Primacy and recency effects in verbal memory are differentially associated with post-mortem frontal cortex p-tau 217 and 202 levels in a mixed sample of community-dwelling older adults

ABSTRACT

Introduction

Serial position effects in verbal memory are associated with in vivo fluid biomarkers and neuropathological outcomes in Alzheimer’s disease (AD). To extend the biomarker literature, associations between serial position scores and postmortem levels of brain phosphorylated tau (p-tau) were examined, in the context of Braak stage of neurofibrillary tangle progression.

Method

Participants were 1091 community-dwelling adults (M_age = 80.2, 68.9% female) from the Rush University Religious Orders Study and Memory and Aging Project who were non-demented at enrollment and followed for a mean of 9.2 years until death. The CERAD Word List Memory test administered at baseline and within 1 year of death was used to calculate serial position (primacy, recency) and total recall scores. Proteomic analyses quantified p-tau 217 and 202 from dorsolateral prefrontal cortex samples. Linear regressions assessed associations between cognitive scores and p-tau with Braak stage as a moderator.

Results

Cognitive status proximal to death indicated 34.7% were unimpaired, 26.2% met criteria for MCI, and 39.0% for dementia. Better baseline primacy recall, but not recency recall, was associated with lower p-tau 217 levels across Braak stages. Delayed recall showed a similar pattern as primacy. There was no main effect of immediate recall, but an interaction with Braak stages indicated a negative association with p-tau 217 level only in Braak V–VI. Within 1 year of death, there were no main effects for cognitive scores; however, recency, immediate and delayed recall scores interacted with Braak stage showing better recall was associated with lower p-tau 217 only in Braak V–VI. No associations were observed with p-tau 202.

Conclusions

Primacy recall measured in non-demented adults may be sensitive to emergent tau phosphorylation that occurs in the earliest stages of AD. Serial position scores may complement the routinely used delayed recall score and p-tau biomarkers to detect preclinical AD.

KEYWORDS:

• Verbal memory
• serial position
• biomarkers
• phosphorylated tau
• Alzheimer’s disease

Acknowledgments

We would like to thank the ROSMAP participants, as well as the research staff and investigators for their support of these two studies.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13803395.2023.2232583

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data Availability Statement

ROSMAP data can be requested at https://www.radc.rush.edu.

Additional information

Funding

ROSMAP are supported by funding from the National Institutes of Health under grants P30AG10161; P30AG72975; R01AG15819; and R01AG17917.