Rationale and design of the NEwTON study: A prospective cohort study of patients at risk of chronic traumatic encephalopathy

Abstract

AbstractBackgroundTraumatic brain injury increases the risk of neurodegenerative diseases later in life. Repetitive head injury, more specific in contact sports, is associated with cognitive, neurobehavioral and motor impairments in the light of a unique neurodegenerative disorder: chronic traumatic encephalopathy (CTE). Yet, the clinical presentation, risk factors and diagnostic biomarkers of CTE have remained unclear. The general objective of the NEwTON study is to establish a prospective cohort of patients with high risk of CTE, to further study the link between repetitive head injury and neurodegeneration. We aim to phenotype the study population, identify potential biomarkers and measure clinical progression.MethodNEwTON is a prospective cohort study which aims to recruit approximately 80 patients at risk of CTE (features of the traumatic encephalopathy syndrome, Montenigro 2014) and healthy control subjects. Inclusion criteria are: history of repetitive head injury (contact sports, military service, other exposure), progressive cognitive and/or neurobehavioral symptoms, age 45‐75 years and symptom duration of ≥12 months. The control group will consist of age‐matched healthy participants without history of significant traumatic brain injury or participation in contact sports/professional military service. Subjects are invited to participate after diagnostic screening at our memory clinic or recruited by advertisement.ResultPatients will undergo comprehensive baseline screening, including neurological examination, neuropsychological tests, questionnaires and brain magnetic resonance imaging (MRI) for anatomical imaging, diffusion tensor imaging (DTI), resting state functional MRI (rsfMRI) and Quantitative Susceptibility Mapping (QSM). Questionnaires include topics on life‐time head injury, subjective cognitive change and neuropsychiatric symptoms. Blood and cerebrospinal fluid will be stored in the NEwTON biobank. Patients will be informed about our brain donation program in collaboration with the Netherlands Brain Brank. Testing for control subjects will be limited to baseline neuropsychological tests, blood draw and MRI. Patient follow‐up will take place annually and includes neuropsychological assessment, questionnaires and blood draw.ConclusionThe NEwTON study will contain the first cohort in the Netherlands with prospective observational data of patients with high risk of CTE. This study design will be an umbrella protocol and it is expected that other sub‐studies will use this cohort in the future.