Italian reference values and brain correlates of verbal fluency index - vs standard verbal fluency test - to assess executive dysfunction in ALS.

Objectives: In amyotrophic lateral sclerosis (ALS), verbal fluency index (V fi ) is used to investigate fluency accounting for motor impairment. This study has three aims: (1) to provide V fi reference values from a cohort of Italian healthy subjects; (2) to assess the ability of V fi reference values ( vs standard verbal fluency test [VFT]) in distinguishing ALS patients with and without executive dysfunction; and (3) to investigate the association between V fi and brain structural features of ALS patients. Methods: We included 180 healthy subjects and 157 ALS patients who underwent neuropsychological assessment, including VFT and V fi , and brain MRI. Healthy subjects were split into four subgroups according to sex and education. For each subgroup, we defined the 95th percentile of V fi as the cutoff. In ALS, the distributions of "abnormal" cases based on V fi and standard VFT cutoffs were compared using Fisher's exact test. Using quantile regressions in patients, we assessed the association between V fi and VFT scores, separately, with gray matter volumes and white matter (WM) tract integrity. Results: Applying V fi and VFT cutoffs, 9 and 13% of ALS cases, respectively, had abnormal scores ( p  < 0.001). In ALS, while higher V fi scores were associated with WM changes of callosal fibers linking supplementary motor area, lower VFT performances related to corticospinal tract alterations. Discussion: We provided Italian reference values for the spoken V fi . Compared to VFT, V fi s are critical to disentangle motor and cognitive deficits in ALS. In patients, abnormal V fi s were associated with damage to WM tracts specifically involved in ideational information processing.