Pang Huize, Sun Zhe, Liang Zifei, Li Chenyang, Zhang Jiangyang, Ge Yulin
Department of Radiology, NYU Grossman School of Medicine, New York, New York, USA.
Hum Brain Mapp. 2025 Oct 1;46(14):e70321. doi: 10.1002/hbm.70321.
While hippocampal atrophy in Alzheimer's disease is well-documented, research on microstructural integrity of hippocampal pathways to selected cortical regions in healthy aging populations remains limited. Four hundred seventy-five healthy individuals aged 36-90 from the Human Connectome Project Aging (HCP-A) dataset were analyzed. Hippocampal fiber pathways, including the "Papez," "Prefrontal," "Occipital," and "Parietal" pathways, were extracted from whole-brain tractography and characterized by fractional anisotropy (FA) and mean diffusivity (MD), neurite density index (NDI), and orientation distribution index (ODI). Partial linear and quadratic nonlinear correlation analyses were conducted to examine the relationship between age, cognition, and diffusion metrics, adjusted by hippocampus volumes. While FA, MD, and ODI demonstrated linear age-related changes, NDI exhibited a quadratic pattern. MD was identified as the most age-sensitive parameter. Among all pathways, the "Prefrontal" pathway showed the most pronounced microstructural changes in both males and females, characterized by reduced FA and NDI and increased MD and ODI with age (FA: r = -0.31 to -0.40; NDI: r = 0.30-0.31; MD/ODI: r = 0.23-0.48; p < 0.01). Similar changes were observed in the "Occipital" pathway (FA: r = -0.28 to -0.39; MD/ODI: r = 0.32-0.50; p < 0.01), with NDI reduction present only in females (r = 0.18, p < 0.01). In the "Parietal" pathway, changes were detected only in females, with lower FA (r = -0.29, p < 0.01) and higher ODI (r = 0.24, p < 0.01). Additionally, age-related cognitive decline was significantly associated with microstructural changes in the "Occipital" (FA: r = 0.29; MD: r = -0.28; ODI: r = -0.25; p < 0.001) and "Prefrontal" pathways (FA: r = 0.27; MD: r = -0.25; NDI: r = 0.25; ODI: r = -0.22; p < 0.01) in females. This study revealed age- and cognition-related changes in hippocampal pathways across the adult lifespan. These findings provide normative references for hippocampal-cortical connectivity changes associated with healthy aging and its potential relevance to Alzheimer's disease and related dementias.
虽然阿尔茨海默病中海马萎缩已有充分记录，但针对健康老年人群中连接海马与特定皮质区域的神经通路微观结构完整性的研究仍然有限。对来自人类连接组计划衰老（HCP-A）数据集的475名年龄在36至90岁的健康个体进行了分析。从全脑纤维束成像中提取包括“帕佩兹”“前额叶”“枕叶”和“顶叶”通路在内的海马纤维通路，并通过分数各向异性（FA）、平均扩散率（MD）、神经突密度指数（NDI）和方向分布指数（ODI）进行表征。进行了部分线性和二次非线性相关分析，以研究年龄、认知与扩散指标之间的关系，并对海马体积进行了校正。虽然FA、MD和ODI呈现出与年龄相关的线性变化，但NDI呈现出二次模式。MD被确定为对年龄最敏感的参数。在所有通路中，“前额叶”通路在男性和女性中均表现出最明显的微观结构变化，其特征是随着年龄增长FA和NDI降低，MD和ODI增加（FA：r = -0.31至-0.40；NDI：r = 0.30 - 0.31；MD/ODI：r = 0.23 - 0.48；p < 0.01）。在“枕叶”通路中也观察到类似变化（FA：r = -0.28至-0.39；MD/ODI：r = 0.32 - 0.50；p < 0.01），NDI降低仅在女性中出现（r = 0.18，p < 0.01）。在“顶叶”通路中，仅在女性中检测到变化，FA较低（r = -0.29，p < 0.01），ODI较高（r = 0.24，p < 0.01）。此外，与年龄相关的认知衰退与女性“枕叶”（FA：r = 0.29；MD：r = -0.28；ODI：r = -0.25；p < 0.001）和“前额叶”通路（FA：r = 0.27；MD：r = -0.25；NDI：r = 0.25；ODI：r = -0.22；p < 0.01）的微观结构变化显著相关。这项研究揭示了成年期海马通路中与年龄和认知相关的变化。这些发现为与健康衰老相关的海马 - 皮质连接变化及其与阿尔茨海默病和相关痴呆症的潜在关联提供了规范性参考。
