Amyloid accumulation, brain atrophy, and cognitive decline in emergent Alzheimer's disease.

IF 4.4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-07-29 eCollection Date: 2025-07-01 DOI:10.1002/dad2.70155

Ying Xia, Pierrick Bourgeat, Vincent Doré, Jurgen Fripp, Yen Ying Lim, Simon M Laws, Christopher Fowler, Christopher C Rowe, Colin L Masters, Elizabeth J Coulson, Paul Maruff

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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.

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急性阿尔茨海默病的淀粉样蛋白积累、脑萎缩和认知能力下降。

简介：突发性阿尔茨海默病（AD）代表了一个过渡阶段，认知未受损（CU）个体表现出阈以下但淀粉样蛋白-β (a β)水平升高。在早期阶段，Aβ积累对脑容量损失和认知的影响尚不清楚。方法：本回顾性队列研究分析了408名最初为Aβ-的CU参与者的数据(结果：65名CU参与者进展为Aβ+，表明急性AD，并表现出更快的Aβ积累和轻微的记忆力下降。但两组间BF和海马萎缩率无显著差异。讨论：结果表明，在阿尔茨海默病的这个突发阶段，在没有可检测到的加速脑萎缩的情况下，Aβ积累与情景性记忆丧失有关。重点：在阿尔茨海默病（AD）的新兴阶段识别认知未受损个体。突发性AD表现出更高的淀粉样蛋白-β (a β)积累率。基底前脑和海马体未发现体积加速损失。突发性阿尔茨海默病还与记忆力的轻微下降有关。早期Aβ积累可能在结构萎缩前损害认知功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.