Blood- brain barrier permeability in cases of post-operative delirium is associated with central nervous system phosphatidylcholine imbalances

Blood-brain barrier (BBB) permeability is reportedly increased in patients exhibiting postoperative delirium. Changes in either cerebrospinal fluid (CSF) or blood metabolites have also been reported in cases of delirium. This investigation examined whether BBB permeability influences metabolite concentrations on either side of the barrier, and whether this changes in cases of delirium. This study is a nested case-control cohort (n = 54) drawn from the entire cohort of n = 315 participants. Preoperative CSF and plasma from postoperative delirium and control participants matched for age and gender underwent metabolomic profiling. Concentrations of metabolites in plasma and in CSF were obtained, and where measurable, a CSF/plasma metabolite ratio (Qmetab) was calculated. CSF/plasma albumin ratio (Qalb), a recognized indicator of BBB permeability, was also calculated. The above parameters were compared between delirium and control groups. Finally, each Qmetab was correlated against Qalb for control or delirium cases. In cases where delirium would later occur there were significant elevations in the Qmetabs of amino acids (Gln, His, Met, Phe, Tyr and Val), and one phosphatidylcholine (PC). Many other PC Qmetabs significantly correlated with Qalb and this mainly occurred in individuals subsequently experiencing delirium. In persons prone to postoperative delirium, the equilibrium of certain species of PC across the BBB correlates with BBB permeability. It is unclear whether this occurs because of changes in PC metabolism or transit, but understanding this could improve our understanding of the mechanisms underlying delirium.