Department of Neurology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Faculty of Philosophy, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
J Neurol. 2023 Aug;270(8):4031-4040. doi: 10.1007/s00415-023-11753-8. Epub 2023 May 8.
Previous studies have yielded inconsistent results about hippocampal involvement in non-demented patients with amyotrophic lateral sclerosis (ALS). We hypothesized that testing of memory-guided spatial navigation i.e., a highly hippocampus-dependent behaviour, might reveal behavioural correlates of hippocampal dysfunction in non-demented ALS patients.
We conducted a prospective study of spatial cognition in 43 non-demented ALS outpatients (11f, 32 m, mean age 60.0 years, mean disease duration 27.0 months, mean ALSFRS-R score 40.0) and 43 healthy controls (14f, 29 m, mean age 57.0 years). Participants were tested with a virtual memory-guided navigation task derived from animal research ("starmaze") that has previously been used in studies of hippocampal function. Participants were further tested with neuropsychological tests of visuospatial memory (SPART, 10/36 Spatial Recall Test), fluency (5PT, five-point test) and orientation (PTSOT, Perspective Taking/Spatial Orientation Test).
Patients successfully learned and navigated the starmaze from memory, both in conditions that forced memory of landmarks (success: patients 50.7%, controls 47.7%, p = 0.786) and memory of path sequences (success: patients 96.5%, controls 94.0%, p = 0.937). Measures of navigational efficacy (latency, path error and navigational uncertainty) did not differ between groups (p ≥ 0.546). Likewise, SPART, 5PT and PTSOT scores did not differ between groups (p ≥ 0.238).
This study found no behavioural correlate for hippocampal dysfunction in non-demented ALS patients. These findings support the view that the individual cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.
先前的研究对于非痴呆型肌萎缩性侧索硬化症（ALS）患者的海马体参与情况得出了不一致的结果。我们假设，对记忆引导的空间导航进行测试，即一种高度依赖海马体的行为，可能会揭示非痴呆型 ALS 患者海马体功能障碍的行为相关性。
我们对 43 名非痴呆型 ALS 门诊患者（11 名女性，32 名男性，平均年龄 60.0 岁，平均病程 27.0 个月，平均 ALSFRS-R 评分为 40.0）和 43 名健康对照者（14 名女性，29 名男性，平均年龄 57.0 岁）进行了前瞻性空间认知研究。参与者使用源自动物研究的虚拟记忆引导导航任务（“星型迷宫”）进行测试，该任务以前曾用于研究海马体功能。参与者还接受了神经心理学测试，包括视空间记忆（SPART，10/36 空间回忆测试）、流畅性（5PT，五点测试）和定向测试（PTSOT，视角转换/空间定向测试）。
患者成功地从记忆中学习并导航星型迷宫，无论是在强制记忆地标物的条件下（成功：患者 50.7%，对照组 47.7%，p=0.786）还是记忆路径序列的条件下（成功：患者 96.5%，对照组 94.0%，p=0.937）。两组的导航效率测量指标（潜伏期、路径错误和导航不确定性）无差异（p≥0.546）。同样，SPART、5PT 和 PTSOT 评分在两组之间也无差异（p≥0.238）。
本研究未发现非痴呆型 ALS 患者海马体功能障碍的行为相关性。这些发现支持这样一种观点，即 ALS 的个体认知表型可能与不同的疾病亚型有关，而不是同一潜在疾病的不同表现。
