Executive Dysfunction and Disability in SPMS: Predictive Value of the Frontal Assessment Battery in the UCLH MS-STAT2 Cohort

Introduction: Cognitive impairment is common in secondary progressive multiple sclerosis (SPMS), with executive dysfunction disproportionately so. The frontal assessment battery (FAB) is a bedside test assessing executive function. This study explores the distribution of FAB scores in a large SPMS cohort and their associations with disability. Methods: Data were analysed from 294 participants in a cognitive substudy of the MS-STAT2 trial (NCT03387670). Associations between baseline FAB scores, ambulation status (Expanded Disability Status Scale [EDSS] < 6.0 vs. ≥ 6.0) and other disability measures were assessed using generalised linear models, adjusting for age, education, gender and disease duration. FAB performance was also compared against other cognitive tests (SDMT, CVLT-II, BVMT-R). Results: 23.8% of participants scored the FAB maximum of 18; 29.9% scored below the clinical threshold of 16. FAB scores showed moderate correlations with SDMT (ρ = 0.46), CVLT-II (ρ = 0.36) and BVMT-R (ρ = 0.43), and participants scoring < 16 were significantly more likely to be impaired across these cognitive domains (p < 0.001). Lower baseline FAB scores were significantly associated with higher EDSS, slower T25FW and reduced manual dexterity (9HPT) (all p < 0.005) at baseline and longitudinally, with performance comparable to other validated cognitive tests. Conclusions: We present a large cohort of FAB scores in the SPMS population. Lower FAB scores are associated with both concurrent and future disability and may offer a scalable tool for identifying individuals at greater risk of progression and a robust trial outcome measure.