Schulz Maximilian, Mayer Carola, Schlemm Eckhard, Frey Benedikt M, Malherbe Caroline, Petersen Marvin, Gallinat Jürgen, Kühn Simone, Fiehler Jens, Hanning Uta, Twerenbold Raphael, Gerloff Christian, Cheng Bastian, Thomalla Götz
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Computational Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Front Aging Neurosci. 2022 Feb 25;14:782738. doi: 10.3389/fnagi.2022.782738. eCollection 2022.
Aging is accompanied by structural brain changes that are thought to underlie cognitive decline and dementia. Yet little is known regarding the association between increasing age, structural brain damage, and alterations of functional brain connectivity. The aim of this study was to evaluate whether cortical thickness and white matter damage as markers of age-related structural brain changes are associated with alterations in functional connectivity in non-demented healthy middle-aged to older adults. Therefore, we reconstructed functional connectomes from resting-state functional magnetic resonance imaging (MRI) (rsfMRI) data of 976 subjects from the Hamburg City Health Study, a prospective population-based study including participants aged 45-74 years from the metropolitan region Hamburg, Germany. We performed multiple linear regressions to examine the association of age, cortical thickness, and white matter damage quantified by the peak width of skeletonized mean diffusivity (PSMD) from diffusion tensor imaging on whole-brain network connectivity and four predefined resting state networks (default mode, dorsal, salience, and control network). In a second step, we extracted subnetworks with age-related decreased functional connectivity from these networks and conducted a mediation analysis to test whether the effect of age on these networks is mediated by decreased cortical thickness or PSMD. We observed an independent association of higher age with decreased functional connectivity, while there was no significant association of functional connectivity with cortical thickness or PSMD. Mediation analysis identified cortical thickness as a partial mediator between age and default subnetwork connectivity and functional connectivity within the default subnetwork as a partial mediator between age and executive cognitive function. These results indicate that, on a global scale, functional connectivity is not determined by structural damage in healthy middle-aged to older adults. There is a weak association of higher age with decreased functional connectivity which, for specific subnetworks, appears to be mediated by cortical thickness.
衰老伴随着大脑结构的变化，这些变化被认为是认知能力下降和痴呆的基础。然而，关于年龄增长、大脑结构损伤和大脑功能连接改变之间的关联，我们知之甚少。本研究的目的是评估作为与年龄相关的大脑结构变化标志物的皮质厚度和白质损伤是否与非痴呆健康中老年人的功能连接改变有关。因此，我们从汉堡城市健康研究的976名受试者的静息态功能磁共振成像（rsfMRI）数据中重建了功能连接组，该研究是一项基于人群的前瞻性研究，参与者年龄在45 - 74岁之间，来自德国汉堡大都市地区。我们进行了多元线性回归，以检验年龄、皮质厚度和通过扩散张量成像的骨架化平均扩散率峰值宽度（PSMD）量化的白质损伤与全脑网络连接性以及四个预定义静息状态网络（默认模式、背侧、突显和控制网络）之间的关联。在第二步中，我们从这些网络中提取了功能连接性随年龄下降的子网，并进行了中介分析，以测试年龄对这些网络的影响是否由皮质厚度或PSMD的下降介导。我们观察到年龄越大与功能连接性下降之间存在独立关联，而功能连接性与皮质厚度或PSMD之间无显著关联。中介分析确定皮质厚度是年龄与默认子网连接性之间的部分中介，默认子网内的功能连接性是年龄与执行认知功能之间的部分中介。这些结果表明，在全球范围内，健康中老年人的功能连接性不由结构损伤决定。年龄越大与功能连接性下降之间存在微弱关联，对于特定子网，这种关联似乎由皮质厚度介导。
