Disease progression in probable limbic-predominant age-related TDP-43 encephalopathy

Limbic-predominant age-related transactive response DNA-binding protein of 43 kDa (TDP-43) encephalopathy (LATE) is confirmed in post mortem examination by TDP-43 pathology. Applying certain criteria, we examined cognitive trajectories in probable LATE and Alzheimer's disease (AD) participants compared with cognitively normal (CN) participants.

From the Alzheimer's Disease Neuroimaging Initiative, 108 individuals were classified into AD, probable LATE, or CN groups based on cognitive status, amyloid beta/tau biomarkers, and hippocampal volume. Cognition was assessed prospectively after baseline.

Both probable LATE and AD showed faster decline than CN participants. The magnitude of decline was generally greater in AD than in probable LATE across cognitive domains. Annual rates of change were 0.81 and 2.08 for probable LATE and AD, respectively, on the Alzheimer's Disease Assessment Scale-Cognitive Subscale, 0.24 and 0.36 on the Clinical Dementia Rating Scale-Sum of Boxes, -0.50 and -0.72 on Logical Memory II, and 5.83 and 10.98 on Trail Making Test Part B.

These findings support the identification of probable LATE clinically and may inform diagnostic strategies and therapeutic trial design.