Affiliations: [a] Psychology Department, The Ohio State University, Columbus, OH, USA
| [b] Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA
| [c] Chronic Brain Injury Initiative, The Ohio State University, Columbus, OH, USA
Correspondence:
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Correspondence to: Jasmeet P. Hayes, PhD, Psychology Department, The Ohio State University, Psychology Building, 1835 Neil Avenue, Columbus, OH 43210, USA. Tel.: +614 292 3300; E-mail: [email protected].
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abstract: Background:Traumatic brain injury (TBI) may confer risk for Alzheimer’s disease (AD) through amyloid-β (Aβ) overproduction. However, the relationship between TBI and Aβ levels in cerebrospinal fluid (CSF) remains unclear. Objective:To explore whether Aβ overproduction is implicated in the relationship between TBI and AD, we compared CSF levels of Aβ in individuals with a TBI history versus controls (CTRLs) and related CSF Aβ levels to cognitive markers associated with preclinical AD. Methods:Participants were 112 non-impaired Veterans (TBI = 56, CTRL = 56) from the Alzheimer’s Disease Neuroimaging Initiative-Department of Defense database with available cognitive data (Boston Naming Test [BNT], Rey Auditory Verbal Learning Test [AVLT]) and CSF measures of Aβ42, Aβ40, and Aβ38. Mediation models explored relationships between TBI history and BNT scores with Aβ peptides as mediators. Results:The TBI group had higher CSF Aβ40 (t = –2.43, p = 0.017) and Aβ38 (t = –2.10, p = 0.038) levels than the CTRL group, but groups did not differ in CSF Aβ42 levels or Aβ42/Aβ40 ratios (p > 0.05). Both Aβ peptides negatively correlated with BNT (Aβ40: rho = –0.20, p = 0.032; Aβ38: rho = –0.19, p = 0.048) but not AVLT (p > 0.05). Aβ40 had a significant indirect effect on the relationship between TBI and BNT performance (β= –0.16, 95% CI [–0.393, –0.004], PM = 0.54). Conclusions:TBI may increase AD risk and cognitive vulnerability through Aβ overproduction. Biomarker models incorporating multiple Aβ peptides may help identify AD risk among those with TBI.
