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. 2025 Jul 2;25(1):452.
doi: 10.1186/s12877-025-06072-8.

Cognitive reserve in subjective cognitive decline with worry: DMN-VN connectivity supports episodic memory under structural vulnerability

Lanli Jiang  1   2 , Shaokun Zhao  1   2 , Ting Li  1   2 , Jiawen Liu  1   2 , Junyin Zhang  3 , Zhanjun Zhang  4   5 , Xin Li  6   7
Affiliations

Cognitive reserve in subjective cognitive decline with worry: DMN-VN connectivity supports episodic memory under structural vulnerability

Lanli Jiang et al. BMC Geriatr. .

Abstract

Background: The occurrence of worry in subjects with Subjective Cognitive Decline(SCD) confers a greater risk of future AD and cognitive decline. However, it is not known whether these individuals have distinct memory and neuroimaging profiles. Therefore, we aimed to identify brain imaging characteristics associated with episodic memory in elderly adults with subjective cognitive decline and related worry (SCD+) in a population-based cohort.

Methods: A total of 418 individuals from the BABRI cohort underwent structural MRI (n = 418) and episodic memory-related task-based fMRI (n = 153) scans. The subjects were classified into Mild Cognitive Impairment (MCI), SCD+ , SCD, and Normal Control (NC) groups. A brain structure-function-episodic memory pathway model was constructed to investigate potential compensatory mechanisms.

Results: Cognitively, SCD+ group did not perform significantly worse than SCD group on episodic memory tasks. For the structural T1-weighted MRI results, gray matter integrity in SCD+ group exhibited altered atrophy patterns compared to SCD, mainly in the posterior hippocampus and parahippocampal cortex. Using PsychoPhysiological Interactions (PPI) to investigate task-based functional connectivity, we found that the SCD+ group exhibited significantly stronger functional connectivity (FC) in the Default Mode Network (DMN) and other networks than SCD. Using moderation model analysis, we found that stronger FC between the DMN and Visual Network (VN) moderated the relationship between gray matter volume (GM) of the posterior hippocampus and episodic memory encoding accuracy within SCD+ group.

Conclusions: Stronger DMN-VN connectivity may reflect early cognitive reserve processes supporting episodic memory in SCD+ despite structural vulnerability, although such adaptations may vunerable as Alzheimer's disease progresses. Task-based fMRI may serve as a sensitive tool for detecting these processes before clinical decline.

Keywords: Cognitive reserve; Default mode network; Episodic memory; Subjective cognitive decline with related worry; Visual network.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: We confirm that the research described in our manuscript adheres to the principles outlined in the Declaration of Helsinki. Written informed consent was obtained from each participant, and the use of human subjects was approved by the Institutional Review Board (IRB) at the Imaging Center for Brain Research at Beijing Normal University(ICBIR_A_0041_002_02). All methods were performed following the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Differences in GM between groups in the posterior hippocampus and its partial correlation with episodic memory performance. A. Diagram of the anatomical locations of the anterior and posterior hippocampus; B. Intergroup differences in posterior hippocampus GM; C, D. Partial correlations of posterior hippocampus GM with episodic memory scores, controlling for TIV, sex, age, and level of education
Fig. 2
Fig. 2
A. Intergroup differences in brain functional network connectivity strength during the encoding and retrieval stages; B, C: Brain map showing the stronger functional connectivity in SCD + group than in SCD group
Fig. 3
Fig. 3
The effect of posterior hippocampal GM on the accuracy of episodic memory encoding is modulated by the functional connectivity strength between the DMN and VN networks during the encoding phase. A. Conceptual diagram of the moderation model in which the effect of the focal antecedent (X) on the outcome (Y) is influenced or dependent on a moderator (W); B. Moderate effect: the two-way interaction effect plot shows that when the functional connectivity strength between the DMN-VN is high, even a smaller volume of the poHIP can maintain high encoding accuracy; C. Schematic representation of the brain regions with enhanced DMN-VN functional connectivity and the poHIP
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