Khodadadi Arpanahi Sobhan, Hamidpour Shahrbanoo, Ghasvarian Jahromi Khatereh
Department of Biomedical and Electrical Engineering, ACECR, Isfahan, Iran.
Ageing Res Rev. 2025 Apr;106:102688. doi: 10.1016/j.arr.2025.102688. Epub 2025 Feb 11.
Despite normal cognitive abilities, subjective memory complaints (SMC) are common in older adults and are linked to mild memory impairment. SMC may be a sign of subtle cognitive decline and underlying pathological changes, according to research; however, there is not enough data to support the use of resting-state functional connectivity to identify early changes in the brain network before cognitive symptoms manifest.
In this study, the topological structure and regional connectivity of the brain functional network in SMC individuals were analyzed using graph theoretical analysis in both weighted and binarized network models, alongside healthy controls. Resting-state functional magnetic resonance imaging data was collected from 24 SMCs and 39 cognitively normal people. Analysis of both binary and weighted graph theory was done using the Dosenbach Atlas as a basis based on area under curves (AUCs) for the graph network parameters, which comprised of six node metrics and nine global measures. We then performed group comparisons using statistical analyses based on Network-Based Statistics functional connectomes. Finally, the relationship between global graph measures and cognition was examined using neuropsychological tests such as the Mini-Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale (ADAS score).
The topologic properties of brain functional connectomes at both global and nodal levels were tested. The SMC patients showed increased functional connectivity in clustering coefficient global (P < 0.00001), global efficiency (P < 0.00001), and normalized characteristic path length or Lambda (P < 0.00001), while there was decreased functional connectivity in Modularity (P < 0.04542), characteristic path length (0.00001), and small-worldness or Sigma (P < 0.00001) in binary networks model. In contrast, SMC patients only exhibited decreased functional connectivity in Assortativity identified by weighted networks model. Furthermore, some brain regions located in the default mode network, sensorimotor, occipital, and cingulo-opercular network in SMC patients showed altered nodal centralities. No significant correlation was found between global metrics and MMSE scores in both groups using binary metrics. However, in cognitively normal individuals, negative correlation was observed with weighted metrics in global and local efficiency and Lambda. While In SMC patients, a significant positive correlation was found between ADAS scores and local efficiency in both binary and weighted metrics.
The findings suggest that functional impairments in SMC patients might be associated with disruptions in the global and regional topological organization of the brain's functional connectome, offering new and significant insights into the pathophysiological mechanisms underlying SMC.
尽管认知能力正常，但主观记忆抱怨（SMC）在老年人中很常见，并且与轻度记忆障碍有关。根据研究，SMC可能是细微认知衰退和潜在病理变化的一个迹象；然而，没有足够的数据支持在认知症状出现之前使用静息态功能连接来识别大脑网络的早期变化。
在本研究中，使用加权和二值化网络模型的图论分析，对SMC个体与健康对照者的大脑功能网络的拓扑结构和区域连接性进行了分析。从24名SMC患者和39名认知正常的人那里收集了静息态功能磁共振成像数据。基于图网络参数的曲线下面积（AUC），以多森巴赫图谱为基础，对二值化和加权图论进行了分析，图网络参数包括六个节点指标和九个全局测量值。然后，我们使用基于网络统计功能连接组的统计分析进行组间比较。最后，使用简易精神状态检查表（MMSE）和阿尔茨海默病评估量表（ADAS评分）等神经心理学测试，研究了全局图测量值与认知之间的关系。
测试了大脑功能连接组在全局和节点水平的拓扑特性。SMC患者在全局聚类系数（P < 0.00001）、全局效率（P < 0.00001）和归一化特征路径长度或λ（P < 0.00001）方面显示功能连接性增加，而在二值网络模型中，模块性（P < 0.04542）、特征路径长度（0.00001）和小世界特性或σ（P < 0.00001）方面功能连接性降低。相比之下，SMC患者仅在加权网络模型确定的 assortativity 方面表现出功能连接性降低。此外，SMC患者中位于默认模式网络、感觉运动、枕叶和扣带回 - 岛盖网络的一些脑区显示节点中心性改变。在两组中，使用二值化指标时，未发现全局测量值与MMSE评分之间存在显著相关性。然而，在认知正常的个体中，观察到全局和局部效率以及λ的加权指标呈负相关。而在SMC患者中，ADAS评分与二值化和加权指标下的局部效率之间存在显著正相关。
研究结果表明，SMC患者的功能损害可能与大脑功能连接组的全局和区域拓扑组织破坏有关，为SMC潜在的病理生理机制提供了新的重要见解。
