European journal of neurology · 2026
Recalibration of the Frontal Behavioural Inventory Cut-Off for Behavioural Screening in Amyotrophic Lateral Sclerosis.
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Iazzolino Barbara, Palumbo Francesca, Canosa Antonio, Callegaro Stefano, Passidomo Vita, Manera Umberto, Vasta Rosario, Matteoni Enrico, Cabras Sara, Pellegrino Giorgio, Maccabeo Alessandra, Moglia Cristina, Calvo Andrea, Chiò Adriano
Аннотация
OBJECTIVE: The Frontal Behavioural Inventory (FBI) was validated in behavioural-variant frontotemporal dementia (bvFTD) with a cut-off of 25. We tested whether this threshold is appropriate in amyotrophic lateral sclerosis (ALS), where behavioural change is milder and partly confounded by motor pathology.
METHODS: We analysed 506 ALS patients with a valid FBI assessment. Behavioural impairment was defined using two complementary reference standards, to minimise dependence on any single behavioural instrument: a consensus rule (pathology on ≥ 2 of three independent instruments: Edinburgh Cognitive and Behavioural ALS Screen, Frontal Systems Behaviour Scale, Beaumont Behavioural Inventory) and Latent Class Analysis. ROC analysis identified the Youden-optimal cut-off; agreement was quantified by Cohen's κ; internal validity was assessed by stratified 5-fold cross-validation. Total and subscale scores were analysed separately.
RESULTS: Among 345 complete-case patients, 24.6% met criteria for behavioural impairment. The FBI total discriminated impairment well (AUC 0.855, 95% CI 0.806-0.898). The Youden-optimal cut-off was FBI ≥ 9 (sensitivity 0.87, specificity 0.74), whereas the legacy cut-off of 25 showed sensitivity 0.22. Subscale recalibration yielded cut-offs of FBI-Apathy ≥ 7 (AUC 0.808) and FBI-Disinhibition ≥ 4 (AUC 0.851).
CONCLUSIONS: In ALS, the bvFTD-derived threshold of 25 misses most patients with behavioural involvement. FBI ≥ 9 is a promising candidate ALS-specific screening threshold, with scores ≥ 15 indicating a higher probability of behavioural involvement; exploratory subscale thresholds of ≥ 7 for Apathy and ≥ 4 for Disinhibition are also proposed. These cut-offs substantially improve sensitivity while maintaining acceptable specificity, but require prospective external validation before replacing current practice.
METHODS: We analysed 506 ALS patients with a valid FBI assessment. Behavioural impairment was defined using two complementary reference standards, to minimise dependence on any single behavioural instrument: a consensus rule (pathology on ≥ 2 of three independent instruments: Edinburgh Cognitive and Behavioural ALS Screen, Frontal Systems Behaviour Scale, Beaumont Behavioural Inventory) and Latent Class Analysis. ROC analysis identified the Youden-optimal cut-off; agreement was quantified by Cohen's κ; internal validity was assessed by stratified 5-fold cross-validation. Total and subscale scores were analysed separately.
RESULTS: Among 345 complete-case patients, 24.6% met criteria for behavioural impairment. The FBI total discriminated impairment well (AUC 0.855, 95% CI 0.806-0.898). The Youden-optimal cut-off was FBI ≥ 9 (sensitivity 0.87, specificity 0.74), whereas the legacy cut-off of 25 showed sensitivity 0.22. Subscale recalibration yielded cut-offs of FBI-Apathy ≥ 7 (AUC 0.808) and FBI-Disinhibition ≥ 4 (AUC 0.851).
CONCLUSIONS: In ALS, the bvFTD-derived threshold of 25 misses most patients with behavioural involvement. FBI ≥ 9 is a promising candidate ALS-specific screening threshold, with scores ≥ 15 indicating a higher probability of behavioural involvement; exploratory subscale thresholds of ≥ 7 for Apathy and ≥ 4 for Disinhibition are also proposed. These cut-offs substantially improve sensitivity while maintaining acceptable specificity, but require prospective external validation before replacing current practice.