Iazzolino Barbara, Palumbo Francesca, Moglia Cristina, Manera Umberto, Grassano Maurizio, Matteoni Enrico, Cabras Sara, Brunetti Maura, Vasta Rosario, Pagani Marco, Mora Gabriele, Canosa Antonio, Calvo Andrea, Chiò Adriano
ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Torino, Turin, Italy.
Division of Neurology 1, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza of Torino, Turin, Italy.
Ann Neurol. 2025 Jun;97(6):1122-1133. doi: 10.1002/ana.27194. Epub 2025 Feb 1.
The objective is to evaluate cognitive and behavioral progression and identify early predictors of these changes in a cohort of amyotrophic lateral sclerosis (ALS) patients.
A total of 161 ALS patients were tested at diagnosis (T0), and 107 were re-tested after 1 year (T1) using cognitive/behavioral tests. All patients underwent whole-genome sequencing, and 46 patients (ALS-normal cognition [CN]) underwent [18F]Fluorodeoxyglucose positron emission tomography.
Of the 161 patients, 107 were re-rested at T1; non-retested patients included 10 with frontotemporal dementia and 44 who were either non-testable or deceased. At T0, 67 patients (62.6%) were classified as ALS-CN, whereas 40 (38.4%) showed some degree of cognitive/behavioral impairment. Eighteen ALS-CN patients (26.9%) experienced cognitive decline at T1. Phenoconverters had lower baseline scores in letter fluency (Letter Fluency Test [FAS]) (p < 0.001), Edinburgh Cognitive and Behavioral ALS Screen (ECAS) verbal fluency score (p = 0.017). Both tests were independently predictive of phenoconversion in binary logistic regression models, with optimal cut-off scores of 28.75 and 14.2, with good sensitivity and specificity. Other predictors included older age, lower education, and ALS-related genetic variants. Phenoconverters were hypometabolic in the left temporal lobe. Thirteen (32.5%) of the 40 patients with cognitive impairment at T0 worsened by T1, with FAS (p = 0.02) and the ECAS verbal fluency score (p = 0.023) predicting further decline.
Approximately 30% of ALS patients experienced cognitive/behavioral decline within the first year after diagnosis. FAS and ECAS verbal fluency were predictive of cognitive phenoconversion. Our findings highlight the importance of early detection of at-risk individuals and the need for longitudinal cognitive assessments to monitor disease progression. ANN NEUROL 2025;97:1122-1133.
评估一组肌萎缩侧索硬化症（ALS）患者的认知和行为进展，并确定这些变化的早期预测指标。
共有161例ALS患者在诊断时（T0）接受测试，107例患者在1年后（T1）使用认知/行为测试进行重新测试。所有患者均接受全基因组测序，46例患者（ALS-正常认知[CN]）接受了[18F]氟脱氧葡萄糖正电子发射断层扫描。
161例患者中，107例在T1时进行了重新测试；未重新测试的患者包括10例额颞叶痴呆患者和44例无法测试或已死亡的患者。在T0时，67例患者（62.6%）被归类为ALS-CN，而40例（38.4%）表现出一定程度的认知/行为障碍。18例ALS-CN患者（26.9%）在T1时出现认知下降。表型转换者在字母流畅性（字母流畅性测试[FAS]）中的基线得分较低（p < 0.001），爱丁堡认知和行为ALS筛查（ECAS）言语流畅性得分较低（p = 0.017）。在二元逻辑回归模型中，这两项测试均独立预测表型转换，最佳截断分数分别为28.75和14.2，具有良好的敏感性和特异性。其他预测指标包括年龄较大、受教育程度较低和ALS相关基因变异。表型转换者左侧颞叶代谢减低。T0时40例认知障碍患者中有13例（32.5%）在T1时病情恶化，FAS（p = 0.02）和ECAS言语流畅性得分（p = 0.023）可预测病情进一步恶化。
约30%的ALS患者在诊断后的第一年内出现认知/行为下降。FAS和ECAS言语流畅性可预测认知表型转换。我们的研究结果强调了早期发现高危个体的重要性以及进行纵向认知评估以监测疾病进展的必要性。《神经病学年鉴》2025年；97:1122 - 1133。
