A research team led by Professor LI Juan from the Institute of Psychology, Chinese Academy of Sciences has uncovered how subtle brain network disruptions in older adults with subjective cognitive decline (SCD)—a potential early warning sign of Alzheimer’s disease—lead to previously undetected memory impairments. Published in Alzheimer’s & Dementia, this research bridges the gap between clinical observations and neural mechanisms, offering a new framework to understand the pathology of brain diseases.

SCD refers to self-reported memory complaints despite normal neuropsychological test scores, and it is often considered the earliest preclinical stage of Alzheimer’s. While prior studies identified abnormalities in brain regions like the medial temporal lobe, the lack of sensitive cognitive neuroscience tools left critical questions unanswered: Do these abnormalities cause measurable memory deficits? How do brain networks collaborate—or fail—during complex memory tasks?

To address these questions, the team recruited community-dwelling older adults with SCD and cognitively normal peers. Using a novel mnemonic similarity task (MST)—a high-precision memory paradigm requiring detailed encoding and retrieval—combined with task-based fMRI, the researchers mapped brain activity during memory processes. The MST specifically targets the medial temporal lobe (including the hippocampus) and the control network (prefrontal and posterior parietal cortex), areas implicated in SCD pathology.

Behavioral results revealed no significant differences in general cognitive scores between the two groups. However, SCD participants showed a striking tendency to misclassify similar images as identical old ones and displayed significantly weaker high-fidelity memory performance. “This suggests SCD individuals have objective memory impairments that conventional tests overlook,” explained Prof. LI.

Neuroimaging uncovered deeper mechanisms. During high-fidelity memory retrieval, the SCD group exhibited reduced activation in the left hippocampus—a hub for detailed memory—and hyperactivity in prefrontal control regions. Functional connectivity analyses further showed weakened interactions between the hippocampus and key integration areas like the precuneus and angular gyrus. Notably, the angular gyrus, a critical hub for information transfer, displayed disrupted connections with both the hippocampus and control network. Mediation analysis further confirmed that abnormal hippocampal-control network coordination, compounded by impaired integration in the angular gyrus, directly contributes to memory deficits.

This study highlights the power of combining clinical insights with advanced neuroscience tools to uncover early signs of cognitive decline. “By pinpointing how brain networks fail during specific tasks, we move closer to early intervention strategies,” said Prof. LI. The findings also underscore the need for interdisciplinary collaboration to bridge the gaps between molecular pathology and cognitive symptoms in Alzheimer’s research.

This study entitled "Disrupted Brain Networks Underlying High-Fidelity Memory Retrieval in Subjective Cognitive Decline: A Task-Based fMRI Study"  was funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China, among other sources.

Fig.1 Behavioral results of MST in different groups. Panel (A): Proportion of responses for each item type. Responses to lure items differed between SCD and NC, while SCD responded fewer “similar” and more “old” to lure items than NC. Panel (B): SCD showed lower LDI compared with NC, warm color represents NC and cool color represents SCD. Error bars represent the standard error of the means. ***p < 0.001. LDI, lure discrimination index; MST, mnemonic similarity task; NC, normal controls; SCD, subjective cognitive decline. Image by Dr. LI Juan.