Relationship between CNS Tau burden and perioperative neurocognitive disorder

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Summary: Post-operative neurocognitive disorder is common after all forms of surgery in older adults. The mechanisms are multifactorial, and probably require pre-existing neuropathology, whether symptomatic or not. Preclinical and human CSF studies suggests that anesthesia and surgery elicits an increment in CNS tauopathy, which may accelerate any pre-existing neuropathology and produce a risk of delirium and the commonly reported changes in cognition. We here propose an observational clinical study at two sites to determine whether pre-operative CNS tauopathy as reflected by PET imaging predicts delirium and other cognitive and functional outcomes. This is important since these outcomes may also predict Alzheimer Disease and other dementias. Further, we will determine if anesthesia and spine surgery produces a change in brain tau burden in older adults, as compared to control, non-operative patients. We will also measure pre- and post-surgery blood biomarkers of inflammation, as well as cognitive status using detailed neuropsychological tests. The primary aims of this phased study is to first establish an integrated team, infrastructure and provide preliminary data supporting feasibility, and then to embark on a two-site observational study in approximately 30 patients and 30 controls to address the above goals.