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

Alzheimer Dis Assoc Disord. 2019 Oct-Dec;33(4):315-320. doi: 10.1097/WAD.0000000000000334.


Background: Low health and financial literacy may be an early behavioral manifestation of cognitive impairment, dementia, and accumulating Alzheimer 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.

Materials and methods: Data came from 293 community-based older persons who were enrolled in 2 ongoing studies of aging. Participants completed literacy and cognitive assessments, consented to brain donation, and underwent detailed neuropathologic evaluation for Alzheimer disease (AD) and TDP-43. Linear regression models assessed the association of TDP-43 with literacy after adjusting for demographics, and AD pathology. Posthoc 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 with those without TDP-43 pathology.

Conclusions: TDP-43 pathology is associated with lower health and financial literacy in old age, above and beyond AD pathology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Brain / pathology
  • Cognitive Dysfunction / pathology*
  • Cohort Studies
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • Literacy*
  • Longitudinal Studies
  • Male
  • TDP-43 Proteinopathies / pathology*


  • DNA-Binding Proteins
  • TARDBP protein, human