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.