Blood Markers in Relation to a History of Traumatic Brain Injury Across Stages of Cognitive Impairment in a Diverse Cohort

Article type: Research Article

Authors: LoBue, Christian^{a; b; *} | Stopschinski, Barbara E.^{c; d} | Saez Calveras, Nil^{c; d} | Douglas, Peter M.^e | Huebinger, Ryan^f | Cullum, C. Munro^{a; b; c} | Hart, John^{a; c} | Gonzales, Mitzi M.^{g; h}

Affiliations: [a] Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA | [b] Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA | [c] Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA | [d] Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA | [e] Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA | [f] Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA | [g] Department of Neurology, Cedars Sinai Medical Center, Los Angeles, CA, USA | [h] Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, San Antonio, TX, USA

Correspondence: [*] Correspondence to: Christian LoBue, PhD, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. Tel.: +1 214 648 4646; Fax: +1 214 648 4660; E-mail: christian.lobue@utsouthwestern.edu.

Abstract: Background:Traumatic brain injury (TBI) has been linked to multiple pathophysiological processes that could increase risk for Alzheimer’s disease and related dementias (ADRD). However, the impact of prior TBI on blood biomarkers for ADRD remains unknown. Objective:Using cross-sectional data, we assessed whether a history of TBI influences serum biomarkers in a diverse cohort (approximately 50% Hispanic) with normal cognition, mild cognitive impairment, or dementia. Methods:Levels of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (T-tau), and ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) were measured for participants across the cognitive spectrum. Participants were categorized based on presence and absence of a history of TBI with loss of consciousness, and study samples were derived through case-control matching. Multivariable general linear models compared concentrations of biomarkers in relation to a history of TBI and smoothing splines modelled biomarkers non-linearly in the cognitively impaired groups as a function of time since symptom onset. Results:Each biomarker was higher across stages of cognitive impairment, characterized by clinical diagnosis and Mini-Mental State Examination performance, but these associations were not influenced by a history of TBI. However, modelling biomarkers in relation to duration of cognitive symptoms for ADRD showed differences by history of TBI, with only GFAP and UCHL1 being elevated. Conclusions:Serum GFAP, NFL, T-tau, and UCHL1 were higher across stages of cognitive impairment in this diverse clinical cohort, regardless of TBI history, though longitudinal investigation of the timing, order, and trajectory of the biomarkers in relation to prior TBI is warranted.

Keywords: Alzheimer’s disease, brain injury, dementia, cognitive dysfunction, serum marker

DOI: 10.3233/JAD-231027

Journal: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 345-358, 2024