Author Identifier (ORCID)

Simon M. Laws: https://orcid.org/0000-0002-4355-7082

Abstract

Introduction : Emergent Alzheimer's disease (AD) represents a transitional stage where cognitively unimpaired (CU) individuals exhibit subthreshold but increasing amyloid-β (Aβ) levels. The impact of Aβ accumulation on brain volume loss and cognition during this early stage remains unclear. Methods: This retrospective cohort study analyzed data from 408 CU participants who were initially Aβ− (< 15 Centiloids) and followed for up to 15 years. Changes in basal forebrain and hippocampal volume, along with domain-specific cognitive performance, were compared between those who progressed to Aβ+ (≥20 Centiloids) and those who remained Aβ−. Results: Sixty-five CU participants progressed to Aβ+, indicating emergent AD, and showed faster Aβ accumulation and subtle memory decline. However, no significant differences in rate of BF and hippocampal atrophy were observed between groups. Discussion: The results suggest that during this emergent phase of AD, Aβ accumulation is associated with episodic memory loss, in the absence of detectable accelerated brain atrophy. Highlights: Identified cognitively unimpaired individuals in the emergent stage of Alzheimer's disease (AD). Emergent AD exhibits a greater rate of amyloid-β (Aβ) accumulation. No accelerated volume loss detected in the basal forebrain or hippocampus. Emergent AD is also associated with a subtle decline in memory. Early Aβ accumulation may impair cognitive function before structural atrophy.

Document Type

Journal Article

Date of Publication

7-1-2025

Volume

17

Issue

3

Publication Title

Alzheimer's and Dementia Diagnosis Assessment and Disease Monitoring

Publisher

Wiley

School

Centre for Precision Health / School of Medical and Health Sciences

RAS ID

83696

Funders

Alzheimer's Association / Alzheimer's Drug Discovery Foundation / Anonymous Foundation / Science and Industry Endowment Fund / Dementia Collaborative Research Centres / Victorian Government's Operational Infrastructure Support Program / Australian Alzheimer's Research Foundation / National Health and Medical Research Council / Yulgilbar Foundation

Grant Number

NHMRC Numbers : GNT2009550, GNT2019129

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Comments

Xia, Y., Bourgeat, P., Doré, V., Fripp, J., Lim, Y. Y., Laws, S. M., Fowler, C., Rowe, C. C., Masters, C. L., Coulson, E. J., & Maruff, P. (2025). Amyloid accumulation, brain atrophy, and cognitive decline in emergent Alzheimer’s disease. Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring, 17(3). https://doi.org/10.1002/dad2.70155

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Link to publisher version (DOI)

10.1002/dad2.70155