认知年老化中的补偿性重组机制：认知神经基础与干预研究

Challenging the traditional views of cognitive aging as purely passive decline, the proposed project aims to explain compensatory reorganization of cognitive aging from an active perspective of plasticity. Compensatory reorganization refers to the phenomenon which older adults recruit additional brain resources to compensate for their cognitive decline. The project will use cross-sectional design to track the occurrence and development of compensatory reorganization through the whole path of brain decline (younger adults, older adults, Mild Cognitive Impairment, Alzheimer’s disease). By adopting the techniques of multimodal neuroimaging, transcranial magnetic stimulation (TMS) and genotyping, the project will explore the underlying neural basis of compensatory reorganization and impacts of APOE genotype on the reorganization. TMS will be used to build a direct causal link between brain reorganization and compensation for cognitive decline. Further, the project will investigate whether cognitive training will induce enhancement in compensatory reorganization, or alternatively, restoration of impaired brain function in older adults.. We expect to find: (1) an inverted U relationship between compensatory reorganization and brain decline in whole-brain large scale functional and structural networks; (2) APOE ε2 associates with enhanced compensatory reorganization while ε4 associates with less reorganization; (3) TMS on brain regions of compensatory reorganization disturbs corresponding cognitive process; (4) cognitive training may enhance compensatory reorganization. The project will contribute to uncover the essence of brain and cognitive plasticity of aging and provide scientific evidence for postponing late-life cognitive deterioration and preventing neurodegenerative diseases.

区别于认为认知老化即是被动下降的传统观点，从积极可塑的视角理解认知老化过程中的补偿性重组机制（即老年人有可能动用额外的脑资源来补偿认知的下降）。采用横断行为研究结合多模态核磁共振成像、经颅磁刺激、基因分型等技术，探究补偿性重组在脑衰退全程（青年、老人、MCI、AD）中的变化规律、脑神经基础及APOE基因的影响，并尝试建立“重组”与“补偿”之间的因果联系。在此基础上，进一步探索认知训练是增强老年人脑功能的补偿性重组，还是有助于老年人恢复业已受损的脑功能。. 预期发现：补偿性重组与脑衰退程度呈倒U关系，并在全脑功能和结构的大尺度网络上有所体现；APOE ε2的保护作用和ε4的风险影响分别与补偿性重组的增强和减弱相关；TMS刺激重组脑区会影响对应的认知加工；认知训练可能增强补偿性重组。本研究有助于揭示脑老化和认知可塑性的本质，也会为延缓认知衰退、预防神经退行性疾病提供科学依据。

区别于认为认知老化即是被动下降的传统观点，从积极可塑的视角对认知老化过程中的补偿性重组机制（即老年人有可能动用额外的脑资源来补偿认知的下降）进行了深度探究。重点聚焦于解析了补偿性重组在脑衰退全程（从认知正常/NC到轻度认知损伤/MCI到痴呆老人/AD）中的变化规律。继而进一步探索无创脑刺激（经颅磁/rTMS和经颅电刺激/tDCS）是增强老年人脑功能的补偿性重组（即神经可塑性的量变），还是有助于老年人恢复业已受损的脑功能（即神经可塑性的质变）。. 结果发现轻度认知损伤阶段的个体可以通过补偿性重组来实现和认知正常老人相当的记忆成绩，随着病程加重到痴呆阶段，补偿性重组的能力明显衰退，认知成绩出现显著下降，提示补偿性重组与脑衰退程度呈倒U关系。通过系列研究发现无创性脑刺激干预能够老年人大脑“年轻化”（即发生神经可塑性的质变），提升认知健康及躯体健康水平。此外还探索了基因、脑结构和功能与认知老化之间的联系，为确定老年人认知功能下降的神经影像预警指标提供了多模态证据。这些研究成果为揭示脑老化和认知可塑性的本质，以及延缓认知衰退、预防神经退行性疾病提供了科学依据。.