of autonomic dysfunction using highly sensitive detection modalities and its relationship with fatigue in both noncirrhotic and cirrhotic primary biliary cirrhosis patients. METHODS: Autonomic reflex tests were performed, using continuous blood pressure and electrocardiograph measurement in 47 primary biliary cirrhosis patients and age and sex-matched controls. Fatigue was measured using the primary biliary cirrhosis-40. RESULTS: In all, 100% of precirrhotic and 81% of cirrhotic primary biliary cirrhosis patients exhibited autonomic dysfunction. Valsalva ratio and 30 : 15 ratio (measures of parasympathetic autonomic dysfunction) were significantly lower in primary biliary cirrhosis patients than in controls (valsalva ratio: 1.42 vs. 1.57; P=0.01, 30 : 15: 1.1 vs. 1.2; P=0.01). Blood pressure drop on standing (sympathetic autonomic dysfunction) was greater in the primary biliary cirrhosis group (31+/-22 vs. 23+/-15 mmHg; P=0.03). Valsalva phase IV size was similar between primary biliary cirrhosis patients and controls, however, time to phase IV was significantly longer (P=0.01), suggesting adrenergic failure. Increasing fatigue was associated with impaired baroreflex sensitivity and an earlier, bigger phase IV (sympathetic overactivity). No significant differences were seen, between cirrhotic and noncirrhotic patients. CONCLUSION: The prevalence of autonomic dysfunction in primary biliary cirrhosis patients is significantly higher than has previously been thought to be the case. Indeed, when sensitive detection modalities are used, it is found to be almost universal at all stages of the disease process. Fatigue in primary biliary cirrhosis is associated with abnormalities of autonomic function.
Subject(s)
Autonomic Nervous System Diseases/etiology , Fatigue/etiology , Liver Cirrhosis, Biliary/complications , Aged , Autonomic Nervous System Diseases/diagnosis , Baroreflex , Case-Control Studies , Fatigue/physiopathology , Female , Humans , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Liver Cirrhosis, Biliary/physiopathology , Middle Aged , Severity of Illness IndexABSTRACT
A retrospective study was conducted to investigate whether the use of low-contrast stimuli in addition to the standard high-contrast stimuli would increase the sensitivity of the pattern-reversal P100 when testing for multiple sclerosis (MS) and optic neuritis (ON). We found that there was a statistically significant increase in the number of abnormal results when using 25' checks, but not for 50' checks. Examination of patient records showed that VEP abnormalities to low-contrast stimuli only was not prognostic for subsequent development of multiple sclerosis.
