Clinical and Imaging Features of Sporadic and Genetic Frontotemporal Lobar Degeneration TDP-43 A and B.

Objective: Certain frontotemporal lobar degeneration subtypes, including TDP-A and B, can either occur sporadically or in association with specific genetic mutations. It is uncertain whether syndromic or imaging features previously associated with these patient groups are subtype or genotype specific. Our study sought to discern the similarities and differences between sporadic and genetic TDP-A and TDP-B.

Methods: We generated individual atrophy maps and extracted mean atrophy scores for regions of interest-frontotemporal, occipitoparietal, thalamus, and cerebellum-in 54 patients with FTLD-TDP types A or B. We calculated asymmetry as the absolute difference in atrophy between right and left frontotemporal regions, and dorsality as the difference in atrophy between dorsal and ventral frontotemporal regions. We used ANCOVAs adjusted for disease severity to compare atrophy extent or imbalance, neuropsychological tests, and behavioral measures.

Results: For some regions, volumetric differences were found either between TDP subtypes (e.g., worse occipitoparietal and cerebellum atrophy in TDP-A than B), or within subtypes depending on genetic status (e.g., worse thalamic and occipitoparietal atrophy in C9orf72-associated TDP-B than sporadic TDP-B). While progranulin mutation-associated TDP-A and sporadic TDP-A cases can be strongly asymmetric, TDP-A and TDP-B associated with C9orf72 tended to be symmetric. TDP-A was more dorsal in atrophy than TDP-B, regardless of genetic status.

Interpretation: While some neuroimaging features are FTLD-TDP subtype-specific and do not significantly differ based on genotype, other features differ between sporadic and genetic forms within the same subtype and could decrease accuracy of classification algorithms that group genetic and sporadic cases.