Limbic-predominant Age-related TDP-43 Encephalopathy and Distinct Longitudinal Profiles of Domain-specific Literacy

Purpose: Emerging evidence suggests that limbic-predominant age-related TAR DNA-binding protein-43 (TDP-43) encephalopathy impacts domain-specific literacy, a complex ability not assessed in traditional cognitive evaluations. We examined longitudinal profiles of financial and health literacy in relation to limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC).

Participants: A total of 275 community-dwelling older persons who had completed annual literacy assessments, died and undergone brain autopsy.

Methods: Financial and health literacy was assessed using a 32-item instrument. Latent class mixed effects models identified groups of individuals with distinct longitudinal literacy profiles. Regression models examined group differences in 9 common age-related neuropathologies assessed via uniform structured neuropathologic evaluations.

Results: Two distinct literacy profiles emerged. The first group (N=121, 44%) had higher level of literacy at baseline, slower decline and less variabilities over time. The second group (N=154, 56%) had lower level of literacy at baseline, faster decline, and greater variabilities. Individuals from the latter group were older, with fewer years of education and more female. They also had higher burdens of Alzheimer disease and LATE-NC. The group association with Alzheimer disease was attenuated and no longer significant after controlling for cognition. By contrast, the association with LATE-NC persisted.

Conclusion: Limbic-predominant age-related TDP-43 encephalopathy is uniquely associated with distinct longitudinal profiles of financial and health literacy in old age.