在A4和LEARN研究中,认知衰退的潜在类别不同
medRxiv : the preprint server for health sciences
|December 25, 2025
概括
具有阿尔茨海默病生物标志物的认知正常人表现出不同的认知衰退率. 识别这些子组,如稳定,缓慢或快速下降者,对于预测进展和开发向阿尔茨海默症患者至关重要.
科学领域:
- 神经学 神经学
- 生物标志物 生物标志物
- 认知科学 认知科学
背景情况:
- 在没有认知障碍的个体中,阿尔茨海默病 (AD) 生物标志物预测衰退,但进展时间和速度的异质性不明.
- 描述这种异质性对于理解临床前阿尔茨海默病和设计有效干预措施至关重要.
研究的目的:
- 在具有AD生物标志物的认知正常个体中识别认知衰退的不同子组.
- 确定临床前AD进展中异质性的基线预测因素.
主要方法:
- 分析了A4研究 (粉样蛋白阳性) 和LEARN研究 (粉样蛋白阴性) 的纵向数据.
- 参与者接受了基线的粉样蛋白PET,血P-tau217,MRI和认知评估.
- 隐性类混合效应模型 (LCMMs) 确定了认知轨迹类.
主要成果:
- 三种不同的认知轨迹类别出现了:稳定,缓慢下降和快速下降.
- 较高的血P-tau217,较小的海马体积和高的tau PET与认知能力下降的几率增加有关.
- 大约70%的粉样蛋白阳性参与者在随访期间保持稳定.
结论:
- 潜阶级建模揭示了临床前AD认知轨迹的显著异质性,即使存在AD病理.
- 稳定个体的很大比例表明长期的临床前阶段.
- 识别衰退子组可以增强预后模型,并为二次预防试验的丰富策略提供信息.
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