Delirium
Conditions
Brief summary
The IPOD-B3 study aims to characterize the relationship between premorbid brain activity and postoperative delirium in patients undergoing major surgery. This is a expansion of the NeuroVISION Bolt-On study, NCT01980511.
Interventions
PROCEDUREBlood specimen collection
Blood will be collected from participants
DIAGNOSTIC_TESTPupillometry
A pupillometer is a device that measures the size of the pupils.
PROCEDUREHigh Density-Electroencephalogram
EEG is a safe non-invasive technology without complications that may be used to help diagnose delirium
PROCEDUREMagnetic Resonance Imaging
MRI scan of brain
Sponsors
National Institute on Aging (NIA)
University of Wisconsin, Madison
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Cohort 1: Age ≥65 years * Cohort 2: Age ≥60 years * Anticipated length of hospital stay of at least 2 days after surgery that occurs under general or neuraxial anesthesia * Written Informed Consent for potential participation prior to surgery
Exclusion criteria
* Contraindication to EEG * Unable or unwilling to attend the follow-up appointments * Documented history of dementia * Deemed incapable of providing consent by surgical team * Residing in a nursing home * Undergoing intracranial surgery * Unable to complete neurocognitive testing due to language, vision or hearing impairment * Unable to communicate with the research staff due to language barriers * For optional MRI portion of the study: Contraindication to MRI (e.g., implanted devices not safe for MRI studies, claustrophobia, unable to lie flat or still)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Connectivity | Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Post-Operative days 1-4 | Change from baseline functional connectivity at immediate postoperative period and association between delirium (CAM) and functional connectivity of the cingulate cortex |
| Brain state change | Post-operative day 1 through 4 | Quantified by the MSD across regions of interest from resting state time-series to randomly spaced points across the time-series. Measured for Cohort 2 only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain measurements | Preoperative MRI will occur up to 4-weeks prior to surgery. Delirium is followed postoperatively, days 1-4 | Assess the association between preoperative white matter connectivity (DTI) and cortical thickness (derived from MRI) and postoperative delirium |
| Long term cognition | Pre-operative cognition measures will occur up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Long term post-operative cognition measured 1 year after surgery. | Examine the incidence of delirium with change in cognition from preoperatively to one-year postoperatively. |
| Baseline cognition, specific and global. | Cognition is assessed preoperatively. Participants are followed for delirium on postoperative days 1-4 | Examine the association between preoperative cognition using a neuropsychological battery, and postoperative delirium incidence. |
| Biomarkers and brain measurements | Pre-op measures: up to 4 weeks prior to surgery. Post-op measures: one year, and two years, after surgery. | Assess the changes in cognition and biomarkers over one year with EEG changes. |
| Representativeness of surgical population | Pre-op MRI: up to 4 weeks prior to surgery. | Identify whether patients who consent to the MRI are reflective of the surgical population. |
| Genetics and delirium | Pre-op blood collected up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Post-operative blood collected on postoperative days 1-4. Long term blood collected 90 days and 1 year after surgery. | Identify genetic and epigenetic changes associated with delirium and its pathogenesis. |
| Postoperative amyloid beta deposition and delirium | Post-operative delirium measured on postoperative days 1-4. PET imaging will occur 90 days after surgery. | Identify associations between delirium and amyloid beta deposition detected by Positron Emission Tomography at 90 days after surgery in sub-study IPOD-PET. |
| Long term changes in amyloid beta deposition and delirium | Pre-operative PET imaging will occur up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Post-operative PET imaging will occur 1 year after surgery. | Identify associations between delirium and amyloid beta deposition detected by Positron Emission Tomography preoperatively and 1 year after surgery in sub-study IPOD-PET2. |
| Mismatch negativity | Post-operative day 1 through 4 | EEG mismatch negativity during delirium compared to resolution of delirium. |
| Resolution of slow wave activity | Post-operative day 1 through 4 | Slow wave activity during delirium compared to resolution of delirium. |
| Inflammation | Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: POD1-4 | Assess the changes from preoperative to postoperative EEG associated with delirium and change in plasma/cerebrospinal fluid (CSF) IL-6 or other biomarkers (e.g. other cytokines or markers of neronal injury) |
| Effects of inflammation on brain activity | Post-operative day 1 through 4 | EEG correlations with biomarkers of inflammation and neuronal injury. |
| Delirium subtypes - neuronal dynamics | Post-operative day 1 through 4 | EEG neuronal dynamics (energy landscape analysis) during hyperactive vs hypoactive delirium. |
| Delirium subtypes - predisposing neuronal dynamics | Up to 4 weeks prior to surgery. | Preoperative neuronal dynamics between hyperactive and hypoactive delirium. |
| Delirium subtypes - network stitching | Post-operative day 1 through 4 | Task evoked network switching and locus coeruleus activity between hyperactive and hypoactive delirium. |
| Delirium subtypes - network integration | Up to 4 weeks prior to surgery. | Preoperative brain network integration vs differentiation between hyperactive and hypoactive delirium. |
| Pupillary responses | Post-operative day 1 through 4 | Pupillary response during rest and cognitive task in delirious versus nondelirious participants. |
| Metabolism and SWA | Post-operative day 1 through 4 | Correlation between SWA location, delirium subtype, and MCT2 expression. |
| Injury versus inflammation | 4 weeks prior to surgery to 1 year post-surgery | Delayed resolution of biomarkers of neuronal dysfunction and inflammation as competing theories to neuronal injury. |
| Neuronal injury - surgery type | Post-operative day 1 through 4 | Association between biomarkers of neuronal injury and type of surgery. |
| Change in cognition | Baseline to 1 year post-surgery | Association of biomarkers of neuronal injury with change in cognition at 1 year. |
| Connectivity during delirium | Post-operative day 1 through 4 | Dynamic causal modeling of cortical connectivity during delirium. |
| Biomarkers | Post-operative day 1 through 4 | Identify biomarkers of delirium and neural damage through changes in circulating plasma proteins and molecules (through mass spectometry) |
Countries
United States
Contacts
Primary ContactDavid Kunkel, BS
Backup ContactFrankie Ingram, BS
Outcome results
None listed