Demirsoy Idris, Ghanbarian Elham, Khorsand Babak, Nallapu Bhargav T, Petersen Kellen K, Lipton Richard B, Sajjadi S Ahmad, Rabin Laura A, Ezzati Ali
Department of Neurology University of California, Irvine Irvine California USA.
Saul R. Korey Department of Neurology Albert Einstein College of Medicine Bronx New York USA.
Alzheimers Dement (Amst). 2025 Jun 18;17(2):e70128. doi: 10.1002/dad2.70128. eCollection 2025 Apr-Jun.
Alzheimer's disease (AD) has a long preclinical phase in which individuals may accumulate amyloid beta (Aβ) and tau pathology without noticeable cognitive impairment. Subjective cognitive impairment reports can provide early insights into cognitive decline.
In the A4 Study, 339 cognitively unimpaired, Aβ-positive individuals underwent tau positron emission tomography imaging. Tau status was classified based on medial temporal lobe tau standardized uptake value ratios (tau). Participants and study partners assessed cognitive changes using the 15-item Cognitive Function Index (CFI) questionnaire. We explored the relationship among tau, hippocampal volume (HVa), and CFI reports.
Higher tau was associated with participant-reported concerns about memory and navigation, and with study partner-reported difficulty remembering appointments. Lower HVa showed a marginal association with participant-reported driving difficulty.
These findings support the utility of participant- and study partner-reported concerns as early indicators of preclinical AD pathology, with potential value for early detection and trial enrichment strategies.
Higher tau in the medial temporal lobe (tau) was linked to participant-reported memory and orientation decline such as needing reminders or getting lost.Higher tau was associated with increased memory-related concerns, such as needing help with appointments and asking repetitive questions.Lower hippocampal volume was associated with spatial memory and navigation such as driving difficulties and greater memory decline as reported by study partners.
阿尔茨海默病（AD）有一个漫长的临床前期阶段，在此阶段个体可能会积累β淀粉样蛋白（Aβ）和tau蛋白病变，但无明显认知障碍。主观认知障碍报告可以为认知衰退提供早期见解。
在A4研究中，339名认知未受损、Aβ阳性个体接受了tau正电子发射断层扫描成像。根据内侧颞叶tau标准化摄取值比率（tau）对tau状态进行分类。参与者和研究伙伴使用15项认知功能指数（CFI）问卷评估认知变化。我们探讨了tau、海马体积（HVa）和CFI报告之间的关系。
较高的tau与参与者报告的对记忆和导航的担忧以及研究伙伴报告的难以记住预约有关。较低的HVa与参与者报告的驾驶困难有微弱关联。
这些发现支持了参与者和研究伙伴报告的担忧作为临床前期AD病理早期指标的效用，对早期检测和试验富集策略具有潜在价值。
内侧颞叶较高的tau（tau）与参与者报告的记忆和定向衰退有关，如需要提醒或迷路。较高的tau与增加的记忆相关担忧有关，如在预约方面需要帮助和反复提问。较低的海马体积与空间记忆和导航有关，如研究伙伴报告的驾驶困难和更大的记忆衰退。
