Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is associated with abnormalities in white matter structural integrity and connectivity: An ex-vivo diffusion MRI and pathology investigation.

Limbic predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is common in older adults and is associated with neurodegeneration, cognitive decline and dementia. In this MRI and pathology investigation we tested the hypothesis that LATE-NC is associated with abnormalities in white matter structural integrity and connectivity of a network of brain regions typically harboring TDP-43 inclusions in LATE, referred to here as the "LATE-NC network". Ex-vivo diffusion MRI and detailed neuropathological data were collected on 184 community-based older adults. Linear regression revealed an independent association of higher LATE-NC stage with lower diffusion anisotropy in a set of white matter connections forming a pattern of connectivity that is consistent with the stereotypical spread of this pathology in the brain. Graph theory analysis revealed an association of higher LATE-NC stage with weaker integration and segregation in the LATE-NC network. Abnormalities were significant in stage 3, suggesting that they are detectable in later stages of the disease. Finally, LATE-NC network abnormalities were associated with faster cognitive decline, specifically in episodic and semantic memory.

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, R2, 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 R2 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 R2 imaging may capture the general progression of LATE-NC, but only when TDP-43 inclusions extend beyond the amygdala.

Development and evaluation of a high performance T1-weighted brain template for use in studies on older adults.

Τhe accuracy of template-based neuroimaging investigations depends on the template's image quality and representativeness of the individuals under study. Yet a thorough, quantitative investigation of how available standardized and study-specific T1-weighted templates perform in studies on older adults has not been conducted. The purpose of this work was to construct a high-quality standardized T1-weighted template specifically designed for the older adult brain, and systematically compare the new template to several other standardized and study-specific templates in terms of image quality, performance in spatial normalization of older adult data and detection of small inter-group morphometric differences, and representativeness of the older adult brain. The new template was constructed with state-of-the-art spatial normalization of high-quality data from 222 older adults. It was shown that the new template (a) exhibited high image sharpness, (b) provided higher inter-subject spatial normalization accuracy and (c) allowed detection of smaller inter-group morphometric differences compared to other standardized templates, (d) had similar performance to that of study-specific templates constructed with the same methodology, and (e) was highly representative of the older adult brain.