数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
研究问题
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized primarily by progressive cognitive impairment.
方法
Inclusion criteria were: (1) at least two follow-up visits; (2) complete information on age and APOE ε4 genotype; and (3) at least one measurement of the six target biomarkers (amyloid PET, CSF p-tau, hippocampal volume, cingulate volume, thalamic volume, ADAS-Cog13).；The three MRI structural markers (hippocampal volume, cingulate volume, and thalamic volume) were available for all 1,576 participants, providing complete foundational data for SuStaIn subtyping.；All 11 MRI-based volumetric features required for SuStaIn subtyping were available for all participants included in this study.；After applying the above inclusion and exclusion criteria, a total of 1,576 participants were included in the longitudinal analysis.
核心结论
Age (F = 13.42, p < 0.001), sex (χ2 = 20.79, p < 0.001), and APOE ε4 carrier status (χ2 = 23.61, p < 0.001) all differed significantly across subtypes, whereas the number of follow-up visits did not (F = 1.07, p = 0.343).；Subtype 3 was the oldest (mean 73.3 years) and had the highest proportion of males (59.6%) and APOE ε4 carriers (52.1%), while Subtype 2 was the youngest (mean 70.7 years) and had the lowest APOE ε4 carrier rate (36.8%).；Subtype 3 had the oldest age (mean 73.3 years), the highest proportion of males (59.6%), and the highest APOE ε4 carrier rate (52.1%). ‖ 结论：These findings suggest that subtype-specific considerations should be incorporated into clinical trial design and risk stratification to improve statistical power and targeting of interventions.
局限
Similarly, Estarellas et al. developed a missing-data-enabled multimodal SuStaIn extension, integrating structural MRI, amyloid PET, tau PET, and CSF biomarkers to reveal five subtypes that capture both spatial and pathological heterogeneity (Estarellas et al., 2024).；However, given the subtle differences between Subtype 1 and Subtype 2 in hippocampal trajectories, the ‘hippocampus-sparing’ label should be interpreted with caution.；The association of APOE ε4 with biomarker trajectories showed significant heterogeneity across subtypes.
对本项目的价值
★★★☆☆ 脑老化是最大未满足需求，也是终点最难量化的领域；biomarker 与认知读数选择最敏感。队列：ADNI；最大样本量约 1,576；设计 横断面、观察性。
全文来源
PMC JATS 全文（正文 39,747 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Heterogeneous progression of AT(N) biomarkers in data-driven subtypes of Alzheimer's disease.
- 期刊与标识：Front Aging Neurosci · PMID 42948157 · DOI 10.3389/fnagi.2026.1902282**
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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