Wuestefeld Anika, Xie Long, McGrew Emily, Pichet-Binette Alexa, Spotorno Nicola, van Westen Danielle, Mattsson-Carlgren Niklas, Yushkevich Paul A, Das Sandhitsu R, Wolk David A, Wisse Laura E M
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Penn Image Computing and Science Laboratory (PICSL), University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alzheimers Dement. 2025 Jul;21(7):e70511. doi: 10.1002/alz.70511.
A granular understanding of the mechanisms linking tau pathology to cognitive decline in Alzheimer's disease is crucial. We investigate mediating effects of medial temporal lobe (MTL) and neocortical neurodegeneration on tau-induced domain-specific cognitive impairment in amyloid-beta (Aβ) positive cognitively normal and impaired adults.
We assessed magnetic resonance imaging-derived MTL and neocortical volume/thickness and F-Flortaucipir positron emission tomography in 319 Aβ-positive individuals. Cognitive functions across six domains were isolated by adjusting for other cognitive measures.
MTL tau correlated with memory subdomains, neocortical tau with executive function, and both with semantic fluency. Specific structural measures partially mediated these tau-cognition associations: Brodmann area 35 mediated tau-immediate and tau-delayed recall, posterior hippocampus tau-recognition, and inferior temporal cortex tau-semantic fluency associations.
Our findings provide a nuanced understanding of region-specific macrostructural atrophy as one pathway of tau-induced cognitive changes, aligning with known tau spread patterns. Additionally, isolating cognitive functions is a promising approach for future research.
Medial temporal lobe tau was related to memory domains; neocortical tau to executive function. Both tau positron emission tomography measures were associated with semantic fluency. Specific regional atrophy partially mediated tau-induced cognitive changes. Other mechanistic links between tau and cognitive subdomains require investigation. Isolated cognitive domains should be explored as future avenues of research.
深入了解将tau病理与阿尔茨海默病认知衰退联系起来的机制至关重要。我们研究了内侧颞叶（MTL）和新皮质神经变性对淀粉样β蛋白（Aβ）阳性认知正常和受损成年人中tau诱导的特定领域认知障碍的中介作用。
我们评估了319名Aβ阳性个体的磁共振成像衍生的MTL和新皮质体积/厚度以及F-氟代托卡朋正电子发射断层扫描。通过调整其他认知测量指标来分离六个领域的认知功能。
MTL tau与记忆子领域相关，新皮质tau与执行功能相关，两者均与语义流畅性相关。特定的结构测量指标部分介导了这些tau与认知的关联：布罗德曼区35介导了tau即时和tau延迟回忆、海马后区tau识别以及颞下回tau语义流畅性关联。
我们的研究结果提供了对区域特异性宏观结构萎缩作为tau诱导认知变化的一种途径的细致理解，这与已知的tau传播模式一致。此外，分离认知功能是未来研究的一种有前景的方法。
内侧颞叶tau与记忆领域相关；新皮质tau与执行功能相关。两种tau正电子发射断层扫描测量指标均与语义流畅性相关。特定区域萎缩部分介导了tau诱导的认知变化。tau与认知子领域之间的其他机制联系需要进一步研究。应探索分离的认知领域作为未来的研究途径。
