Traumatic brain injury with loss of consciousness is associated with amyloid-beta burden and cerebral infarcts in community-dwelling older adults.

Abstract

A history of traumatic brain injury (TBI) with or without loss of consciousness (LOC) has been often considered a risk factor for dementia, and particularly for Alzheimer's disease (AD) dementia. However, the specific associations of TBI with AD, non-AD neurodegenerative, and vascular pathologies remain uncertain. We leveraged the Rush community-based longitudinal cohorts to examine these associations. The analytic sample included 1689 decedents (mean age-at-death= 89 years, SD=6.73; 32% male) from Rush longitudinal cohort studies of aging (the Memory and Aging Project, the Religious Order Study, and the Minority Aging Research Study). At autopsy, neuropathologic examination was performed to identify amyloid-beta, PHF-tangles, Parkinson's disease (PD) pathology, Lewy bodies, LATE-NC, hippocampal sclerosis, macroscopic infarcts, and microinfarcts. Multiple regression and logistic regression models were used to determine whether TBI with or without LOC (compared to no TBI exposure as reference group) were associated with AD and non-AD related neuropathologies after adjusting for age-at-death, sex, education, and in subsequent models APOEε4. Five hundred four (30.8%) individuals had TBI without LOC while 161 (9.5%) had TBI with LOC. TBI with LOC, but not without LOC was associated with amyloid-beta load (estimate= 0.25, SE= 0.09, p= 0.008). TBI with LOC was associated with higher odds of having one or more macroscopic (OR=1.45, 95% CI= 1.04, 2.02, p=0.025) and microscopic infarcts (OR=1.70, CI=1.21, 2.38, p=0.002). We found no association between TBI with or without LOC and PHF-tangles, LATE-NC, hippocampal sclerosis, PD pathology, or Lewy bodies. These results persisted after accounting for APOEε4. TBI in older adults is common. These data support the hypothesis that TBI, particularly with LOC is associated with amyloid-beta burden and cerebral infarcts. Further research should examine clinical correlates and specific mechanistic factors linking TBI to neurodegenerative and vascular pathologies.