健康与遗传心理学研究室知识库

主观认知下降(Subjective cognitive decline, SCD)是指部分老年人存在自我报 告记忆下降的问题，但其在客观认知测验上的成绩仍然处于正常范围之内。然而，SCD 老年人的认知能力下降速度更快，脑结构萎缩更严重，发展为认知障碍的风险也更高，因此，SCD 被公认为认知障碍发展的临床前阶段。相比于正常老年人，SCD 老年人的脑功能活动也出现变化，然而这种脑功能活动变化的具体意义还不明确，其中一个主要的原因是传统神经心理学测验或研究范式的敏感性较差，难以揭示正常老年人和 SCD 老年人的认知成绩差异，从而掩盖了脑功能活动和认知能力之间的真实关系。

基于此，本研究将采用对认知能力变化高度敏感的情景记忆范式—记忆相 似性任务，对正常老年人和 SCD 老年人的记忆辨别功能进行研究，以此来确定 SCD 老年人是否存在记忆辨别力下降，以及通过功能磁共振成像技术来确定 SCD 老年人与正常老年人记忆辨别力差异背后的认知神经机制是什么。

行为结果显示，SCD 老年人的各项神经心理学测验成绩与正常老年人相比 无显著差异，但 SCD 老年人的记忆辨别力显著低于正常老年人，且SCD 老年人的记忆辨别力下降具有普遍性，不会因材料辨别难度的增加而改变。功能磁共振成像结果显示，相比于正常老年人，SCD 老年人在正确记忆辨别时，左侧海马的激活水平显著下降，海马的激活水平与记忆辨别力存在显著正相关；在控制网络中，SCD 老年人在记忆辨别过程中左侧额下回和双侧内侧前额叶的激活水平显 著增加，且二者的激活水平与记忆辨别力存在显著负相关，但左侧额中回/额上回、双侧前扣带皮层、右侧楔前叶出现了激活水平显著降低的情况。任务态功能 连接结果显示，在记忆辨别中，SCD 老年人左侧海马种子点与双侧内侧前额叶、双侧楔前叶/后扣带皮层、左侧角回/颞中回的功能连接显著低于正常老年人，且种子点与这些脑区在正确记忆辨别条件下的功能连接与记忆辨别力存在显著正相关。

研究结果表明，SCD 老年人存在客观认知功能衰退，且这种记忆辨别功能衰退与额下回、内侧前额叶在克服相似刺激表征干扰时的神经效率降低有关，额中回/额上回的注意导向功能不足、前扣带皮层的冲突监测不足、以及楔前叶和海马在信息提取中的活动不足对记忆辨别力也有影响。此外，海马与其他核心回忆网络内脑区的功能连接降低所导致的脑区间信息交流障碍，对记忆辨别力下降也具有一定的作用。

本研究为 SCD 的临床概念提供了重要补充，并为 SCD 是认知障碍临床前阶段的观点提供了更多的证据支持，为认知障碍的早期识别提供了潜在的神经影像本研究为 SCD 的临床概念提供了重要补充，并为 SCD 是认知障碍临床前阶 段的观点提供了更多的证据支持，为认知障碍的早期识别提供了潜在的神经影像学标志物并为认知障碍的早期干预提供了可能的干预靶点。

Subjective cognitive decline (SCD) refers to the situation where elderly individuals report a decline in memory, but their performance on objective neuropsychological tests remains within the normal range. However, researches have shown that older adults with SCD tend to experience a faster decline in cognitive abilities, more severe brain structure atrophy, and a higher risk of developing cognitive impairment. Therefore, SCD is recognized as the preclinical stage of cognitive impairment. Changes in brain functional activity have also observed in elderly individuals with SCD compared to normal controls. However, the specific significance of these changes in brain functional activity is not yet clear. One challenge in studying SCD is the limited sensitivity of traditional neuropsychological tests or research paradigms, which makes it difficult to detect differences in cognitive performance between normal elderly individuals and those with SCD. This could mask the true relationship between changes in brain functional activity and cognitive abilities.

Hence, this study employed a highly sensitive episodic memory paradigm called the Mnemonic Similarity Task to investigate the mnemonic discrimination function of normal and SCD elderly individuals. The aim was to determine whether there was a decrease in mnemonic discrimination in SCD group and to understand the cognitive neural mechanisms underlying the difference in mnemonic discrimination between SCD and normal elderly individuals using functional magnetic resonance imaging (fMRI) technology.

The behavioral results of this study revealed no significant differences in the scores of various neuropsychological tests between SCD and normal elderly people. However, the mnemonic discrimination ability of SCD group was significantly lower than that of normal controls and this decline was consistent across different similarities.

The fMRI results revealed that elderly individuals with SCD exhibited reduced activation in the left hippocampus during accurate mnemonic discrimination compared to normal elderly individuals. Additionally, a significant positive correlation was observed between activation levels in the hippocampus and mnemonic discrimination scores. Within the control network, the SCD group demonstrated a significant increased activation in the left inferior frontal gyrus and bilateral medial prefrontal cortex during mnemonic discrimination. The activation levels of the inferior frontal gyrus and medial prefrontal cortex were found to be significantly negatively correlated with mnemonic discrimination scores. Conversely, there was a significant decrease in activation in the left middle frontal gyrus/superior frontal gyrus, bilateral anterior cingulate cortex, and right precuneus. The results of task-related functional connectivity indicated that during mnemonic discrimination, the functional connectivity between the seed region in the left hippocampus and the bilateral medial prefrontal cortex, bilateral precuneus/posterior cingulate cortex, and left angular gyrus/middle temporal gyrus in SCD group was significantly lower than that in normal controls. Moreover, the functional connectivity between the seed region and these brain regions during accurate discrimination was significantly positively correlated with mnemonic discrimination scores.

These findings indicated that elderly individuals with SCD experienced subtle cognitive decline. The decline in mnemonic discrimination was associated with reduced neural efficiency in overcoming interference between similar representations in the inferior frontal gyrus and medial prefrontal cortex. Insufficient attention guidance in the middle frontal gyrus/superior frontal gyrus, inadequate conflict monitoring in the anterior cingulate cortex, and dysfunction of the precuneus and hippocampus could also influence mnemonic discrimination. In addition, the decreased functional connectivity between the hippocampus and other brain regions within the core recollection network could lead to impaired communication between brain regions, which could also contribute to the decline of mnemonic discrimination.

The present study revised the clinical concept of SCD and provided additional evidence supporting the view that SCD is an indicator of the preclinical stage of cognitive impairment. Furthermore, it offered potential neuromarkers for early identification of cognitive impairment, and provided possible targets for early intervention in older adults.