Association of remote mild traumatic brain injury with cortical amyloid burden in clinically normal older adults

Breton M. Asken, William G. Mantyh, Renaud La Joie, Amelia Strom, Kaitlin B. Casaletto, Adam M. Staffaroni, Alexandra C. Apple, Cutter A. Lindbergh, Leonardo Iaccarino, Michelle You, Harli Grant, Corrina Fonseca, Charles Windon, Kyan Younes, Jeremy Tanner, Gil D. Rabinovici, Joel H. Kramer, Raquel C. Gardner

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


We investigated whether clinically normal older adults with remote, mild traumatic brain injury (mTBI) show evidence of higher cortical Aβ burden. Our study included 134 clinically normal older adults (age 74.1 ± 6.8 years, 59.7% female, 85.8% white) who underwent Aβ positron emission tomography (Aβ-PET) and who completed the Ohio State University Traumatic Brain Injury Identification questionnaire. We limited participants to those reporting injuries classified as mTBI. A subset (N = 30) underwent a second Aβ-PET scan (mean 2.7 years later). We examined the effect of remote mTBI on Aβ-PET burden, interactions between remote mTBI and age, sex, and APOE status, longitudinal Aβ accumulation, and the interaction between remote mTBI and Aβ burden on memory and executive functioning. Of 134 participants, 48 (36%) reported remote mTBI (0, N = 86; 1, N = 31, 2+, N = 17; mean 37 ± 23 years since last mTBI). Effect size estimates were small to negligible for the association of remote mTBI with Aβ burden (p =.94, η2 < 0.01), and for all interaction analyses. Longitudinally, we found a non-statistically significant association of those with remote mTBI (N = 11) having a faster rate of Aβ accumulation (B = 0.01, p =.08) than those without (N = 19). There was no significant interaction between remote mTBI and Aβ burden on cognition. In clinically normal older adults, history of mTBI is not associated with greater cortical Aβ burden and does not interact with Aβ burden to impact cognition. Longitudinal analyses suggest remote mTBI may be associated with more rapid cortical Aβ accumulation. This finding warrants further study in larger and more diverse samples with well-characterized lifelong head trauma exposure.

Original languageEnglish (US)
Pages (from-to)2417-2425
Number of pages9
JournalBrain Imaging and Behavior
Issue number5
Early online dateJan 11 2021
StatePublished - Oct 2021
Externally publishedYes

Bibliographical note

Funding Information:
We thank the following funding sources that have supported our work: UCSF ADRC (NIA P50AG023501 and P30AG062422; PI: Bruce Miller), NIH-NIA (R01 AG045611) to GDR; NIH-NIA (R01(s) AG032289 and AG048234) and Larry L. Hillblom Network Grant (2014-A-004-NET) to JHK; NIH-NINDS (K23 NS095755), American Federation for Aging Research, and Global Brain Health Institute to RCG; NIH-NIA (K23 AG058752) to KBC; NIH-NIA (K23 AG061253) and Larry L. Hillblom Fellowship (2018-A-025-FEL) to AMS; NIH-NIA (K99AG065501) and Alzheimer’s Association (AARF-16-443577) to RLJ; and the Robert W. Katzman Fellowship Training Grant through the American Academy of Neurology in conjunction with the American Brain Foundation and Alzheimer’s Association to WGM.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.


  • Aging
  • Amyloid
  • Concussion
  • Dementia
  • Neurodegenerative
  • PET
  • Traumatic brain injury


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