Frontotemporal white matter changes in amyotrophic lateral sclerosis.

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Cognitive dysfunction, particularly verbal fluency deficits, is observed in amyotrophic lateral sclerosis (ALS) patients without dementia.
• Functional imaging studies (PET) in ALS patients with verbal fluency deficits show abnormalities in frontotemporal regions.

Purpose of the Study:

• To investigate the underlying structural cerebral changes in non-demented ALS patients with verbal fluency deficits using MRI.
• To compare white and grey matter densities between cognitively impaired ALS patients (ALSi), cognitively unimpaired ALS patients (ALSu), and healthy controls.

Main Methods:

• Automated volumetric voxel-based analysis of structural MRI scans.
• Comparison of grey and white matter densities between ALSi (n=11), ALSu (n=12), and control (n=12) groups.
• Assessment of cognitive function using the Written Verbal Fluency Test.

Main Results:

• The ALSi group showed significantly reduced white matter volume in extensive frontotemporal motor and non-motor regions compared to controls.
• ALSi patients exhibited executive and memory dysfunction, correlating with white matter abnormalities.
• The ALSu group had less extensive white matter reductions in frontal regions, and white matter volume correlated with memory test performance.
• No significant grey matter volume reductions were found in either ALS group compared to controls.

Conclusions:

• Structural white matter abnormalities in frontotemporal regions are associated with cognitive deficits in non-demented ALS patients.
• These findings suggest that extra-motor structural changes may be present in ALS even without overt cognitive impairment.
• The results support a continuum of extra-motor cerebral and cognitive changes in ALS.