Correlation of frontal atrophy with behavioral changes in amyotrophic lateral sclerosis

Background Recent studies have linked cognitive impairment in amyotrophic lateral sclerosis to frontotemporal pathology. Aim We examined possible associations between behavior changes and regional gray matter volume in early amyotrophic lateral sclerosis, and assessed whether the volume changes were independent of physical impairments. Methods A total of 17 amyotrophic lateral sclerosis patients with Mini‐Mental State Examination score ≥ 24, no need for assistance in daily life and normal respiratory tests (respiratory function test and arterial blood gas analytes), and 11 age‐matched controls underwent structural magnetic resonance imaging. Behavioral changes were assessed with family‐rating Frontal Systems Behavior Scale. We applied voxel‐based morphometry to investigate the correlation between the Frontal Systems Behavior Scale and gray matter volume, and assessed the correlation of volume with amyotrophic lateral sclerosis Functional Rating Scale and respiratory tests. Results Current Frontal Systems Behavior Scale scores were significantly higher than retrospective scores assessing the status before onset, most notably in apathy. The volumes of right middle and left medial frontal gyri in amyotrophic lateral sclerosis were negatively correlated with the Frontal Systems Behavior Scale, whereas they were not correlated with amyotrophic lateral sclerosis Functional Rating Scale and respiratory tests. The volume of the right frontal cluster, but not the left medial frontal cluster, was significantly smaller than that of controls. Conclusions Regional atrophy within the frontal lobe was associated with behavioral dysfunction in early amyotrophic lateral sclerosis, this association was independent of physical factors.