The synergistic effect of concussions and aging in women? Disparities and perspectives on moving forward

Abstract

Sports-related concussion is a significant health concern affecting approximately 1.6-3.8 million people in the USA each year [1]. Although male athletes are exposed to more contact in sports [2], rates of concussion are higher for female athletes in sex-comparable sports at both the high school and collegiate level [2-4]. Furthermore, female athletes tend to report a greater number of symptoms and take longer to recover from concussion compared with male athletes [4-6]. Impaired cognitive function and alterations in brain structure and function have been noted in the acute phase after injury in both males and females, and it has been reviewed in depth recently [5,7,8]. However, the majority of research assessing the long-term implications of mild traumatic brain injury (TBI) or sports-related concussion has been limited to male athletes. Past studies have suggested that a history of TBI increases the risk of a number of neurodegenerative diseases, including Alzheimer's disease [9,10], Parkinson's disease [11], amyotrophic lateral sclerosis [12,13], frontotemporal dementia [14] and chronic traumatic encephalopathy (CTE) [15-17]. With the discovery of CTE in male athletes with a history of repetitive brain trauma [15-17], considerable focus has been placed on the link between sports-related concussions and the development of CTE. CTE, originally termed dementia pugilistica, was first discovered by Harrison Martland in boxers, whom he described as being punch drunk [18]. A further series of cases described by Corsellis and colleagues noted a similar pattern of histological and cerebral changes in boxers [19]. In 2005, Dr. Bennet Omalu discovered neuropathological changes characteristic of CTE in a retired professional football player, who died due to myocardial infarction [15]. A recent postmortem study found CTE in 177 of the 202 brains examined, all of whom were deceased subjects who participated in contact sport with repetitive exposure to brain trauma [20]. Furthermore, a retrospective autopsy series of individuals whose brains were donated to a neuropathology brain bank found that a third of individuals with a history of participation in contact sports showed evidence of CTE; no autopsies on individuals without a history of contact sports showed evidence of CTE [21]. It should be noted that recent work has also found CTE pathology in those without a history of repetitive brain trauma [22,23] CTE is characterized by the accumulation of hyperphosphorylated tau in the depths of sulci, that progresses from the frontal to temporal cortical regions [17]. A thorough discussion of CTE pathology can be found in the following references [16,17,20,24]. Although CTE cannot yet be diagnosed in the living, retrospective medical and mental health histories from family members of those diagnosed with CTE suggests that there is a characteristic cognitive and behavioral profile of impairments dependent upon when disease progression begins [25]. However, to date, no female athlete has been diagnosed with CTE, and furthermore, no prospective in vivo or neuropathological studies have assessed the overall long-term effects of concussions in female athletes. Thus, we cannot begin to assess