Association of Traumatic Brain Injury with Late Life Neuropathological Outcomes in a Community-Based Cohort

Article type: Research Article

Authors: Gibbons, Laura E.^a | Power, Melinda C.^b | Walker, Rod L.^c | Kumar, Raj G.^d | Murphy, Alia^b | Latimer, Caitlin S.^e | Nolan, Amber L.^e | Melief, Erica J.^e | Beller, Allison^e | Bogdani, Marika^e | Keene, C. Dirk^e | Larson, Eric B.^a | Crane, Paul K.^a | Dams-O’Connor, Kristen^{d; *}

Affiliations: [a] General Internal Medicine, School of Medicine, University of Washington, Seattle, WA, USA | [b] George Washington University Milken Institute School of Public Health, Washington, DC, USA | [c] Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA | [d] Department of Rehabilitation and Human Performance, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [e] Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, USA

Correspondence: [*] Correspondence to: Kristen Dams-O’Connor, PhD, Icahn School of Medicine at Mount Sinai, Department of Rehabilitation and Human Performance, Department of Neurology, Brain Injury Research Center, One Gustave Levy Place, Box 1163, New York, NY 10029, USA. Tel.: +1 212 241 2221; E-mail: kristen.dams-o’[email protected].

Abstract: Background:Prior studies into the association of head trauma with neuropathology have been limited by incomplete lifetime neurotrauma exposure characterization. Objective:To investigate the neuropathological sequelae of traumatic brain injury (TBI) in an autopsy sample using three sources of TBI ascertainment, weighting findings to reflect associations in the larger, community-based cohort. Methods:Self-reported head trauma with loss of consciousness (LOC) exposure was collected in biennial clinic visits from 780 older adults from the Adult Changes in Thought study who later died and donated their brain for research. Self-report data were supplemented with medical record abstraction, and, for 244 people, structured interviews on lifetime head trauma. Neuropathology outcomes included Braak stage, CERAD neuritic plaque density, Lewy body distribution, vascular pathology, hippocampal sclerosis, and cerebral/cortical atrophy. Exposures were TBI with or without LOC. Modified Poisson regressions adjusting for age, sex, education, and APOE ɛ4 genotype were weighted back to the full cohort of 5,546 participants. Results:TBI with LOC was associated with the presence of cerebral cortical atrophy (Relative Risk 1.22, 95% CI 1.02, 1.42). None of the other outcomes was associated with TBI with or without LOC. Conclusion:TBI with LOC was associated with increased risk of cerebral cortical atrophy. Despite our enhanced TBI ascertainment, we found no association with the Alzheimer’s disease-related neuropathologic outcomes among people who survived to at least age 65 without dementia. This suggests the pathophysiological processes underlying post-traumatic neurodegeneration are distinct from the hallmark pathologies of Alzheimer’s disease.

Keywords: Alzheimer’s disease, atrophy, dementia, neuropathology, traumatic brain injury

DOI: 10.3233/JAD-221224

Journal: Journal of Alzheimer's Disease, vol. 93, no. 3, pp. 949-961, 2023