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Principal Investigator: Yiying Zhang
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2024
Award: $210,348
Funding agency: National Institute on Aging
Perioperative neurocognitive disorders (PND) – including postoperative delirium, delayed neurocognitive
recovery, and postoperative neurocognitive disorders – are associated with increased morbidity and mortality,
high costs of care, and Alzheimer’s Disease and Alzheimer’s Disease Related Dementias (AD/ADRD).
Consistent with the recent findings that blood Tau-PT217 and Tau-PT181 are specific biomarkers for the early
stage of AD, our preliminary data have shown that the patients who go on to develop postoperative delirium
have more than five- and two-fold higher concentration of preoperative blood Tau-PT217 and Tau-PT181 than
the patients without postoperative delirium, respectively. In addition, blood inflammation biomarker interleukin-6
and C-reactive protein (CRP) are associated with PND. Thus, the objective of the proposed prospective cohort
study is to determine whether blood Tau-PT217 and Tau-PT181 can serve as biomarkers (primary objective) of
PND and enhancers (secondary objective) of the association between inflammation and PND. The hypothesis
is that blood inflammation biomarkers are associated with PND only in the participants with higher blood
amounts of Tau-PT217 or Tau-PT181. Because it is difficult to measure the low concentrations of pTau in
blood, we will employ a newly developed and innovative nanoneedle technology, an ultra-highly sensitive
method to detect low concentrations of molecules, to measure the Tau-PT217 and Tau-PT181 in blood. We
will establish a system for future studies by recruiting 40 participants (> 70 years old) who will have non-
cardiac surgery under general anesthesia in two Specific Aims. In Aim 1, we will establish a system to measure
Tau-PT217 and Tau-PT181 (using both nanoneedle and Simoa for comparison) and IL-6 and CRP (using both
nanoneedle and ELISA for comparison) concentrations. We will determine their relationships with the incidence
and severity of postoperative delirium on the first three days postoperatively. In Aim 2, we will use the recruited
participants in Aim 1 to investigate the associations between these blood biomarkers and delayed
neurocognitive recovery (21 days after surgery) and postoperative neurocognitive disorder (9 months after the
surgery). PNDs will be defined using 3D Confusion Assessment Method (3D-CAM) and CAM-Severity for
postoperative delirium, and neuropsychological tests for delayed neurocognitive recovery and postoperative
neurocognitive disorders. This high-impact prospective cohort study in older adults could provide vital
information for an R01 application to further establish Tau-PT217 and Tau-PT181 in blood as biomarkers and
parts of pathogenesis of PND. Such outcomes will promote the identification of patients with a higher risk of
PND, enable the determination of the effects of intervention(s) to reduce PND, and target PT217 and Tau-
PT181 in blood as the potential intervention of PND, promoting the development of strategies to prevent and
treat PND, ultimately mitigating the establishment of AD/ADRD.
Terms: <3-D><3-Dimensional><3D><AD dementia><AD related dementia><ADRD><Address><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimer's and related dementias><Alzheimer's disease and related dementia><Alzheimer's disease and related disorders><Alzheimer's disease or a related dementia><Alzheimer's disease or a related disorder><Alzheimer's disease or related dementia><Alzheimer's disease related dementia><Alzheimers Dementia><Anesthesia><Anesthesia procedures><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Biological Markers><Blood><Blood Plasma><Blood Reticuloendothelial System><Blood Sample><Blood specimen><C-reactive protein><Clinical Research><Clinical Study><Data><Detection><Development><Diagnosis><ELISA><Eligibility><Eligibility Determination><Enhancers><Enzyme-Linked Immunosorbent Assay><Future><General Anesthesia><HPGF><Hepatocyte-Stimulating Factor><Hybridoma Growth Factor><IFN-beta 2><IFNB2><IL-6><IL6 Protein><Incidence><Inflammation><Interleukin-6><Intervention><Intervention Strategies><Knowledge><L-Threonine><MGI-2><Measures><Medical Care Costs><Methods><Mission><Modeling><Morbidity><Morbidity - disease rate><Myeloid Differentiation-Inducing Protein><NIH><National Institutes of Health><Neurocognitive><Neuropsychologic Tests><Neuropsychological Tests><Operative Procedures><Operative Surgical Procedures><Outcome><Participant><Pathogenesis><Patient Recruitments><Patients><Perioperative><Plasma><Plasma Serum><Plasmacytoma Growth Factor><Post-Operative><Postoperative><Postoperative Period><Primary Senile Degenerative Dementia><Prospective, cohort study><Proteins><Proteins, specific or class, C-reactive><Protocol><Protocol Screening><Protocols documentation><Recovery><Research><Reticuloendothelial System, Serum, Plasma><Risk><Safety><Sampling><Severities><Surgical><Surgical Interventions><Surgical Procedure><System><Technology><Testing><Threonine><Time><United States National Institutes of Health><bio-markers><biologic marker><biomarker><care costs><confusion assessment method><cost><developmental><early biomarkers><early detection biomarkers><early detection markers><elderly patient><enzyme linked immunoassay><high risk><innovate><innovation><innovative><interferon beta 2><intervention effect><interventional strategy><medical costs><medical expenses><mortality><nano-needle><nanoneedle><neurocognitive disorder><novel><older adult><older adulthood><older patient><p-tau><p-τ><participant recruitment><phospho-tau><phospho-τ><phosphorylated tau><post-operative delirium><post-translational modification of tau><postoperative delirium><posttranslational modification of tau><prevent><preventing><primary degenerative dementia><primary outcome><recruit><retention rate><retention strategy><senile dementia of the Alzheimer type><specific biomarkers><surgery><tau phosphorylation><tau posttranslational modification><tau-1><three dimensional><τ phosphorylation>