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, Francesca Palumbo, Cristina Moglia, Umberto Manera, Maurizio Grassano, Enrico Matteoni, Sara Cabras, Maura Brunetti, Rosario Vasta, Marco Pagani, Gabriele Mora, Antonio Canosa, Andrea Calvo, Adriano Chiò

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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.

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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.