Diffusion tensor imaging studies of amyotrophic lateral sclerosis patients with various levels of cognitive impairment

Objective To characterize the brain microstructure changes of amyotrophic lateral sclerosis (ALS) patients with various levels of cognitive impairment as measured by diffusion tensor imaging (DTI). Methods A total of 55 ALS patients and 20 healthy controls (HC) were enrolled in the Department of Neurology of Peking Union Medical College Hospital From September 2013 to March 2017, and all participants underwent neuropsychological assessments and DTI scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n=27), ALS with cognitive impairment (ALS-Ci, n=17) and ALS-frontotemporal dementia (ALS-FTD, n=11) subgroups. Comparisons of voxel-based and atlas-based fractional anisotropy (FA) and mean diffusivity (MD) data were conducted among the four subgroups. Results In the voxel-based analyses, the FA showed significant differences in cingulate gyrus, corpus callosum, brain stem and cerebellum, and MD showed significant differences in bilateral frontal lobe, temporal lobe, cingulate gyrus, corpus callosum, and cerebellum among the four subgroups. Besides, when compared to ALS-Ci, ALS-Cn and HC groups in the order, the areas of involvement were larger and differences were more significant in ALS-FTD group. In the atlas-based analyses, the FA and MD of the corticospinal tracts revealed no difference within the patients groups, but decreased FA and increased MD were found compared to HC group. The ALS-FTD patients manifested widespread white matter fiber integrity damage and microstructure impairment in the extramotor areas compared to other three groups. Conclusion The brain white matter structural patterns of ALS patients correlate with their cognitive function, and there is a gradient of alterations across the ALS-Cn, ALS-Ci and ALS-FTD continuum. Key words: Amyotrophic lateral sclerosis; Cognition disorders; Frontotemporal dementia; Diffusion tensor imaging