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

Kapasi, Alifiya PhD*,†; Yu, Lei PhD*,‡; Stewart, Christopher C. PhD§; Schneider, Julie A. MD, MS*,†,‡; Bennett, David A. MD*,‡; Boyle, Patricia A. PhD*,∥

Alzheimer Disease & Associated Disorders: October–December 2019 - Volume 33 - Issue 4 - p 315–320
doi: 10.1097/WAD.0000000000000334
Original Articles

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.

*Rush Alzheimer’s Disease Center

Departments of Pathology (Neuropathology)

Neurological Sciences

Behavioral Sciences, Rush University Medical Center, Chicago, IL

§Department of Neurology, Indiana University School of Medicine, Indianapolis, IN

A.K., L.Y., J.A.S., P.A.B.: involved in conception, design, and execution of the project. A.K.: wrote the first draft. L.Y., C.C.S., J.A.S., D.A.B., and P.A.B.: reviewed and critiqued subsequent manuscript drafts.

Supported by the National Institute on Aging (grant number P30AG010161, R01AG017917, R01AG15819, R01AG033678, R01AG034374, R01AG042210).

The authors declare no conflicts of interest.

Reprints: Alifiya Kapasi, PhD, Rush Alzheimer’s Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL 60612 (e-mail:

Received March 20, 2019

Accepted May 17, 2019

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