Association of traumatic brain injury with late life neuropathological outcomes in a community‐based cohort: Public health: Innovative methods in ADRD research. (7th December 2020)

• Record Type: Journal Article
• Authors: Gibbons, Laura E; Power, Melinda C; Walker, Rod L; Kumar, Raj G; Murphy, Alia; Latimer, Caitlin S; Melief, Erica J; Beller, Allison E; Keene, C Dirk; Larson, Eric B; Crane, Paul K; Dams‐O'Connor, Kristen
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 10
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.041939
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Despite extensive interest in risk for dementia following traumatic brain injury (TBI), there is scant research on neuropathological outcomes among community‐dwelling elders with TBI exposure. We previously reported an association of TBI resulting in loss of consciousness (LOC) with microinfarcts and Lewy body pathology, but TBI exposure data were limited to a single self‐report question. With expanded ascertainment data from medical records and structured interview on lifetime TBI exposure, we conducted a comprehensive investigation of neuropathological associations of TBI in a large autopsy cohort. Method: 780 older adults from the Adult Changes in Thought (ACT) study underwent brain autopsy (Table 1). Participants were members of Kaiser Permanente Washington who completed biennial clinic visits including self‐reported head trauma with LOC exposure. These data were supplemented with medical record abstraction, and, for 244 people, with structured interviews, increasing the sensitivity for TBI‐LOC in that sample from 16% to 20% (see Figure 1). Neuropathology outcomes included neurofibrillary tangle distribution (Braak), neuritic plaque density, Lewy body distribution, vascular pathology, hippocampal sclerosis, and cerebral cortical atrophy. Exposures of interest included TBI with or without LOC. We used Poisson regressions with robust standard errors adjusted for age, sex, education, and APO ε4 genotype, weighted back to the full cohort (n=5546; Table 2) in a bootstrapping procedure accounting for errors in estimating weights. Result: TBI with LOC was associated with increased cortical atrophy (Table 3). In those with the structured interview (including TBI without LOC), the neuropathological associations of TBI were attenuated; no outcomes were statistically significant (Table 4). These findings apply to the full ACT cohort, not just people with TBI data in the autopsy sample. Conclusion: Cerebral cortical atrophy results from chronic brain parenchymal injury, potentially including vascular brain injury and tauopathy. Understanding mechanisms underlying associations of TBI with microvascular brain injury and pathological tau are poorly understood; future studies deploying new techniques to better quantify these lesions and differentiate between TBI‐related, age‐related, and ADRD‐related pathways are needed.