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

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