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Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease marked by widespread accumulation of hyperphosphorylated tau (ptau). CTE is associated with a constellation of symptoms, including impairments in cognition, behavior, and mood. Although initially described in boxers as dementia pugilistrca, CTE has been diagnosed in athletes from a variety of backgrounds, as well as military veterans and other individuals exposed to traumatic brain injury (TBI). To date, the only shared risk factor for CTE is a history of single or multiple TBI. This work aimed to better elucidate the relationship between exposure to head impacts and the development and progression of CTE. Although the link between brain injury and CTE has been well described, the magnitude of this relationship has never been studied epidemiologically. The minimum prevalence of CTE was determined in a cohort at high risk of exposure to head impacts, specifically National Football League (NFL) athletes. All former NFL athletes who passed away in 2011 were identified; a subset of these athletes were studied and diagnosed with CTE to establish a minimum prevalence of CTE. The characteristics of those examined and diagnosed with CTE and those undiagnosed were explored. These analyses represent the first epidemiologic study of CTE; the high prevalence highlights the relationship between exposure to head impacts and the diagnosis of CTE. Next, the relationship between the nature of athletic exposure and CTE was quantified. An athletic history questionnaire was developed and integrated into a mathematical model, incorporating data from sensors placed in football players' helmets, to identify the theoretical frequency and magnitude of an athlete's head impact exposure. This model was adapted for use postmortem, and it was found that the duration of athletic exposure, total theoretical collisions experienced; and the sum of the 95th percentiles of the rotational acceleration endured, were all significantly associated with extent of CTE pathology. The relationships between the type of athletic exposure and the clinical presentation of disease and the specific neuroanatomic distribution of p-tau were also explored. These findings indicate the significant role of athletic exposure to head impacts on the diagnosis and progression of CTE, clinically and pathologically.

Increasing evidence indicates that the sooner treatment begins for patients with Alzheimer's Disease (AD), the better the chance of delaying progression of the disease. As a result, studies have begun focusing on risk factors for AD with the goal of identifying individuals with AD at the earliest possible stage. Such studies have found that individuals with Mild Cognitive Impairment (MCI) are at increased risk for AD and other forms of dementia. This study examines the potential mediating effect of a set of prospective risk factors, smoking and ApolipoproteinE (ApoE) genotype, on the incidence of MCI and AD. Although results of this study provide some preliminary evidence of an interaction, the study models presented here fail to reach significance. Additional studies are needed to confirm the hypothesis of an ApoE mediated relationship of smoking on MCI and AD.