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Abstract Details

Diagnostic Applications of Cerebrospinal Fluid Biomarkers in Patients with Rapidly Progressive Dementia
Aging, Dementia, and Behavioral Neurology
P6 - Poster Session 6 (8:00 AM-9:00 AM)
9-003
Apply established and emerging cerebrospinal fluid (CSF) biomarkers to improve diagnostic accuracy and recognition of patients with potentially treatment-responsive causes of rapidly progressive dementia (RPD). 

Overlap in clinical presentation and results of diagnostic tests confounds etiologic diagnosis in patients with RPD. Objective measures are needed to improve diagnostic accuracy and to recognize patients with potentially treatment-responsive causes of RPD.

Patients with RPD were enrolled and evaluated from 2016-2022 in inpatient and outpatient clinics at two tertiary care centers; CSF was obtained following the initial presentation and banked for research purposes. Biomarkers of Alzheimer disease neuropathology (Aβ42/40, p-tau181, p-tau231), neuroaxonal/neuronal injury (NfL, VILIP-1, total tau), neuroinflammation (YKL-40, sTREM2, GFAP, MCP-1), and synaptic dysfunction (SNAP-25, neurogranin) were measured in CSF from 78 prospectively accrued patients with RPD due to neurodegenerative, vascular, and autoimmune/inflammatory diseases; 35 age- and sex- matched patients with typical progressive neurodegenerative disease; and 72 cognitively normal controls. Biomarker levels were compared across etiologic diagnoses, by treatment responsiveness, and between patients with typical and rapid progressive presentations of neurodegenerative disease.
Alzheimer disease biomarkers associated with neurodegenerative causes of RPD. High NfL, sTREM2, YKL-40, and low VILIP-1 identified patients with autoimmune/inflammatory diseases. MCP-1 levels were highest in patients with vascular causes of RPD. A multivariate model including GFAP, MCP-1, p-tau181, and sTREM2 identified the 44 patients with treatment-responsive causes of RPD with 89% accuracy. Minimal biomarker differences were observed between patients with typical and rapidly progressive presentations of neurodegenerative disease.
Selected biomarkers associated with etiologic diagnoses and treatment responsiveness in patients with heterogeneous causes of RPD but did not inform the mechanisms that drive rapid progressive neurodegeneration. Biomarker panels may be adapted to improve etiologic diagnoses of RPD and recognition of patients with treatment-responsive causes of RPD early in the symptomatic course when diagnostic uncertainty and potential therapeutic responsiveness are highest.
Authors/Disclosures
Gregory S. Day, MD, MSc, FAAN (Mayo Clinic)
PRESENTER 		Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has or had stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Amgen Pharmaceuticals. The institution of Dr. Day has received research support from AVID Radiopharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with 好色先生. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing 好色先生, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Ionis Pharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a 好色先生al Case Development + Presentation (video) with PeerDirect (P\S\L Group). Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development / Presentation (non-CME) with MJH Life Sciences (NeurologyLive). Dr. Day has a non-compensated relationship as a Clinical Director with Anti-NMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.
Lindsey Kuchenbecker Lindsey Kuchenbecker has nothing to disclose.
Philip W. Tipton, MD Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Alzheimer's Tennessee. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Charlotte County Medical Society, Inc.
Yuka Martens (Mayo Clinic) No disclosure on file
Matthew Brier, MD, PhD (Washington University) Dr. Brier has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Brier has received research support from NIH.
Nihal Satyadev, MD, MPH (Mayo Clinic) Dr. Satyadev has nothing to disclose.
Steven R. Dunham, Jr., MD Dr. Dunham has nothing to disclose.
Evelyn Lazar, MD (JFK Medical Center) Dr. Lazar has nothing to disclose.
Maxwell Dacquel No disclosure on file
Rachel Henson (Washington University in St. Louis) No disclosure on file
Guojun Bu No disclosure on file
Michael D. Geschwind, MD, PhD, FAAN (UCSF) Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Brainstorm Cell Therapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Walter Grubb. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lehrman Group. Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Reata Pharmaceuticals, Inc..
John C. Morris, MD, FAAN (Washington University) Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CBR International Advisory Board. Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cure Alzheimers Fund. Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LEADS Steering Commitee. The institution of Dr. Morris has received research support from NIH grants. Dr. Morris has received intellectual property interests from a discovery or technology relating to health care. Dr. Morris has received intellectual property interests from a discovery or technology relating to health care.
Suzanne E. Schindler, MD, PhD (Washington University) Dr. Schindler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Schindler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Schindler has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novo Nordisk. The institution of Dr. Schindler has received research support from National Institute on Aging. Dr. Schindler has received personal compensation in the range of $0-$499 for serving as a Member of the Biospecimen Review Committee with National Centralized Repository for Alzheimer Disease. Dr. Schindler has a non-compensated relationship as a Board Member with Greater Missouri Alzheimer's Association that is relevant to AAN interests or activities.
Elizabeth Herries No disclosure on file
Neill R. Graff-Radford, MD, FAAN (Mayo Clinic Jacksonville) The institution of Dr. Graff-Radford has received research support from Biogen. The institution of Dr. Graff-Radford has received research support from Lilly. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Biogen. Dr. Graff-Radford has received publishing royalties from a publication relating to health care.