Data_Sheet_1_Hippocampal microstructure, but not macrostructure, mediates age differences in episodic memory.docx

IntroductionSeparate unimodal magnetic resonance imaging (MRI) literatures have shown that hippocampal gray matter macrostructure (volume) and microstructure (diffusion) decline with age and relate to episodic memory performance, with multimodal MRI studies reporting that episodic memory may be better explained by a combination of these metrics. However, these effects are often assessed independent of age or only within older adults and therefore do not address whether these distinct modalities explain variance in (i.e, mediate) the effect of age on episodic memory.MethodsHere, we simultaneously examined the unique and joint contribution of hippocampal volume and diffusion to age-related differences in episodic memory in 83 younger and 61 older adults who underwent a T1- and diffusion-weighted MRI and completed the Rey Auditory Verbal Learning Test.ResultsAs expected, older age was significantly related to smaller volume and higher diffusion (intracellular, dispersion, and free) in bilateral hippocampus and to worse episodic memory performance (immediate and delayed free recall, recognition). Structural equation modelling revealed that the age-memory relationship was significantly mediated by hippocampal diffusion, but not volume. A non-significant influential indirect effect further revealed that the structural metrics did not jointly mediate the age-memory relationship.DiscussionTogether, these findings indicate that hippocampal microstructure uniquely contributes to age-related differences in episodic memory and suggest that volume and diffusion capture distinct neurobiological properties of hippocampal gray matter.

引言：独立于单模态磁共振成像（MRI）文献已表明，海马灰质宏观结构（体积）与微观结构（扩散）随年龄增长而衰退，并与情景记忆表现相关。多模态MRI研究则报告称，情景记忆可能通过这些指标的组合得到更好的解释。然而，这些效应通常在独立于年龄或仅在老年人群体内进行评估，因此未能解释这些不同的模态是否解释了年龄对情景记忆影响的差异。方法：在本研究中，我们同时考察了83名青年和61名老年人在接受T1加权与扩散加权MRI扫描并完成雷伊听觉语言学习测试后，海马体积与扩散对与年龄相关的情景记忆差异的独特和联合贡献。结果：如预期，随着年龄的增长，双侧海马体积减小，扩散（细胞内、弥散和自由）增加，并且情景记忆表现（即刻和延迟自由回忆、识别）变差。结构方程模型显示，年龄与记忆之间的关系被海马扩散显著中介，但不是体积。一个非显著的有影响力的间接效应进一步揭示，结构指标并未共同中介年龄与记忆之间的关系。讨论：综合这些发现，表明海马微观结构独特地贡献于与年龄相关的情景记忆差异，并暗示体积与扩散捕捉到了海马灰质的独特神经生物学特性。