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Impaired cerebral autoregulation in primary biliary cirrhosis: implications for the pathogenesis of cognitive decline
Author(s) -
Hollingsworth Kieren G.,
Jones David E. J.,
Taylor Roy,
Frith James,
Blamire Andrew M.,
Newton Julia L.
Publication year - 2010
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2010.02259.x
Subject(s) - cerebral autoregulation , cerebral blood flow , medicine , valsalva maneuver , cardiology , autoregulation , transcranial doppler , primary biliary cirrhosis , cerebral circulation , blood pressure
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.