Brain Morphometry Patterns in the Presence of Alzheimer’s Disease and/or LATE Neuropathologic Changes

Alzheimer’s disease neuropathologic change (ADNC) and limbic-predominant age-related transactive response DNA-binding protein 43 kDa (TDP-43) encephalopathy neuropathologic change (LATENC) are common in older adults, yet differences in brain morphometry patterns when one or both pathologies are present remain unclear. We used deformation-based morphometry on ex vivo MRI from 912 community-based older adults to compare groups with or without ADNC and/or LATENC. AD+LATE- and AD-LATE+ groups showed less tissue in the medial temporal lobe than AD-LATE-. The AD+LATE+ group had less tissue in temporal, frontal, and parietal lobes. The AD-LATE+ group exhibited smaller anterior hippocampi than the AD+LATE- group. These findings were less pronounced in individuals without dementia. Increments in LATENC stages were associated with smaller hippocampi than increments in ADNC severity, independent of the severity of comorbid ADNC or LATENC, respectively. These findings reveal distinct and overlapping brain morphometry patterns associated with ADNC and/or LATENC, with possible implications for diagnosis in older adults.

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Recommended citation: Saifullah K, Ridwan AR, Evia AM, et al. Brain morphometry patterns in the presence of Alzheimer’s disease and/or LATE neuropathologic changes. Alzheimer’s Dement. 2026;22:e71719. doi:10.1002/alz.71719.
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