Association between head trauma, amyloid and neurodegeneration in a population-based study of cognitively normal and mild cognitive impairment participants

Abstract

Head trauma has been associated with an increased risk of dementia and Alzheimer's disease (AD). Animal and post-mortem studies suggest that head trauma increases amyloid production and plaque deposition, but in vivo assessments are limited. We examined whether head trauma was associated with greater amyloid deposition and/or neurodegeneration among individuals who were cognitively normal (CN) or had Mild Cognitive Impairment (MCI). A population-based sub-sample of 589 individuals (448 CN and 141 MCI), aged 72–95, from the Mayo Clinic Study of Aging underwent PIB-PET, FDG-PET, and MR imaging. A history of head trauma was defined as a self-reported brain injury with at least momentary loss of consciousness or memory. We used Wilcoxon rank sum tests and chi-square tests to assess differences between subjects with and without a self-reported head trauma by cognitive status. Among the 448 CN individuals, 74 (16.5%) had a self-reported head trauma. There were no differences in PiB-PET, FDG-PET, or MR measures between CN subjects with and without head trauma. Of the 141 MCI cases, 25 (17.7%) self-reported a head trauma. Compared to those MCI without a head trauma, those with a head trauma had higher median PiB level (SUVR 2.2 vs. 1.6, p = 0.003). There was also a trend for lower hippocampal volumes (-0.95 vs. -0.72, p = 0.10), adjusted for head size. When stratified by APOE E4 genotype, the relationships were stronger among non-E4 carriers. However, we only had 9 MCI cases with a history of head trauma and an E4 allele. Results suggest that a history of self-reported head trauma is associated with higher levels of amyloid deposition in individuals with MCI, but not among CN individuals. These data raise interesting questions about the linkages between head trauma, amyloid, and cognitive impairment, although recall and other biases must be considered.