A Study of the Relationship Between Uric Acid and Substantia Nigra Brain Connectivity in Patients With REM Sleep Behavior Disorder and Parkinson's Disease

Abstract

Low levels of the natural antioxidant uric acid (UA) and the presence of REM sleep behavior disorder (RBD) are both associated with an increased likelihood of developing Parkinson's disease (PD). RBD and PD are also accompanied by basal ganglia dysfunction including decreased nigrostriatal and nigrocortical resting state functional connectivity. Despite these independent findings, the relationship between UA and substantia nigra (SN) functional connectivity remains unknown. In the present study, voxelwise analysis of covariance was used in a cross-sectional design to explore the relationship between UA and whole-brain SN functional connectivity using the eyes-open resting state fMRI method in controls without RBD, patients with idiopathic RBD, and PD patients with and without RBD. The results showed that controls exhibited a positive relationship between UA and SN functional connectivity with left lingual gyrus. The positive relationship was reduced in patients with RBD and PD with RBD, and the relationship was found to be negative in PD patients. These results are the first to show differential relationships between UA and SN functional connectivity among controls, prodromal, and diagnosed PD patients in a ventral occipital region previously documented to be metabolically and structurally altered in RBD and PD. More investigation, including replication in longitudinal designs with larger samples, is needed to understand the pathophysiological significance of these changes.

Why Does Hyperuricemia Not Necessarily Induce Gout?

“…SUA concentrations can be reflected by the intake from diet, in vivo purine metabolism, renal secretion, and intestinal degeneration [ 17 ]. In vivo, it may offer a neuroprotective advantage in the neurodegenerative Alzheimer’s disease [ 18 ], schizophrenia [ 19 ], Parkinson’s disease [ 20 ], multiple sclerosis [ 21 ], and serves as a depression biomarker [ 22 ]. SUA concentrations are linked to muscle strength and lean mass [ 23 ], although this was not shown in gastrointestinal tract cancer patients [ 24 ].…”

Extra‐striatal dopamine in Parkinson's disease with rapid eye movement sleep behavior disorder

“…However, for PD patients without RBD, the relationship was negative. (Ellmore et al, 2020). As the literature shows, PD patients with RBD possess a wide range of alterations relative to PD patients that go beyond the brainstem.…”

Signed Distance Correlation (SiDCo): A network analysis application of distance correlation for identifying metabolic networks disrupted in Dementia with Lewy Bodies

“…The Purine degradation pathway is induced by fructose through its rapid depletion of cellular ATP levels and activation of AMP deaminase (AMPD), eventually leading to the production of uric acid. Changes in the level of uric acid has been previously linked to the risk of dementia, with low levels associated with Parkinson's disease 34,31 and high levels of serum uric acid linked to vascular or mixed dementia and to a lesser extent AD 39 . Distance correlation analysis shows major differences in correlation partners for fructose with significant correlation with several other metabolites that are part of purine metabolism including ADP in addition to adenine, inosine and urea.…”