Center for the Neurobiology of Learning and Memory, University of California, Irvine, California, USA.
Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
Hippocampus. 2022 Sep;32(9):627-638. doi: 10.1002/hipo.23456. Epub 2022 Jul 15.
Medial temporal lobe (MTL) atrophy is a core feature of age-related cognitive decline and Alzheimer's disease (AD). While regional volumes and thickness are often used as a proxy for neurodegeneration, they lack the sensitivity to serve as an accurate diagnostic test and indicate advanced neurodegeneration. Here, we used a submillimeter resolution diffusion weighted MRI sequence (ZOOMit) to quantify microstructural properties of hippocampal subfields in older adults (63-98 years old) using tensor derived measures: fractional anisotropy (FA) and mean diffusivity (MD). We demonstrate that the high-resolution sequence, and not a standard resolution sequence, identifies dissociable profiles for CA1, dentate gyrus (DG), and the collateral sulcus. Using ZOOMit, we show that advanced age is associated with increased MD of the CA1 and DG as well as decreased FA of the DG. Increased MD of the DG, reflecting decreased cellular density, mediated the relationship between age and word list recall. Further, increased MD in the DG, but not DG volume, was linked to worse spatial pattern separation. Our results demonstrate that ultrahigh-resolution diffusion imaging enables the detection of microstructural differences in hippocampal subfield integrity and will lead to novel insights into the mechanisms of age-related memory loss.
内侧颞叶（MTL）萎缩是与年龄相关的认知能力下降和阿尔茨海默病（AD）的核心特征。虽然区域体积和厚度通常被用作神经退行性变的替代物，但它们缺乏作为准确诊断测试的敏感性，并表明神经退行性变的进展。在这里，我们使用亚毫米分辨率弥散加权 MRI 序列（ZOOMit）使用张量衍生测量值来量化老年受试者（63-98 岁）海马亚区的微观结构特性：各向异性分数（FA）和平均扩散系数（MD）。我们证明，高分辨率序列而非标准分辨率序列可识别 CA1、齿状回（DG）和 collateral sulcus 的可分离图谱。使用 ZOOMit，我们表明，随着年龄的增长，CA1 和 DG 的 MD 增加以及 DG 的 FA 降低与年龄相关。DG 中 MD 的增加反映了细胞密度的降低，介导了年龄与单词列表回忆之间的关系。此外，DG 中 MD 的增加，而不是 DG 体积的增加，与较差的空间模式分离有关。我们的结果表明，超高分辨率弥散成像能够检测出海马亚区完整性的微观结构差异，并为与年龄相关的记忆丧失的机制提供新的见解。
