Involvement of the caudate nucleus head and its networks in sporadic amyotrophic lateral sclerosis-frontotemporal dementia continuum

Abstract

We investigated common structural and network changes across the sporadic amyotrophic lateral sclerosis (ALS)-frontotemporal dementia (FTD) continuum. Based on cluster analysis using the frontotemporal assessment battery, 51 patients with sporadic ALS were subdivided into three groups: 25 patients with ALS with cognitive deficiency (ALS-CD); seven patients who satisfied FTD criteria (ALS-FTD), and 19 patients with ALS with normal cognitive function (ALS-NC). Compared with the controls, gray matter images from patients with ALS-FTD showed atrophic changes in the following order of severity: caudate head, medial frontal gyrus, thalamus, amygdala, putamen, and cingulate gyrus (peak level, uncorrected p < 0.001). The caudate head was significant at the cluster level using FWE correction (p < 0.05). Diffusion tensor imaging with tract-based spatial statistics revealed white matter changes in the areas surrounding the caudate head, the internal capsule, and the anterior horn of the lateral ventricle in the ALS-CD and ALS-FTD. Probabilistic diffusion tractography showed a significant decrease in structural connectivity between the caudate head and the dorsomedial frontal cortex and the lateral orbitofrontal cortex, even in the ALS-NC. Our results indicated that the caudate head and its networks were the most vulnerable to lesion in sporadic ALS-FTD-spectrum patients associated with cognitive decline with FTD features.

Key words:

• Voxel-based morphometry (VBM)
• tract-based spatial statistics (TBSS)
• probabilistic diffusion tractography
• amyotrophic lateral sclerosis (ALS)
• frontotemporal dementia (FTD)

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Acknowledgements

This work was supported by grants-in-aid from the Research Committee of Central Nervous System Degenerative Diseases by the Ministry of Health, Labour, and Welfare, and from Integrated Research on Neuropsychiatric Disorders, a project carried out under the Strategic Research for Brain Sciences by the Ministry of Education, Culture, Sports, Science, and Technology of Japan. This work was also supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and a grant-in-aid for scientific research on Innovative Areas (Brain Protein Aging and Dementia Control) from MEXT.

Declaration of interest

The authors declare no conflicts of interest.

Supplementary material available online