Department of Neuroradiology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Department of Neurophysiology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Neuroradiology. 2021 Sep;63(9):1481-1487. doi: 10.1007/s00234-021-02681-3. Epub 2021 Mar 4.
The lifetime risk of developing amyotrophic lateral sclerosis (ALS) increases in the elderly, and greater age at symptom onset has been identified as a negative prognostic factor in the disease. However, the underlying neurobiological mechanisms are still poorly investigated. We hypothesized that older age at symptom onset would have been associated with greater extra-motor cortical damage contributing to worse prognosis, so we explored the relationship between age at symptom onset, cortical thinning (CT) distribution, and clinical markers of disease progression.
We included 26 ALS patients and 29 healthy controls with T1-weighted magnetic resonance imaging (MRI). FreeSurfer 6.0 was used to identify regions of cortical atrophy (CA) in ALS, and to relate age at symptom onset to CT distribution. Linear regression analyses were then used to investigate whether MRI metrics of age-related damage were predictive of clinical progression. MRI results were corrected using the Monte Carlo simulation method, and regression analyses were further corrected for disease duration.
ALS patients exhibited significant CA mainly encompassing motor regions, but also involving the cuneus bilaterally and the right superior parietal cortex (p < 0.05). Older age at symptom onset was selectively associated with greater extra-motor (frontotemporal) CT, including pars opercularis bilaterally, left middle temporal, and parahippocampal cortices (p < 0.05), and CT of these regions was predictive of shorter survival (p = 0.004, p = 0.03).
More severe frontotemporal CT contributes to shorter survival in older ALS patients. These findings have the potential to unravel the neurobiological mechanisms linking older age at symptom onset to worse prognosis in ALS.
肌萎缩侧索硬化症（ALS）的终生发病风险随年龄增长而增加，症状出现时的年龄较大已被确定为该疾病的一个负性预后因素。然而，其潜在的神经生物学机制仍未得到充分研究。我们假设症状出现时的年龄较大与更大的运动皮层外损伤有关，从而导致更差的预后，因此我们探讨了症状出现时的年龄、皮质变薄（CT）分布与疾病进展的临床标志物之间的关系。
我们纳入了 26 名 ALS 患者和 29 名健康对照者，他们均接受了 T1 加权磁共振成像（MRI）检查。使用 FreeSurfer 6.0 识别 ALS 中的皮质萎缩（CA）区域，并将症状出现时的年龄与 CT 分布相关联。然后，我们使用线性回归分析来研究 MRI 测量的与年龄相关的损伤指标是否可预测临床进展。使用蒙特卡罗模拟方法对 MRI 结果进行校正，并进一步针对疾病持续时间对回归分析进行校正。
ALS 患者表现出明显的 CA，主要累及运动区域，但也累及双侧楔前叶和右侧顶上回（p < 0.05）。症状出现时的年龄较大与更大的运动皮层外 CT 相关，包括双侧额下回、左颞中回和海马旁回（p < 0.05），这些区域的 CT 与较短的生存时间相关（p = 0.004，p = 0.03）。
更严重的额颞 CT 增加了老年 ALS 患者的生存时间。这些发现有可能揭示将症状出现时的年龄较大与 ALS 中更差的预后联系起来的神经生物学机制。
