Traumatic brain injury and late-life dementia.Handb Clin Neurol 2015; 128:711-22HC
Little is known of the impact of traumatic brain injury (TBI) on outcomes decades later when the effects of the injury interact with the aging brain. Some, but not all, epidemiologic studies have reported an association between TBI and increased risk of Alzheimer's disease (AD) and other neurodegenerative disorders years after the injury. There is evidence that this association has a dose-response pattern such that risk of dementia progressively increases as the number and severity of head injuries increase. Some studies have shown that one of the mechanisms underlying the association is that TBI may contribute to earlier onset of dementia. The APOE ϵ4 allele has been proposed as a biological link between TBI and AD because individuals with an APOE ϵ4 allele show typical AD pathology within a short period postinjury and are at increased risk of poorer cognitive outcomes. There are also likely other, yet to be identified factors that interact with the postinjury damage and aging-related brain changes leading to exacerbated cognitive decline and dementia. Given the large number of young individuals with military, sports-related, and other causes of head injuries, there is a window of opportunity and an urgency to understand the link between TBI and dementia before these TBI survivors reach the age of risk for dementia.