Abstract Details

Title Tau Status Portends Different Baseline and Longitudinal Cognitive Performance in Amyloid- and Neurodegeneration-positive Mild Cognitive Impairment (MCI)

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S23 - Aging and Dementia: Biomarkers and Clinical Trials (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Objective To examine tau-mediated cognitive differences in amyloid-and-neurodegeneration-positive MCI

Background Per the Amyloid/Tau/Neurodegeneration (A/T/N) Alzheimer’s-Disease (AD) model, amyloid accumulates during preclinical AD, while tau and neurodegeneration accompany clinical onset. Amyloid-positivity places individuals on the “AD spectrum,” but doesn’t differentiate those with cognitive decline and neurodegeneration due to non-AD pathology [e.g. LATE, cerebrovascular disease (CVD)]. “A+T-N+ MCI” could represent a biomarker-signature of concomitant AD- and non-AD pathology, wherein symptoms are driven by the latter, given tau-negativity, and thus may differ from A+T+N+ MCI.

Design/Methods A+N+ MCI participants with longitudinal cognitive data in ADNI2/ADNIGO were included. A/T and N status were determined by CSF and hippocampal volume, respectively. Immediate memory (IM), episodic memory (EM), category fluency (CF), naming, and executive function (EF) were assessed using AVTOT1, AVTOT6, animal-naming, the Boston Naming Test, and Trails-B-minus-A, respectively. 43 A+T-N+ MCI and 77 A+T+N+ MCI participants were compared at baseline, using (n=161) amyloid-negative-healthy-control-referenced Z-scores, and longitudinally, using age-, sex-, and education-adjusted mixed-effects models incorporating 1-4 years of follow-up.

Results Compared to A+T+N+ MCI, A+T-N+ MCI was less impaired on EM, CF, and naming at baseline (p<0.05), but similarly impaired on IM and EF. Compared to controls, A+T-N+ MCI had worse baseline performance on all domains except naming (p<0.01). Mixed-effects models comparing MCI groups showed significant time-group interactions for IM, EM, CF, and EF (p<0.05), reflecting faster decline in A+T+N+ MCI. Compared to 152 longitudinally-followed controls, A+T-N+ MCI exhibited significant time-group interactions for naming only (p<0.001), while A+T+N+ MCI declined faster on all domains (p<0.01).

Conclusions The finding that A+T-N+ MCI had disproportionate frontal network impairment (IM, EF), relative to typical-AD domains (EM, CF), suggests a less-AD-like baseline phenotype. Further, except in naming, A+T-N+ MCI did not decline faster than controls, suggesting that, in A+N+ MCI, tau-negativity portends a more indolent cognitive syndrome, possibly driven by non-AD pathologies (e.g. LATE, CVD).

Authors/Disclosures
Lauren McCollum, MD (Pat Summitt Clinic) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
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.

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