Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is associated with lower R2 relaxation rate: an ex-vivo MRI and pathology investigation

Limbic predominant age-related transactive response DNA binding protein 43 (TDP-43) encephalopathy neuropathological change (LATE-NC) is common in persons older than 80 years of age and is associated with cognitive decline and increased likelihood of dementia. The MRI signature of LATE-NC has not been fully determined. In this study, the association of LATE-NC with the transverse relaxation rate, R-2 , was investigated in a large number of community-based older adults. Cerebral hemispheres from 738 participants of the Rush Memory and Aging Project, Religious Orders Study, and Minority Aging Research Study, were imaged ex-vivo with multi-echo spin-echo MRI and underwent detailed neuropathologic examination. Voxel-wise analysis revealed a novel spatial pattern of lower R-2 for higher LATE-NC stage, controlling for other neuropathologies and demographics. This pattern was consistent with the distribution of LATE-NC in gray matter, and also involved white matter providing temporo-temporal, fronto-temporal, and temporo-basal ganglia connectivity. Furthermore, analysis at different LATE-NC stages showed that R-2 imaging may capture the general progression of LATE-NC, but only when TDP-43 inclusions extend beyond the amygdala. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study found an association between limbic predominant age-related transactive response DNA binding protein 43 (TDP-43) encephalopathy neuropathological change (LATE-NC) and the transverse relaxation rate R-2. R-2 imaging can capture the progression of LATE-NC, and the spatial pattern of lower R-2 is consistent with the distribution of LATE-NC in the brain.