Discussion
hypoxic-ischemic brain injury, cognitive decline, cardiac arrest
BLOOD, HYPOXIC-ISCHEMIC BRAIN INJURY, CARDIAC ARREST
In this case-control study, we examined the central AD blood biomarkers, p-tau and Aβ, in patients with severe hypoxic-ischemic brain injury due to cardiac arrest. The key results demonstrate a rapid increase of p-tau into the bloodstream within 24 hours following cardiac arrest. However, this increase was highly specific to individuals exhibiting a poor neurologic outcome; individuals with a good neurological outcome exhibited minimal change. Results in the larger validation cohort showed a prognostic value similar to NfL and higher than t-tau at 24 hours; however, the direct magnitude changes of t-tau and NfL were shown to be far larger than p-tau. At 48-72 hours after cardiac arrest, p-tau levels in patients with poor neurological outcome largely decreased and approached the concentrations of patients with good neurological outcome, which remained at a normal level during this acute period.Blood p-tau is a meaningful and highly specific measure of underlying AD neuropathologyWe also found increasing blood levels of both Aβ40 and Aβ42, which were significantly different in the poor neurologic outcome group at 48 hours (Aβ42) and 72 hours (Aβ40 and Aβ42) but not at 24 hours. Visually, the temporal trajectories of Aβ42 followed a similar pattern to NfL and t-tau, albeit on a substantially lower magnitude. The Aβ42/Aβ40 ratio did not change significantly. These results support our previous pilot study showing a more than 3-fold increase in serum Aβ42 acutely after cardiac arrest and correlating with clinical outcome.It is unclear if increased concentrations of serum p-tau in cardiac arrest patients might signify a higher long-term risk of AD. Data from cognitively healthy older adults do demonstrate an increased risk of cognitive decline in individuals with higher levels of blood p-tau.