Zhu Alyssa H, Nir Talia M, Javid Shayan, Villalón-Reina Julio E, Rodrigue Amanda L, Strike Lachlan T, de Zubicaray Greig I, McMahon Katie L, Wright Margaret J, Medland Sarah E, Blangero John, Glahn David C, Kochunov Peter, Williamson Douglas E, Håberg Asta K, Thompson Paul M, Jahanshad Neda
Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
Department of Biomedical Engineering, USC Viterbi School of Engineering, Los Angeles, CA, USA.
Sci Data. 2025 May 6;12(1):748. doi: 10.1038/s41597-025-05028-2.
Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data and used to assess the effect of the ApoE4 risk factor for dementia in WM across the lifespan. We found significant associations between ApoE4 and FA in WM regions associated with neurodegenerative disease even in healthy individuals across the lifespan, with regional age-by-genotype interactions. Our lifespan reference curves and tools to harmonize new dMRI data to the curves are publicly available as eHarmonize ( https://github.com/ahzhu/eharmonize ).
与年龄相关的白质（WM）微观结构的成熟和衰退贯穿人类一生，与灰质的发育和退化过程相辅相成。在此，我们通过整合来自十个公共数据集（N = 40898名受试者；年龄：3至95岁；男性占47.6%）的扩散磁共振成像（dMRI）数据，创建了全球和区域WM微观结构的标准寿命参考曲线。我们在基于区域扩散张量成像（DTI）的分数各向异性（FA）上测试了三种整合方法，FA是使用ENIGMA-DTI管道提取的WM微观结构指标。ComBat-GAM整合提供了与已知WM成熟峰值最一致的多研究轨迹。寿命FA参考曲线通过重测数据进行了验证，并用于评估载脂蛋白E4（ApoE4）痴呆风险因素在整个生命周期中对WM的影响。我们发现，即使在整个生命周期的健康个体中，ApoE4与与神经退行性疾病相关的WM区域中的FA之间也存在显著关联，存在区域年龄与基因型的相互作用。我们的寿命参考曲线以及将新的dMRI数据与曲线进行整合的工具可通过eHarmonize（https://github.com/ahzhu/eharmonize）公开获取。
