Frequency and Early Predictors of Cognitive Deterioration in Amyotrophic Lateral Sclerosis: A Longitudinal Population-Based Study

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-02-01 DOI:10.1002/ana.27194

Barbara Iazzolino PsyD, Francesca Palumbo MD, Cristina Moglia MD, PhD, Umberto Manera MD, PhD, Maurizio Grassano MD, PhD, Enrico Matteoni MD, Sara Cabras MD, Maura Brunetti BsC, Rosario Vasta MD, PhD, Marco Pagani MD, Gabriele Mora MD, Antonio Canosa MD, PhD, Andrea Calvo MD, PhD, FAAN, FEAN, Adriano Chiò MD, FAAN

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引用次数: 0

Abstract

Objective

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.

Methods

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.

Results

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.

Interpretation

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

查看原文本刊更多论文

肌萎缩侧索硬化症患者认知退化的频率和早期预测因素：一项基于人群的纵向研究。

目的：目的是评估肌萎缩侧索硬化症（ALS）患者的认知和行为进展，并确定这些变化的早期预测因素。方法：161例ALS患者在诊断时（T0）进行认知/行为测试，107例患者在1年后（T1）再次进行认知/行为测试。所有患者均进行全基因组测序，46例（als -认知正常[CN]）患者进行了[18F]氟脱氧葡萄糖正电子发射断层扫描。结果：161例患者中，107例在T1时再次休息；未重新检测的患者包括10名额颞叶痴呆患者和44名无法检测或已死亡的患者。在T0时，67例（62.6%）患者被归类为ALS-CN，而40例（38.4%）患者表现出一定程度的认知/行为障碍。18例ALS-CN患者（26.9%）在T1时出现认知能力下降。表型转换者在字母流畅性（字母流畅性测试[FAS]）方面的基线得分较低(p)。解释：大约30%的ALS患者在诊断后的一年内出现认知/行为下降。FAS和ECAS语言流畅性可预测认知表型转化。我们的研究结果强调了早期发现高危个体的重要性，以及对疾病进展进行纵向认知评估的必要性。Ann neurol 2025。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.