Comparing brain structural MRI and metabolic FDG-PET changes in patients with ALS-FTD: 'the chicken or the egg?' question

Objective Our previous voxel based morphometry (VBM) studies in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (ALS-FTD) showed reduced motor and extramotor grey matter (GM) volume when compared to neurological controls. However, erroneously high GM values can result because VBM analysis includes both cortical gyri and sulci as a single GM region. In addition, the relationship between structural and functional changes is unknown. Therefore, we determined whether GM volumetric changes seen in patients with ALS-FTD were due to changes in cortical thickness, area or both, and compared these structural changes with metabolic changes as revealed by positron emission tomography (PET). Methods T1-weighted MRIs were obtained in unaffected neurological controls and in patients with ALS-FTD; the latter also underwent PET imaging. We assessed brain GM structural changes using VBM and cortical thickness, and metabolic changes using PET images. Significant (p<0.05) reductions in GM volume and cortical thickness were observed in motor and extramotor regions in patients with ALS-FTD compared to controls. No significant difference in cortical surface area was observed in any of the brain regions. Results Significant (p<0.05) reductions in cerebral glucose metabolism rate were observed in brain regions where structural changes were also observed. Significant reductions primarily in cortical thickness were the likely reason for decreased GM volume in ALS-FTD. Conclusions Metabolic changes corresponded well with structural changes in motor and extramotor areas, and sometimes occurred even in the absence of GM volume reduction. Coincident structural and functional GM changes suggest that neurodegeneration may occur as neuronopathy in patients with ALS-FTD.