title: Impaired cerebral autoregulation in primary biliary cirrhosis: implications for the pathogenesis of cognitive decline.
abstract: BACKGROUND
  Cognitive impairment is recognised in the early stages of primary biliary cirrhosis (PBC).
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Early-stage PBC patients, and age- and sex-matched controls.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Kieren G
authors.initials: KG
authors.lastname: Hollingsworth
authors.forename: David E J
authors.initials: DE
authors.lastname: Jones
authors.forename: Roy
authors.initials: R
authors.lastname: Taylor
authors.forename: James
authors.initials: J
authors.lastname: Frith
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: Julia L
authors.initials: JL
authors.lastname: Newton
mesh_terms: D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001783:Blood Flow Velocity; D001794:Blood Pressure; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D004739:England; D005260:Female; D006339:Heart Rate; D006706:Homeostasis; D006801:Humans; D016014:Linear Models; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011673:Pulsatile Flow; D018570:Risk Assessment; D012307:Risk Factors; D017585:Ultrasonography, Doppler, Transcranial; D014636:Valsalva Maneuver; D014655:Vascular Resistance