Anesthetic Drugs as a Pharmacologic Stress Test for the Aging Brain: Towards a Real Time EEG Read‐Out

Abstract

AbstractBackgroundRoughly 65 million older adults (ie age >65 years) undergo anesthesia/surgery each year and are at risk for postoperative delirium. Further, postoperative delirium is itself associated with increased long term risk for Alzheimer’s Disease and Related Dementias (ADRD). Recent work has also shown that some patients have deeply suppressed neurophysiologic (ie EEG) patterns in response to relatively low anesthetic drug doses, and that these patients are more likely to have preoperative cognitive impairment and to develop postoperative delirium. However, to date few if any studies have examined the role of specific ADRD pathologic processes and neuroimaging abnormalities in these altered anesthetic dose‐dependent EEG response patterns in older adults.MethodWe examined relationships between intraoperative 32 channel EEG data (in cognitively normal older non‐cardiac surgery patients who received inhaled anesthetics such as isoflurane) and both 1) preoperative CSF ADRD biomarker levels and 2) preoperative structural and functional MRI imaging characteristics. CSF abeta, tau and p‐tau‐181p were measured using the Roche elecsys platform. Frontal‐parietal alpha band phase lag index and alpha power were calculated from frontal and parietal electrode regions of interest (ROIs), and normalized to inhaled anesthetic dosage.ResultLower anesthetic dose‐adjusted frontal‐parietal alpha band phase lag index values were associated with higher preoperative CSF p‐tau/Ab ratios (p = 0.013, N = 9‐18 per group, Fig 1A), lower cortical thickness in the left and right parahippocampal regions (Fig 1B, N = 16, p<0.001), and altered resting state fMRI connectivity between the left anterior entorhinal cortex and both the left medial prefrontal cortex and the left angular gyrus (two key default mode network regions; Fig 1C, N = 16, peak voxel p<0.01).ConclusionThese data suggest that both molecular markers and neuroimaging features of preclinical AD neuropathology in cognitively normal older adults are associated with altered anesthetic dose‐dependent changes in neurophysiologic/EEG functional connectivity. More generally, these data demonstrate the need for additional studies to understand the extent to which intraoperative EEG data can be used to make inferences about ADRD‐related neuropathologic processes in older adults, which could provide a real‐time EEG “readout” for the stress test of anesthesia and surgery on the aging brain