Traumatic brain injury history is associated with earlier age of onset of Alzheimer disease

Christian LoBue, Hannah Wadsworth, Kristin Wilmoth, Matthew Clem, John Hart, Kyle B. Womack, Nyaz Didehbani, Laura H. Lacritz, Heidi C. Rossetti, C. Munro Cullum

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Objective: This study examined whether a history of traumatic brain injury (TBI) is associated with earlier onset of Alzheimer disease (AD), independent of apolipoprotein ε4 status (Apoe4) and gender. Method: Participants with a clinical diagnosis of AD (n = 7625) were obtained from the National Alzheimer’s Coordinating Center Uniform Data Set, and categorized based on self-reported lifetime TBI with loss of consciousness (LOC) (TBI+ vs. TBI−) and presence of Apoe4. ANCOVAs, controlling for gender, race, and education were used to examine the association between history of TBI, presence of Apoe4, and an interaction of both risk factors on estimated age of AD onset. Results: Estimated AD onset differed by TBI history and Apoe4 independently (p’s <.001). The TBI+ group had a mean age of onset 2.5 years earlier than the TBI− group. Likewise, Apoe4 carriers had a mean age of onset 2.3 years earlier than non-carriers. While the interaction was non-significant (p =.34), participants having both a history of TBI and Apoe4 had the earliest mean age of onset compared to those with a TBI history or Apoe4 alone (MDifference = 2.8 and 2.7 years, respectively). These results remained unchanged when stratified by gender. Conclusions: History of self-reported TBI can be associated with an earlier onset of AD-related cognitive decline, regardless of Apoe4 status and gender. TBI may be related to an underlying neurodegenerative process in AD, but the implications of age at time of injury, severity, and repetitive injuries remain unclear.

Original languageEnglish
Pages (from-to)85-98
Number of pages14
JournalClinical Neuropsychologist
Issue number1
StatePublished - Jan 2 2017


  • Alzheimer’s disease (AD)
  • National Alzheimer’s Coordinating Center (NACC)
  • age of onset
  • dementia
  • traumatic brain injury (TBI)


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