Department of Neuroscience, University of California Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Department of Neuroscience, University of California Berkeley, Berkeley, CA 94720, USA.
Neurobiol Aging. 2025 Jan;145:32-41. doi: 10.1016/j.neurobiolaging.2024.10.004. Epub 2024 Oct 19.
The early accumulation of AD pathology such as Aβ and tau in cognitively normal older people is predictive of cognitive decline, but it has been difficult to dissociate the cognitive effects of these two proteins. Early Aβ and tau target distinct brain regions that have different functional roles. Here, we assessed specific longitudinal pathology-cognition associations in seventy-six cognitively normal older adults from the Berkeley Aging Cohort Study who underwent longitudinal PiB PET, FTP PET, and cognitive assessments. Using linear mixed-effects models to estimate longitudinal changes and residual approach to characterizing cognitive domain-specific associations, we found that Aβ accumulation, especially in frontal/parietal regions, was associated with faster decline in executive function, not memory, whereas tau accumulation, especially in left entorhinal/parahippocampal regions, was associated with faster decline in memory, not executive function, supporting an "Aβ-executive function, tau-memory" double-dissociation in cognitively normal older people. These specific relationships between accumulating pathology and domain-specific cognitive decline may be due to the particular vulnerabilities of the frontal-parietal executive network to Aβ and temporal memory network to tau.
AD 病理学（如 Aβ 和 tau）在认知正常的老年人中的早期积累可预测认知能力下降，但很难区分这两种蛋白质的认知效应。早期的 Aβ 和 tau 针对的是具有不同功能作用的不同大脑区域。在这里，我们评估了来自伯克利老龄化队列研究的 76 名认知正常的老年人的特定纵向病理学-认知关联，这些老年人接受了纵向 PiB PET、FTP PET 和认知评估。使用线性混合效应模型来估计纵向变化，并采用残差方法来描述认知领域特异性关联，我们发现 Aβ 积累，特别是在前额/顶叶区域，与执行功能的更快下降有关，而不是记忆，而 tau 积累，特别是在左侧内嗅/海马旁回区域，与记忆的更快下降有关，而不是执行功能，这支持认知正常老年人中“Aβ-执行功能，tau-记忆”的双重分离。这种积累的病理学与特定领域认知下降之间的特定关系可能是由于额叶-顶叶执行网络对 Aβ 和颞叶记忆网络对 tau 的特定脆弱性所致。
