Positive Association of Ascorbate and Inverse Association of Urate with Cognitive Function in People with Parkinson’s Disease

Abstract

Oxidative stress is thought to contribute to the aetiology of neurological disorders such as Parkinson’s disease. Ascorbate (vitamin C) is a potent antioxidant and is associated with neurological and cognitive function. In this study we assessed the ascorbate status of a cohort of people with Parkinson’s disease (n = 215), aged 50–90 years, compared with a cohort of age matched healthy controls (n = 48). The study sample’s cognitive status ranged from normal to mild cognitive impairment and dementia. There was no difference between the Parkinson’s disease and healthy control groups with respect to mean ascorbate status, however, a higher proportion of participants with Parkinson’s disease had hypovitaminosis C (i.e., <23 μmol/L) compared with healthy controls (20% vs. 8%, respectively). Within the Parkinson’s disease group, Montreal Cognitive Assessment (MoCA) scores correlated positively with ascorbate concentrations, with higher ascorbate status associated with better cognitive function (r = 0.14, p = 0.045). Participants with hypovitaminosis C had significantly lower MoCA scores relative to participants with ascorbate concentrations >23 µmol/L (p = 0.014). Ascorbate concentrations were significantly lower in the cognitively impaired subgroup compared with the normal cognition subgroup in the Parkinson’s disease cohort (p = 0.03). In contrast, urate showed an inverse correlation with cognitive function (r = −0.19, p = 0.007), with higher urate concentrations observed in the cognitively impaired subgroup compared with the normal cognition subgroup (p = 0.015). There was an inverse association between ascorbate status and urate concentrations (r = −0.15, p = 0.017). Plasma protein carbonyls, a measure of systemic oxidative stress, were not significantly different between the Parkinson’s disease cohort and healthy controls, and there was no association with cognitive function (r = 0.09, p = 0.19) or with ascorbate status (r = −0.05, p = 0.45). Overall, our study showed ascorbate status was positively associated with cognitive function in Parkinson’s disease, suggesting that longitudinal studies investigating the temporal sequence of cognitive decline and ascorbate status are warranted.

Vitamin C Inhibits Ubiquitination of Glutamate Transporter 1 (GLT-1) in Astrocytes by Downregulating HECTD1

“…A negative correlation between VC intake and PD progression, and a positive association with cognitive function in PD patients, have both been reported in the literature. , Most authors have suggested that the antioxidant function of VC is at the basis of these correlations. , Here, we present evidence that another pathway may be involved: the ubiquitination of GLT-1, which can be reduced by VC. Ubiquitination involves the addition of ubiquitin polypeptides to amino acids, mainly to lysines, in proteins through isopeptide bonds, which are then catalyzed by three enzymes, E1, E2, and E3.…”

“…A negative correlation between VC intake and PD progression, and a positive association with cognitive function in PD patients, have both been reported in the literature. 30,31 Most authors have suggested that the antioxidant function of VC is at the basis of these correlations. 32,33 Here, we present evidence that another pathway may be involved: the ubiquitination of GLT-1, which can be reduced by VC.…”

Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

“…Ascorbate also functions in the regeneration of Vitamin E, another antioxidant, by reducing the tocopheroxyl radical [90]. A recent study demonstrated a higher proportion of hypovitaminosis C in PD patients compared to healthy controls, and that this deficiency of ascorbate was associated with worse cognitive impairment and lower MoCA scores [91]. PD patients have significantly lower serum ascorbate [92], and furthermore, reduced lymphocyte ascorbate concentration is associated with increased PD severity, as assessed by Hoehn-Yahr staging [93].…”