Abstract Details

Title A/T/N Criteria are Inconsistent in Autopsy-Confirmed Non-Amnestic Alzheimer’s Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S34 - Aging and Dementia: Risk Factors, Biomarkers, and Neuropathology (2:17 PM-2:28 PM)

Poster/Presentation
Number 008

Background The A/T/N scheme proposes biomarker and imaging criteria for high-confidence diagnosis of AD. However, the sensitivity of these criteria for diagnosing naAD is currently unclear.

Objective To evaluate recent amyloid/tau/neurodegeneration (A/T/N) diagnostic criteria for Alzheimer's disease (AD) in non-amnestic AD (naAD).

Design/Methods We studied 39 patients (19 non-amnestic, 20 amnestic) with autopsy-confirmed AD. All patients had structural MRI and cerebrospinal fluid (CSF) measures of Aβ_1–42 and phosphorylated tau (p-tau₁₈₁). MRI data were compared with 37 matched controls. CSF Aβ_1–42 and p-tau₁₈₁ levels were quantified with the Luminex platform, and positivity was based on validated thresholds (Aβ_1–42≤192 pg/ml; p-tau₁₈₁>23 pg/ml). Neurodegeneration was assessed by a z-score less than -1.0 relative to controls. We compared multiple markers of neurodegeneration, including hippocampal volume and mean cortical thickness.

Results Age at CSF was lower for naAD patients (median=59.7, Q1=57.5, Q3=68.7; p<0.02) than for aAD (median=72.6, interquartile range [IQR]=61.8–77.2); disease duration did not differ (median=3.4, IQR=2.2–5.1). CSF Aβ_1–42 levels did not differ between naAD (mean=138.5 pg/mL, SD=49.3) and aAD (mean=152.2 pg/mL, SD=49.1; p>0.4); however, p-tau levels were lower for naAD (22.9 pg/mL, SD=11.0) than aAD patients (45.7 pg/mL, SD=32.2; p<0.01) with or without adjustment for age and disease duration. Mean cortical thickness was more sensitive to neurodegeneration in naAD than hippocampal volume (81% vs. 56%). Overall, 66.7% of aAD patients but only 43.8% of naAD patients were positive for markers of Aβ_1–42, p-tau, and neurodegeneration.

Conclusions A/T/N criteria were less reliable in autopsy-confirmed patients with naAD, primarily due to lower p-tau levels among naAD than aAD, and hippocampal volume was a less effective marker of neurodegeneration than mean cortical thickness in naAD.

Authors/Disclosures
Jeffrey S. Phillips, PhD (Penn FTD Center, Department of Neurology) PRESENTER	No disclosure on file
David Irwin, MD (University of Pennsylvania)	The institution of Dr. Irwin has received research support from NIH. The institution of Dr. Irwin has received research support from Prevail. The institution of Dr. Irwin has received research support from Passage Bio. The institution of Dr. Irwin has received research support from Alector. The institution of Dr. Irwin has received research support from Transposon. The institution of Dr. Irwin has received research support from Denali.
Emily Roll	No disclosure on file
Corey McMillan, PhD (University of Pennsylvania)	Dr. McMillan has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. McMillan has received research support from Biogen. The institution of Dr. McMillan has received research support from NIH.
	No disclosure on file
	No disclosure on file
Leslie M. Shaw, PhD (Perelman School of Med, U of PA)	Dr. Shaw has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Shaw has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Shaw has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Shaw has received research support from NIA. The institution of Dr. Shaw has received research support from MJ Fox foundation for Parkinsons Research.
John Q. Trojanowski, MD, PhD (University of PA School of Med)	Dr. Trojanowski has nothing to disclose.
David A. Wolk, MD, FAAN (University of Pennsylvania)	Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. The institution of Dr. Wolk has received research support from Biogen. Dr. Wolk has received publishing royalties from a publication relating to health care. Dr. Wolk has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Eli Lilly.
Murray Grossman, MD, FAAN (University of Pennsylvania)	Dr. Grossman has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. The institution of Dr. Grossman has received research support from NIH.

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