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Impaired cerebral autoregulation in primary biliary cirrhosis: implications for the pathogenesis of cognitive decline

Lookup NU author(s): Dr Kieren Hollingsworth, Professor David Jones, Professor Roy Taylor, Dr James FrithORCiD, Professor Andrew BlamireORCiD, Emerita Professor Julia Newton


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Background Cognitive impairment is recognised in the early stages of primary biliary cirrhosis (PBC). Aims To determine the mechanisms that underlie the cognitive dysfunction that can occur in early-stage PBC, with a particular focus on the role of autonomic dysfunction and altered cerebral autoregulation. Patients Early-stage PBC patients, and age- and sex-matched controls. Interventions and main outcome measures Brain magnetic resonance imaging to determine the relationship between structural brain abnormalities (T-2) and cerebral vasculature responsiveness assessed using the Valsalva manoeuvre. Dynamic assessment of cerebral vascular flow using transcranial Doppler was also performed in PBC subjects to derive the pulsatility index (a marker of cerebral resistance) and the autoregulatory slope index [ASI; ratio between the cerebral blood flow velocity and blood pressure (BP)]. Results Cerebral resistance was increased (P=0.04), and cerebral autoregulation in response to the Valsalva was significantly impaired in the PBC group with markedly lower mean ASI values compared with the controls (7.8 +/- 7.0 vs -8.5 +/- 8.4; P=0.002). All controls had normal cerebral autoregulation compared with only 20% of the PBC group. Indicators of sympathetic failure (BP change between Valsalva phases III-IV and low-frequency heart rate variability) correlated with increasing globus pallidus (GP) T-2 values (P < 0.05), beyond the effect of age. Conclusion This study demonstrates the presence of increased cerebral vascular resistance and abnormal cerebral autoregulation in PBC patients, and identifies a potentially important association between the degree of abnormality in structural changes in the GP. These findings suggest that organic brain injury in PBC is directly related to autonomic dysfunction.

Publication metadata

Author(s): Hollingsworth KG, Jones DEJ, Taylor R, Frith J, Blamire AM, Newton JL

Publication type: Article

Publication status: Published

Journal: Liver International

Year: 2010

Volume: 30

Issue: 6

Pages: 878-885

Print publication date: 13/05/2010

ISSN (print): 1478-3223

ISSN (electronic): 1478-3231

Publisher: Wiley-Blackwell Publishing Inc.


DOI: 10.1111/j.1478-3231.2010.02259.x


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