Shin Young Seon, Christensen Danielle, Wang Jingying, Shirley Desirae J, Orlando Ann-Marie, Romero Regilda A, Vaillancourt David E, Wilkes Bradley J, Coombes Stephen A, Wang Zheng
Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, PO Box 118206, Gainesville, FL, 32611-8205, USA.
Neurocognitive and Behavioral Development Laboratory, Department of Applied Physiology and Kinesiology, University of Florida, PO Box 118206, Gainesville, FL, 32611-8205, USA.
Mol Autism. 2025 Mar 6;16(1):16. doi: 10.1186/s13229-025-00652-6.
Autism spectrum disorder (ASD) is a lifelong condition that profoundly impacts health, independence, and quality of life. However, research on brain aging in autistic adults is limited, and microstructural variations in white and gray matter remain poorly understood. To address this critical gap, we assessed novel diffusion MRI (dMRI) biomarkers, free water, and free water corrected fractional anisotropy (fwcFA), and mean diffusivity (fwcMD) across 32 transcallosal tracts and their corresponding homotopic grey matter origin/endpoint regions of interest (ROIs) in middle and old aged autistic adults.
Forty-three autistic adults aged 30-73 and 43 age-, sex-, and IQ-matched neurotypical controls underwent dMRI scans. We examined free water, fwcFA, fwcMD differences between the two groups and age-related pattern of each dMRI metric across the whole brain for each group. The relationships between clinical measures of ASD and free water in regions that significantly differentiated autistic adults from neurotypical controls were also explored. In supplementary analyses, we also assessed free water uncorrected FA and MD using conventional single tensor modeling.
Autistic adults exhibited significantly elevated free water in seven frontal transcallosal tracts compared to controls. In controls, age-related increases in free water and decreases in fwcFA were observed across most transcallosal tracts. However, these age-associated patterns were entirely absent in autistic adults. In gray matter, autistic adults showed elevated free water in the calcarine cortices and lower fwcMD in the dorsal premotor cortices compared to controls. Lastly, age-related increases in free water were found across all white matter and gray matter ROIs in neurotypical controls, whereas no age-related associations were detected in any dMRI metrics for autistic adults.
We only recruited cognitively capable autistic adults, which limits the generalizability of our findings across the full autism spectrum. The cross-sectional design precludes inferences about microstructural changes over time in middle and old aged autistic adults.
Our findings revealed increased free water load in frontal white matter in autistic adults and identified distinct age-associated microstructural variations between the two groups. These findings highlight more heterogeneous brain aging profiles in autistic adults. Our study also demonstrated the importance of quantifying free water in dMRI studies of ASD.
自闭症谱系障碍（ASD）是一种终身疾病，对健康、独立性和生活质量有深远影响。然而，关于自闭症成年人脑老化的研究有限，白质和灰质的微观结构变化仍知之甚少。为了填补这一关键空白，我们评估了新的扩散磁共振成像（dMRI）生物标志物、自由水、自由水校正分数各向异性（fwcFA）以及平均扩散率（fwcMD），这些指标涉及32条胼胝体束及其在中老年自闭症成年人中相应的同侧灰质起源/终点感兴趣区域（ROI）。
43名年龄在30 - 73岁的自闭症成年人以及43名年龄、性别和智商匹配的神经典型对照者接受了dMRI扫描。我们检查了两组之间的自由水、fwcFA、fwcMD差异，以及每组全脑各dMRI指标与年龄相关的模式。还探讨了ASD临床指标与在将自闭症成年人与神经典型对照者显著区分开的区域中的自由水之间的关系。在补充分析中，我们还使用传统单张量模型评估了未校正自由水的FA和MD。
与对照组相比，自闭症成年人在七条额叶胼胝体束中自由水显著升高。在对照组中，在大多数胼胝体束中观察到自由水随年龄增加以及fwcFA随年龄降低。然而，这些与年龄相关的模式在自闭症成年人中完全不存在。在灰质中，与对照组相比，自闭症成年人在距状皮质中自由水升高，在背侧运动前皮质中fwcMD降低。最后，在神经典型对照者的所有白质和灰质ROI中发现自由水随年龄增加，而在自闭症成年人的任何dMRI指标中均未检测到与年龄相关的关联。
我们仅招募了有认知能力的自闭症成年人，这限制了我们的研究结果在整个自闭症谱系中的普遍性。横断面设计排除了对中老年自闭症成年人随时间的微观结构变化的推断。
我们的研究结果揭示了自闭症成年人额叶白质中自由水负荷增加，并确定了两组之间不同的与年龄相关的微观结构变化。这些发现突出了自闭症成年人中更具异质性的脑老化特征。我们的研究还证明了在ASD的dMRI研究中量化自由水的重要性。
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