NEurodegeneration: Traumatic brain injury as Origin of the Neuropathology

Traumatic brain injury is associated with a higher risk for neurodegenerative
disorders later in life. Specifically, repetitive head injury is the cause of
the neurodegenerative disorder: chronic traumatic encephalopathy (CTE), which
is characterized by accumulation of hyperphosphorylated tau (p-tau), found
perivascular at the depths of the sulci in the cerebral cortex. The clinical
manifestation of CTE is highly variable, with a range of impairments in
cognition, behavior and mood, but no definite consensus about clinical
diagnostic criteria for CTE has been reached yet, in order to diagnose CTE
during life. Furthermore, the role of (neuro-imaging) biomarkers in CTE
diagnostics remain unclear.

The primary goal of NEwTON is to study the link between repetitive head injury
and neurodegeneration, leading to cognitive, psychiatric and behavioral
symptoms as found in CTE. We will collect a prospective cohort of patients at
high risk of CTE, with symptoms related to traumatic encephalopathy syndrome
(TES) with a history of repetitive head injury and compare this group to
matched controlled subjects.
We aim to extensively phenotype the study population, identify the clinical
progression, identify potential biomarkers in cerebrospinal fluid (CSF),
determine neuro-imaging features.

The NEwTON study is a single center prospective obervational cohort study

The first baseline tests take an average of 6-8 hours for patients from
external, 2,5-4 hours for patients who has already visited the memory clinic
previously and 2,5 hours for controls subjects, with another two follow-up
visits of approximately 2,5 hours for patients. Follow-up tests will include
neuropsychological testing and questionnaires. The testing is organized in
similar way as in regular memory clinic care. There is no direct benefit for
participants, but they will highly contribute to research into CTE
Neuropsychological testing and questionnaires might be considered tiresome, but
this depends on the mental resilience of the participant.

CSF collection by a lumbar puncture is also a common procedure in neurology
practice (only for patients form external) and we gained a lot of experience in
the memory clinic, where all patients undergo a lumbar puncture. A lumbar
puncture can cause post-punctional headache in less than 5% of the cases. which
is basically self-limiting, however in a few percentage of the cases, a blood
patch is needed.
An MRI scan is widely used medical practice. The narrow space and the loud
noise can cause some discomfort, but the risk of MRI scans are negligible (when
contra-indications are asked well)

Concluding, because of the minimal to negligible risks and the valuable nature
of this project (this will be the research first project to CTE in the
Netherlands), we consider this burden to be acceptable for participants.