Mohammadi Sana, Ghaderi Sadegh, Fatehi Farzad, Kalra Sanjay, Batouli Seyed Amir Hossein
Neuromuscular Research Center, Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Brain Behav. 2025 May;15(5):e70484. doi: 10.1002/brb3.70484.
This longitudinal study investigated pathological brain aging in amyotrophic lateral sclerosis (ALS) by evaluating disparities between chronological age and deep learning-derived brain structure age (BSA) and exploring associations with cognitive and functional decline.
Ten limb-onset ALS patients (seven males) and 10 demographically matched healthy controls (HCs) underwent structural magnetic resonance imaging (sMRI) and cognitive assessments at baseline and follow-up. The BSA was estimated using the validated volBrain platform. Cognitive domains (language, verbal fluency, executive function, memory, and visuospatial skills) and global cognition (Persian adaptive Edinburgh Cognitive and Behavioral ALS Screen [ECAS] total score) were assessed along with functional status (ALSFRS-R).
ALS patients exhibited significant BSA-chronological age disparities at baseline (Δ = +7.31 years, p = 0.009) and follow-up (Δ = +8.39 years, p = 0.003), with accelerated BSA progression over time (p = 0.004). The HCs showed no such disparities (p = 0.931). Longitudinal BSA increases were correlated with executive function decline (r = -0.651, p = 0.042). Higher education predicted preserved language (r = 0.831, p = 0.003) and verbal fluency (r = 0.738, p = 0.015). ALSFRS-R decline paralleled visuospatial (r = 0.642, p = 0.045) and global cognitive deterioration (r = 0.667, p = 0.035).
ALS is characterized by accelerated structural brain aging that progresses independently of chronological age and is correlated with executive dysfunction. Education may mitigate cognitive decline, while motor functional deterioration aligns with visuospatial and global cognitive impairments. BSA has emerged as a potential biomarker for tracking pathological aging trajectories in ALS, warranting validation using larger cohorts.
这项纵向研究通过评估实际年龄与深度学习衍生的脑结构年龄（BSA）之间的差异，并探索其与认知和功能衰退的关联，来研究肌萎缩侧索硬化症（ALS）患者的病理性脑老化情况。
10例肢体起病的ALS患者（7例男性）和10例人口统计学匹配的健康对照者（HCs）在基线和随访时接受了结构磁共振成像（sMRI）和认知评估。使用经过验证的volBrain平台估算BSA。评估了认知领域（语言、言语流畅性、执行功能、记忆和视觉空间技能）和整体认知（波斯语适应性爱丁堡认知和行为ALS筛查[ECAS]总分）以及功能状态（ALSFRS-R）。
ALS患者在基线时（Δ = +7.31岁，p = 0.009）和随访时（Δ = +8.39岁，p = 0.003）表现出显著的BSA-实际年龄差异，且随着时间推移BSA进展加速（p = 0.004）。HCs未表现出此类差异（p = 0.931）。纵向BSA增加与执行功能衰退相关（r = -0.651，p = 0.042）。高等教育预示着语言能力（r = 0.831，p = 0.003）和言语流畅性得以保留（r = 0.738，p = 0.015）。ALSFRS-R下降与视觉空间功能（r = 0.642，p = 0.045）和整体认知恶化（r = 0.667，p = 0.035）平行。
ALS的特征是脑结构加速老化，其进展独立于实际年龄，且与执行功能障碍相关。教育可能减轻认知衰退，而运动功能恶化与视觉空间和整体认知障碍一致。BSA已成为追踪ALS病理性老化轨迹的潜在生物标志物，需要使用更大的队列进行验证。
