Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults

Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloidb plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions. This study of cognitively unimpaired older individuals examined whether serial position scores in word-list recall cross-sectionally predicted tau PET load in the MTL, and were able to discriminate between biomarker profiles, based on AT classification. Methods: Data from 490 participants (mean age 1 / 4 68.8 +/- 7.2) were extracted from two cohorts, which were merged into one sample. Linear regression analyses were carried out with regional volume-controlled tau (18F-MK-6240) PET SUVR of the entorhinal cortex (EC), parahippocampal cortex (PHC) and hippocampus (H) as outcomes, cross-sectional memory scores from the Rey Auditory Verbal Learning Test as predictors (total and delayed recall, along with serial position scores) and control variables, in separate analyses for each outcome and predictor. The sample was then stratified by biomarker profile and ANCOVAs were conducted with the strongest scores from the regression analyses, AT groups as fixed factor and the covariates. Results: Higher delayed primacy significantly predicted lower tau PET in EC, PHC, and H, cross-sectionally. Higher total recall scores predicted lower EC tau, but delayed primacy showed the best model fit, as indicated by AICs. ANCOVAs showed that AVLT metrics did not significantly discriminate between A-T- and A+T+, after correcting for multiple comparisons. Conclusions: Serial position analysis of word-list recall, particularly delayed primacy, may be a valuable tool for identifying in vivo tau pathology in cognitively unimpaired individuals. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).