Background:
Repeated concussions in retired rugby union players may increase the risk of cognitive decline [1]. Previously, we have demonstrated that professional rugby union players are characterised by a suppression in the systemic bioavailability of nitric oxide (NO) [1], an established risk factor for Alzheimer’s disease that serves as a major cause of disability and dependency in older adults [2]. Evidence suggests that adequate dietary intake, notably folate, protects against cognitive decline and dementia [3] and this may be mediated through a free radical-mediated pathway involving NO. The present study examined if low folate intake and corresponding reduction in systemic NO bioavailability and cerebral perfusion would be associated with mild cognitive impairment in retired rugby union players.
Methods:
Twenty retired rugby union players aged 64 ± 5 years having sustained 3 concussions incurred over 22 years were compared to 21 sex, age-, cardiorespiratory fitness- and education-matched controls with no prior participation in contact sports or concussion history. Fasted venous blood was obtained for the assessment of plasma bioactive NO (reductive ozone-based chemiluminescence), determined as the cumulative concentration of nitrite (NO) and S-nitrosothiols (RSNO). The Montreal Cognitive Assessment (MoCA) was employed to assess cognition and a self-administered validated semi-quantitative food frequency questionnaire (FFQ) was used to estimate typical food intake over the past 12 months. Dietary data were converted into estimated nutrient intakes using a nutritional software package (Q-Builder, Tinuviel Software; Anglesey, UK). Middle cerebral artery blood flow velocity (MCAv) was determined using transcranial doppler ultrasound. Following confirmation of distribution normality (Shapiro Wilks W tests), between-group differences were assessed using independent samples t-tests. Data are expressed as mean ± standard deviation (SD) and significance established at P <0.05.
Results:
Compared to controls, players were characterised by a lower intake of folate (327 ± 81 µg vs. 415 ± 103 µg, P = 0.004), lower basal bioactive NO (71 ± 44 nM/L vs. 86 ± 35 nM/L, P = 0.049), lower MCAv (45 ± 9 cm/s vs. 51 ± 7 cm/s, P = 0.004) and lower MoCA scores (24 ± 3 points vs. 26 ± 2 points, P = 0.020), with the latter clinically defined as mild cognitive impairment (MCI).
Conclusions:
No studies have previously investigated nutrient intake and the integrated mechanistic link to cognitive decline in retired rugby union players with an established concussion history. Collectively, these findings demonstrate that retired players are characterized by inadequate folate intake, reduced NO bioavailability and lower cerebral perfusion that likely precede MCI. Folate plays a key role in reducing serum homocysteine concentration, the latter a modifiable risk factor for cognitive decline and dementia [3, 4]. Similarly, folate has been shown to improve vascular NO bioavailability subsequent to a reduction in systemic oxidative-nitrosative stress [5] which may in turn improve both perfusion and cognition [2]. Folate supplementation may confer neuro-prophylactic benefits in retired players with concussion history and attenuate their trajectory towards accelerated brain ageing.