Association of TDP-43 Pathology With Domain-specific Literacy in Older Persons

Abstract

Background Low health and financial literacy may be an early behavioral manifestation of cognitive impairment, dementia, and accumulating Alzheimer’s pathology. However, there are limited studies investigating the behavioral features associated with hyperphosphorylated transactive response DNA-binding protein-43 (TDP-43), a common age-related pathology, and even fewer studies investigating the neurobiological basis underlying low literacy in aging. Objective To test the hypothesis that TDP-43 pathology is associated with lower literacy. Methods Data came from 293 community-based older persons who were enrolled in two ongoing studies of aging. Participants completed literacy and cognitive assessments, consented to brain donation, and underwent detailed neuropathological evaluation for AD and TDP-43. Linear regression models assessed the association of TDP-43 with literacy after adjusting for demographics, and AD pathology. Post-hoc pairwise comparisons examined whether the level of literacy differed by TDP-43 stage. Results TDP-43 pathology was associated with lower literacy (estimate=−3.16; SE=0.86; p<0.001), above and beyond demographics and AD pathology, and this association persisted even after additionally adjusting for global cognition (estimate=−1.53; SE=0.74; p=0.038). Further, literacy was lower among persons with neocortical TDP-43 pathology compared to those without TDP-43 pathology. Conclusion TDP-43 pathology is associated with lower health and financial literacy in old age, above and beyond AD pathology.