Behavioral changes in early ALS correlate with voxel-based morphometry and diffusion tensor imaging

Background: Amyotrophic lateral sclerosis (ALS) is a multisystem disorder with impairment of frontotemporal functions such as cognition and behavior, but the behavioral changes associated with ALS are not well defined. Methods: Twenty-one consecutive patients with sporadic ALS and 21 control subjects participated in the study. The Frontal System Behavior Scale (FrSBe) was used to assess behavioral change. Voxel-based morphometry (VBM) and voxel-based analysis of diffusion tensor images (DTI) were performed to explore the associations of brain degeneration with behavior. All patients were evaluated before the notification of ALS. Results: FrSBe scores of ALS patients before notification were significantly increased compared to those of control subjects. Moreover, the FrSBe Apathy score of ALS patients significantly changed from pre- to post-illness (P < 0.001). The severity of apathy was significantly correlated with atrophy in the prefrontal cortex, especially in the orbitofrontal (P = 0.006) and dorsolateral prefrontal (P = 0.006) cortices in VBM, and in the right frontal gyrus (P < 0.001) in DTI. Conclusions: ALS patients exhibited apathy during the early course of the illness, the severity of which was significantly associated with frontal lobe involvement. These findings support the view that a continuum exits between ALS and frontotemporal dementia.