Traumatic brain injury fast-forwards Alzheimer's pathology: evidence from amyloid positron emission tomorgraphy imaging.

Abstract

Traumatic brain injury (TBI) has been proposed as a risk factor for Alzheimer's disease (AD), although the mechanisms underlying the putative association are poorly understood. We investigated elderly individuals with a remote history of TBI, aiming to understand how this may have influenced amyloidosis, neurodegeneration, and clinical expression along the AD continuum. Total of 241 individual datasets including amyloid beta (Aβ) positron emission tomography ([18F]-AV45), structural MRI, and neuropsychological measures, were obtained from the Alzheimer's Disease Neuroimaging Initiative. The data were stratified into groups with (TBI +) or without (TBI-) history of head injury, and by clinical dementia rating (CDR) scores, into subgroups with normal cognition (CDR = 0) and those with symptomatic cognitive decline (CDR ≥ 0.5). We contrasted the TBI + and TBI- subgroups with respect to the onset age and extent of cognitive decline, cortical thickness changes, and Aβ standard uptake value (SUVr). Compared to the TBI-/CDR ≥ 0.5 subgroup, the TBI + /CDR ≥ 0.5 subgroup showed a 3-4year earlier age of cognitive impairment onset (ACIO, p = 0.005). Among those participants on the AD continuum (Aβ + , as defined by a cortical SUVr ≥ 1.23), irrespective of current CDR, a TBI + history was associated with greater Aβ deposition and more pronounced cortical thinning. When matched for severity of cognitive status, the TBI + /CDR ≥ 0.5 group showed greater Aβ burden, but earlier ACIO as compared to the TBI-/CDR ≥ 0.5, suggesting a more indolent clinical AD progression in those with TBI history. Remote TBI history may alter the AD onset trajectory, with approximately 4years earlier ACIO, greater amyloid deposition, and cortical thinning.