Memory impairment in motor neuron disease (MND) is still an underrecognized feature and has traditionally been attributed to executive dysfunction. Here, we investigate the rate of memory impairment in a longitudinal cohort of MND patients, its relationship to other cognitive functions and the underlying neuroanatomical correlates. 142 patients with MND and 99 healthy controls (HC) underwent comprehensive neuropsychological testing and structural MRI at 3T up to four times over a period of 18 months. Linear-mixed effects models were fitted to identify changes at baseline and over time in episodic memory function (learning, immediate and delayed recall, recognition), composed cognitive scores (memory, verbal fluency, executive function), and memory-related structural brain regions (hippocampus, entorhinal cortex, parahippocampal gyrus). Associations between episodic memory performance and volumetric or cortical thickness changes of these regions were computed using Pearson's r. Learning, immediate and delayed recall, as well as recognition performance were significantly reduced in MND when compared to controls at baseline. Performances in these subtests improved over time although MND showed less improvement than controls. This relationship did not change when only “classical” ALS patients were considered. Patients with MND showed thinning of the right parahippocampal gyrus (PhG) in comparison to controls that was progressing over time. Bilateral hippocampal atrophy was observed in MND patients with memory impairment after splitting the group according to their overall episodic memory performance, with the right hippocampus shrinking over time. In MND patients, the bilateral hippocampal atrophy was associated with impairment in learning, recall, and recognition at baseline. In contrast, left PhG thinning was associated with a poorer learning performance. These results show that episodic memory impairment in MND is a frequent cognitive dysfunction. Since deficits are not clearly declining with disease course, an early involvement of this cognitive domain in the disease seems probable. The memory performance-dependent atrophy of the hippocampus and PhG provide evidence for a widespread involvement of these non-motor cortical areas in disease pathology.

运动神经元疾病（MND）中的记忆障碍仍然是一个未被充分认识的特征，传统上被归因于执行功能障碍。在这里，我们研究了 MND 患者纵向队列中的记忆障碍发生率、其与其他认知功能的关系以及潜在的神经解剖学相关性。142 名 MND 患者和 99 名健康对照 (HC) 在 18 个月的时间内接受了四次全面的神经心理学测试和 3T 结构 MRI。拟合线性混合效应模型来识别情景记忆功能（学习、即时和延迟回忆、识别）、组成认知评分（记忆、语言流畅性、执行功能）以及与记忆相关的大脑结构区域在基线和随时间的变化（海马体、内嗅皮层、海马旁回）。使用 Pearson's r计算情景记忆表现与这些区域的体积或皮质厚度变化之间的关联。与基线对照相比，MND 的学习、即时和延迟回忆以及识别能力显着下降。尽管 MND 的改善程度低于对照组，但这些子测试的表现随着时间的推移有所改善。当仅考虑“典型”ALS 患者时，这种关系并没有改变。与对照组相比，MND 患者的右侧海马旁回 (PhG) 变薄，并且随着时间的推移而逐渐变薄。根据整体情景记忆表现将记忆障碍的 MND 患者分组后，观察到双侧海马萎缩，其中右侧海马随着时间的推移而萎缩。在 MND 患者中，双侧海马萎缩与基线时的学习、回忆和识别能力受损有关。相比之下，左侧 PhG 稀疏与较差的学习表现相关。这些结果表明 MND 中的情景记忆障碍是一种常见的认知功能障碍。由于缺陷并没有随着病程而明显减少，因此该认知领域很可能早期参与疾病。海马和 PhG 的记忆表现依赖性萎缩为这些非运动皮质区域广泛参与疾病病理学提供了证据。