Abstract Details

Title Clinical and Molecular PET Imaging Markers of Primary Progressive Aphasia due to Likely Alzheimer's Disease Pathology

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-023

Objective To identify patients with primary progressive aphasia (PPA) due to likely Alzheimer’s disease (AD) using digit span forward combined with amyloid- and tau-PET in regions associated with logopenic variant PPA (lvPPA).

Background PPA is associated with either AD or frontotemporal lobar degeneration (FTLD) neuropathology. PPA due to AD neuropathology is often associated with lvPPA. Impaired phonological loop function is observed in lvPPA, and digit span forward is a potential clinical marker of PPA due to AD neuropathology.

Design/Methods 14 PPA patients (9 lvPPA, 3 naPPA, 2 svPPA), diagnosed according to published criteria, were classified using an autopsy-validated CSF t-tau/a-beta ratio cut-off > 0.34 as having likely AD (10 patients: 9 lvPPA, 1 naPPA) or likely FTLD (4 patients: 2 naPPA, 2 svPPA) pathology. We obtained T1-weighted structural 3T MRI, ¹⁸F-florbetaben amyloid-PET, ¹⁸F-flortaucipir tau-PET, and the digit span forward task.¹⁸F-florbetaben and ¹⁸F-flortaucipir standardized uptake value ratios (SUVRs) were calculated using a cerebellar reference region excluding the dentate and fastigial nuclei, and mean SUVRs were calculated for an lvPPA region-of-interest (ROI) including left posterior superior temporal, middle temporal, and angular gyri.

Results Receiver operating characteristic analyses revealed that, consistent with existing literature, ¹⁸F-florbetaben mean SUVR in the lvPPA ROI was convergent with AD CSF biomarkers (100% sensitivity, 100% specificity, area under the curve (AUC)=1.00). Digit span forward was sensitive (90%) but not specific (50%) to likely AD pathology (AUC=0.94); one likely-AD lvPPA patient and two likely-FTLD patients (1 naPPA, 1 svPPA) were misclassified. ¹⁸F-flortaucipir improved specificity (90% sensitivity, 100% specificity, AUC=0.95); only the likely-AD naPPA patient was misclassified.

Conclusions In PPA, digit span forward is an inexpensive screening clinical marker sensitive to likely AD pathology, and amyloid- and tau-PET imaging improve specificity.

Authors/Disclosures
Emily Roll PRESENTER	No disclosure on file
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.
Molly B. Ungrady (Penn Frontotemporal Degeneration Center)	No disclosure on file
	No disclosure on file
	No disclosure on file
	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.
Ilya Nasrallah, MD, PhD	Dr. Nasrallah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Nasrallah has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Nasrallah has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Nasrallah has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Cassiday Schade LLP. The institution of Dr. Nasrallah has received research support from NIH. The institution of Dr. Nasrallah has received research support from ASNR.
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. The institution of Dr. Irwin has received research support from Cervo Med.
Jeffrey S. Phillips, PhD (Penn FTD Center, Department of Neurology)	No disclosure on file

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