Primacy and recency effects in verbal memory are differentially associated with post‐mortem frontal cortex p‐tau217 level in a mixed sample of community‐dwelling older adults

Abstract

AbstractBackgroundEmerging research indicates plasma phosphorylated (p)‐tau217 levels may demonstrate sensitivity to preclinical and symptomatic Alzheimer’s disease (AD). Serial position effects (primacy and recency) in verbal memory are sensitive cognitive markers of early AD; however associations between these measures and p‐tau217 in postmortem brain samples are unclear. In a mixed sample of older adults, this study examined how primacy and recency scores measured years before death are associated with post‐mortem levels of p‐tau217, with p‐tau202 as a complementary post‐mortem measure of early tau phosphorylation.MethodData were used from the Rush University Religious Orders Study and the Memory and Aging Project. Participants were 1098 community‐dwelling older adults (68.9% female, M age = 80.1) who were non‐demented at baseline and followed until death (M follow‐up years = 9.2; status at death: 34.7% unimpaired, 26.0% mild cognitive impairment, 39.3% dementia). Baseline serial position scores were calculated as the proportion of words recalled from the beginning (primacy) and end (recency) of the CERAD Word Memory List. A neuropathological exam classified Braak stage. A middle frontal gyrus tissue sample was used to quantify p‐tau217 and p‐tau202 with selected reaction monitoring proteomics. Linear regression analyses examined associations of cognitive scores with p‐tau, adjusting for age, sex, education, APOE e4 status, Braak stage, and time to death.ResultAs expected, higher Braak scores were associated with higher levels of brain p‐tau217. In the fully adjusted model, higher baseline primacy scores (b = ‐.27, p = .026), but not recency scores (b = ‐.02, p = .901), were associated with lower levels of p‐tau217 but not p‐tau202 in middle frontal cortex. Higher delayed recall (b = ‐.08, p = .007), but not immediate recall (b = ‐.01, p = .071), was also associated with lower p‐tau217.ConclusionPrimacy scores measured years before death were associated with the outcome of post‐mortem brain levels of p‐tau217, but not p‐tau202. The differential associations of serial position scores with p‐tau suggest they may add complementary information about early neuropathological changes when used in conjunction with routine delayed recall scores. These findings further contribute to evidence for p‐tau217 as a sensitive biomarker of AD.