Abstract Details

Title Association Between Preoperative Delirium and Plasma Biomarkers of Neuropathology Following Acute Hip Fracture: Hip Fracture Inpatient Pathophysiology Study (HIPS) Pilot

Topic Neurohospitalist

Presentation(s) P8 - Poster Session 8 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-002

Objective To investigate the association between preoperative delirium and plasma neuropathology biomarkers.

Background Delirium is common in older adults but its association with neuropathology biomarkers in the emergent preoperative setting is less understood.

Design/Methods Adults age 65+ hospitalized <72hr after acute hip fracture underwent delirium screening (Confusion Assessment Method) and preoperative blood collection. Plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated tau (P-tau217) were measured via Quanterix kits on Simoa HD-X. Cognitive status was determined by preexisting diagnosis and Informant Questionnaire for Cognitive Decline in the Elderly. Descriptive statistics utilized chi-square or Wilcoxon rank-sum. Linear regression explored the association between delirium and biomarkers on preoperative enrollment day.

Results

Of 16 subjects (ongoing enrollment N=31): mean age 82 years (IQR 73-84), 81% women, 38% had dementia, 50% had delirium preoperatively. 31% reported headstrike with hip fracture; no intracranial pathology on CT. Those with delirium (vs without) had increased prevalence of dementia (80% vs. 18%, p=0.02). Those with delirium (vs without) had higher median NfL [154pg/mL (IQR 31-323) vs 20pg/mL (IQR 17-28), p<0.01], higher median P-tau217 [0.22pg/mL (IQR 0.20-0.31) vs 0.08pg/mL (IQR 0.04-0.12), p=0.01], and trend towards higher median GFAP [352pg/mL (IQR 178-410) vs 215pg/mL (IQR 95-259), p=0.27]. No differences were found in age, sex, or headstrike in those with delirium vs. without. In univariable regressions, NfL was significantly associated with delirium, as was P-tau217. In multivariable regressions adjusting for age and dementia, NfL remained independently associated with delirium (coeff 194pg/mL, 95% CI 74-315, p=0.004); P-tau217 also remained independently associated with delirium (coeff 0.15, 95%CI 0.04-0.27, p=0.01).

Conclusions In older adults admitted for emergent hip fracture, preoperative delirium was independently associated with elevated NfL and P-tau217 before surgery, even after controlling for history of dementia. Our findings raise questions about the pathophysiology and time-course of neuronal injury in delirium.

Authors/Disclosures
Sara LaHue, MD PRESENTER	The institution of Dr. LaHue has received research support from National Institute on Aging . The institution of Dr. LaHue has received research support from Larry L. Hillblom Foundation . The institution of Dr. LaHue has received research support from UCSF Claude D. Pepper Older Americans Independence Center . The institution of Dr. LaHue has received research support from UCSF Bakar Aging Research Institute. The institution of Dr. LaHue has received research support from Doris Duke Foundation . The institution of Dr. LaHue has received research support from National Institute on Aging . The institution of Dr. LaHue has received research support from Longevity Impetus Grants. Dr. LaHue has received publishing royalties from a publication relating to health care.
Ketura Berry, MD (UCSF)	Dr. Berry has nothing to disclose.
Joy Youn	Miss Youn has nothing to disclose.
Julio C. Rojas-Martinez, MD, PhD (UCSF)	Dr. Rojas-Martinez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ferrer International, S.A.. The institution of Dr. Rojas-Martinez has received research support from NIH/NIA. The institution of Dr. Rojas-Martinez has received research support from Eli Lilly. The institution of Dr. Rojas-Martinez has received research support from Eisai. The institution of Dr. Rojas-Martinez has received research support from Amylyx.
Lawren VandeVrede, MD, PhD (UCSF)	Dr. VandeVrede has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. VandeVrede has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. VandeVrede has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CND Life Sciences. Dr. VandeVrede has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Siemens. Dr. VandeVrede has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. VandeVrede has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Peerview CME. Dr. VandeVrede has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Haymarket. Dr. VandeVrede has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Peter Lacques, LLC. Dr. VandeVrede has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cunningham Bounds. The institution of Dr. VandeVrede has received research support from Alzheimer's Association. The institution of Dr. VandeVrede has received research support from NIH.
David Castro (UCSF)	David Castro has nothing to disclose.
Stephanie Roa Diaz	No disclosure on file
Thelma Garcia (Buck Institute for Research on Aging)	No disclosure on file
Nida Degesys (UCSF)	No disclosure on file
John Boscardin	No disclosure on file
Kenneth Covinsky	No disclosure on file
Stephanie Rogers	Stephanie Rogers has a non-compensated relationship as a Faculty consultant with IHI that is relevant to AAN interests or activities.
John Newman (Buck Institute for Research on Aging)	John Newman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Junevity. John Newman has or had stock in BHB Therapeutics.John Newman has or had stock in Selah Therapeutics.John Newman has or had stock in BOPZ. The institution of John Newman has received research support from NIH. The institution of John Newman has received research support from Hevolution Foundation. The institution of John Newman has received research support from ARPA-H. The institution of John Newman has received research support from US Department of Defense. The institution of an immediate family member of John Newman has received research support from The Fibrolamellar Cancer Foundation. John Newman has received intellectual property interests from a discovery or technology relating to health care. John Newman has received intellectual property interests from a discovery or technology relating to health care. John Newman has received intellectual property interests from a discovery or technology relating to health care. John Newman has received publishing royalties from a publication relating to health care. An immediate family member of John Newman has received personal compensation in the range of $500-$4,999 for serving as a Committee Voting Member with NIH. John Newman has received personal compensation in the range of $0-$499 for serving as a Peer Reviewer with NIH. John Newman has received personal compensation in the range of $500-$4,999 for serving as a DSMB Member with NIH.
Bruce L. Miller, MD, FAAN (University of California, San Francisco)	Dr. Miller has nothing to disclose.
Adam L. Boxer, MD, PhD (University of California, San Francisco)	An immediate family member of Dr. Boxer has received personal compensation for serving as an employee of Kaiser Permanente. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Oscotec. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Switch. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alector. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Transposon. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Boxer has stock in Alector. Dr. Boxer has stock in Arvinas. Dr. Boxer has stock in Neurovanda. The institution of Dr. Boxer has received research support from Biogen. The institution of Dr. Boxer has received research support from Eisai. The institution of Dr. Boxer has received research support from Regeneron. The institution of Dr. Boxer has received research support from NIH. The institution of Dr. Boxer has received research support from Bluefield Project-5. Dr. Boxer has received research support from Rainwater Charitable Foundation. Dr. Boxer has received research support from GHR Foundation. Dr. Boxer has received intellectual property interests from a discovery or technology relating to health care.
Vanja C. Douglas, MD, FAAN (Univ of California, San Francisco)	Dr. Douglas has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Various legal firms. Dr. Douglas has received publishing royalties from a publication relating to health care. Dr. Douglas has received publishing royalties from a publication relating to health care.

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