Brain Morphometry Patterns in the Presence of Alzheimer’s and/or Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE) Neuropathology

Alzheimer’s disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATENC) are common in older adults, yet our understanding of the differences in brain morphometry patterns when one or both pathologies are present is still incomplete. We used voxel-wise deformation-based morphometry (DBM) on ex-vivo MRI from 912 community-based older adults to compare brain morphometry across neuropathological groups defined by the presence or absence of ADNC and LATENC. Group comparisons were performed using permutation-based linear regression, adjusting for other pathologies and demographics. Both the AD+LATE- and AD-LATE+ groups showed less tissue in the medial temporal lobe compared to the AD-LATE- group. The AD+LATE+ group demonstrated less tissue across more regions in the temporal, frontal, and parietal lobes. The AD-LATE+ group exhibited a smaller anterior hippocampus than the AD+LATE- group. The above findings were similar but less pronounced in individuals without dementia. Furthermore, increments in LATENC stages (0, 1, 2, 3) were associated with smaller hippocampi than increments in ADNC severity (none, low, intermediate, high), independent of the severity of comorbid ADNC or comorbid LATENC, respectively. These findings reveal similarities and differences in brain morphometry patterns in the presence of ADNC and/or LATENC, with implications for diagnosis in older adults.

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