Chapter 12 - Traumatic Brain Injury

Abstract

Head injury was identified as a putative risk factor for AD in case-control studies conducted in the early 1980s. Subsequent studies confirmed this association and revealed that injuries closer in time to dementia onset had much stronger associations with AD than injuries that occurred decades earlier. Pooled analysis of case-control studies showed that traumatic brain injury (TBI) is associated with AD with an OR of 2.20 (95% CI =1.14–4.22). An important finding of this analysis was that TBI is a risk factor for AD only in men, but not in women. Later studies, including an autopsy study, support this sex-specific association. Additionally it has been found that cases of AD with TBIs occur at a younger age than those without TBIs. Prospective cohort studies, in contrast to case-control studies, have mostly not shown associations between TBIs and AD. This may be due to nondemented participants who will soon become demented forgetting to report head injuries. In two historical cohort studies that used military records to document TBIs in young adulthood, strong associations with AD were demonstrated. Because of methodological shortcomings in the prospective cohort studies, the case-control and historical cohort studies provide more valid data and show that head trauma is likely an important risk factor for AD. Triggering of an AD neuropathological cascade by TBI has been found in about 30% of autopsied TBI cases, with APOE-ε4 carriers overrepresented in this group. Inflammation appears to be a common mediating mechanism in TBI-associated AD. Chronic traumatic encephalopathy, which has been attributed to repetitive head trauma experiences by athletes in contact sports, appears to be a separate neuropathologic process, but can coexist with AD.