Cognitive impairment in primary biliary cirrhosis: symptom impact and potential etiology.
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).


CONCLUSIONS
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.
Liver Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
Julia L
JL
Newton
Kieren G
KG
Hollingsworth
Roy
R
Taylor
Ahmed M
AM
El-Sharkawy
Zia Uda
ZU
Khan
Ruth
R
Pearce
Kathryn
K
Sutcliffe
Oke
O
Okonkwo
Adrian
A
Davidson
Jennifer
J
Burt
Andrew M
AM
Blamire
David
D
Jones
D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D017704:Baroreflex; D001921:Brain / Q000473:pathology; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D006339:Heart Rate; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D015995:Prevalence; D018434:Sickness Impact Profile; D013997:Time Factors