Associations Between Traumatic Brain Injury and Cognitive Decline Among Older Male Veterans: A Twin Study

Background and objectives: Traumatic brain injuries (TBIs) are associated with increased risk of dementia, but whether lifetime TBI influences cognitive trajectories in later life is less clear. Cognitive interventions after TBI may improve cognitive trajectories and delay dementia. Because 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 4 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 TBIs, severity (loss of consciousness [LOC]), and age of first TBI (age <25 vs 25+ years [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, 95% CI -0.73 to -0.39), TBI with LOC (β = -0.51, 95% CI -0.71 to -0.31), and older age TBI (β = -0.66, 95% CI -0.90 to -0.42) were associated with lower TICS-m scores at 70 years. TBI with LOC (β = -0.03, 95% CI -0.05 to -0.001), more than one TBI (β = -0.05, 95% CI -0.09 to -0.002,), and older age TBI (β = -0.06, 95% CI -0.09 to -0.03) were associated with faster cognitive decline. Among monozygotic pairs discordant for TBI (589 pairs), history of any TBI (β = -0.55, 95% CI -0.91 to -0.19) and older age TBI (β = -0.74, 95% CI -1.22 to -0.26) were associated with lower TICS-m scores at 70 years. Those with more than one TBI (β = -0.13, 95% CI -0.23 to -0.03) and older age TBI (β = -0.07, 95% CI -0.13 to -0.002) showed greater cognitive decline compared with their co-twin without TBI.

Discussion: These findings support an association of the effect 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.