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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  &lt; 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.

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