Probing the Link between Concussion and Neurodegenerative Diseases: Prodromal Diagnosis and Nutraceutical Interventions

Abstract

Concussions are a growing concern in contact sports due to their link with long-term neurodegenerative diseases such as Alzheimer’s, Amyotrophic Lateral Sclerosis (ALS), and Chronic Traumatic Encephalopathy (CTE). This thesis explored the diagnostic and therapeutic potential of biomarkers and novel interventions across both human and preclinical models. The UK Rugby Health study is the first of its kind to explore a large cohort of retired male professional rugby players, and their physical and mental health status in their retirement, compared to non-contact sportspersons. Serum biomarkers were analyzed in these retired UK rugby players with a history of >5 concussions (n=32) compared to non-contact sport controls (n=27). Elevated levels of t-tau, p-tau181, ApoE4, 27-HC, ceramides, total triglycerides, and increased exosome size, along with reduced RBP-4 and 24-HC, were observed in the highly repetitively concussed group, highlighting potential early prodromal indicators of neurodegeneration. This urgently needs a follow-up study to confirm or extend our knowledge, with a view to encourage interventions as early as possible. Effective and safe interventions are required to improve health and wellbeing and recovery in contact sport during and after careers. Drosophila melanogaster exposed to repetitive high-impact trauma showed reduced lifespan, impaired motor function, and increased oxidative stress. The novel phytoceutical supplement (CONKA1) comprises of Withania somnifera, Curcuma longa, Melissa officinalis, Rhodiola rosea, Vaccinium myrtillus) significantly improved healthy longevity, mobility, and oxidative stress resilience in the flies. In a study with contact sport athletes (rugby and football, male and female, n=65) over 4 weeks, CONKA1 supplementation revealed significant improvements in cognitive performance evaluated using the newly developed Integrated Cognitive Assessment (ICA) tool. Together, these studies suggest that repetitive concussion induces a range of detectable prodromal biomarker changes, useful for early diagnosis of functional deficits and neuropathologies, that may be targeted by phytoceutical interventions such as CONKA1, with potential in both prevention and recovery strategies for contact sport athletes.