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September 06, 2023Research Article

Associations Between Traumatic Brain Injury and Cognitive Decline Among Older Veteran Men - A Twin Study

View ORCID ProfileMarianne Chanti-Ketterl, View ORCID ProfileCarl F Pieper, Kristine Yaffe, Brenda L Plassman
First published September 6, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207819
Marianne Chanti-Ketterl
1Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC
2Center for Aging and Human Development, Duke University Medical Center, Durham, NC
PhD, MSPH
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  • ORCID record for Marianne Chanti-Ketterl
  • For correspondence: marianne.chanti-ketterl@duke.edu
Carl F Pieper
2Center for Aging and Human Development, Duke University Medical Center, Durham, NC
3Dept. Biostatistics & Bioinformatics
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  • ORCID record for Carl F Pieper
Kristine Yaffe
45Departments of Psychiatry and Behavioral Sciences, Neurology and Epidemiology and Biostatistics, University of California, San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA
MD
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Brenda L Plassman
2Center for Aging and Human Development, Duke University Medical Center, Durham, NC
5Department of Neurology, Duke University Medical Center, Durham, NC
PhD
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Citation
Associations Between Traumatic Brain Injury and Cognitive Decline Among Older Veteran Men - A Twin Study
Marianne Chanti-Ketterl, Carl F Pieper, Kristine Yaffe, Brenda L Plassman
Neurology Sep 2023, 10.1212/WNL.0000000000207819; DOI: 10.1212/WNL.0000000000207819

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Abstract

Background: Traumatic brain injuries (TBI) are associated with increased risk of dementia, but whether lifetime TBI influences cognitive trajectories in later life is less clear. Cognitive interventions post TBI may improve cognitive trajectories and delay dementia. Since twins share many genes and environmental factors, we capitalize on the twin-study design to examine the association between lifetime TBI and cognitive decline.

Methods: Participants were members of the National Academy of Sciences National Research Council’s Twin Registry of male veterans of World-War-II with self or proxy reported history of TBI and with up to four observations over 12 years of the modified Telephone Interview for Cognitive Status (TICS-m). We used linear random effects mixed models to analyze the association between TBI and TICS-m in the full sample and among co-twins discordant for TBI. Additional TBI predictor variables included: number of TBI, severity (loss of consciousness [LOC]), age first TBI (age <25 vs. 25+ [older age TBI])). Models were adjusted for age (centered at 70-years), age-squared, education, wave, twin pair, lifestyle behaviors and medical conditions.

Results: Of 8,662 participants, 25% reported TBI. History of any TBI (β=-0.56, CI95% -0.73, -0.39), TBI with LOC (β=-0.51, CI95% -0.71, -0.31), and older-age TBI (β=-0.66, CI95% -0.90, -0.42) were associated with lower TICS-m scores at age-70. TBI with LOC (β=-0.03, CI95% -0.05, -0.001), more than one TBI (β=-0.05, CI95% -0.09, -0.002,), and older age TBI (β=-0.06, CI95% -0.09, -0.03) were associated with faster cognitive decline. Among monozygotic pairs discordant for TBI (589 pairs), a history of any TBI (β=-0.55, CI95% -0.91, -0.19) and having older age TBI (β=-0.74, CI95% -1.22, -0.26,) was associated with lower TICS-m scores at age-70. Those with more than one TBI (β=-0.13, CI95% -0.23, -0.03) and older age TBI (β=-0.07, CI95% -0.13, -0.002) showed greater cognitive decline compared to their cotwin without TBI.

Discussion: These findings support an association on the impact of TBI on cognitive score and the rapidity of cognitive decline in later life. The results in monozygotic pairs, who share all genes and many exposures particularly in early life, provide additional evidence of a causal relationship between TBI and poorer late life cognitive outcomes.

  • Received March 24, 2023.
  • Accepted in final form July 10, 2023.
  • © 2023 American Academy of Neurology

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