Objective: To determine the relationship between uric acid (UA) levels and functional connectivity in REM sleep behavior disorder (RBD) compared to controls.

Background: UA levels are lower in PD patients, with further decreases as the disease progresses1 . One hypothesis is that lower UA is a risk factor for neurodegeneration. Another risk factor is the sleep parasomnia RBD, which is accompanied by reduced substantia nigra (SN) functional connectivity2. Understanding whether the relationship between UA levels and resting state connectivity in subjects with RBD differs from controls could help clarify the predictive value of these two measures as longitudinal biomarkers.

Methods: Whole brain resting state fMRI (TR 2 secs), T1-weighted MRIs, and serum UA were collected from 45 RBD subjects and 27 matched controls. AFNI’s afni_proc.py routine was used to analyze fMRI with motion censoring and regression of confounding signals from ventricles and white matter. Group statistical analysis with AFNI’s 3dGroupInCorr was performed using an average seed time series built from a probabilistic mask of left and right SN

Results: Although mean UA was not significantly different from controls, RBD patients exhibited an altered relationship (p<0.05, cluster extent > 65 voxels) between UA levels and SN functional connectivity with left thalamus, right putamen, and lentiform nucleus. While controls showed a positive relationship between SN functional connectivity and UA levels in these areas, RBD subjects exhibited a negative relationship in which higher UA was accompanied by lower functional connectivity. (Figure 1)

Conclusions: We found preliminary evidence for a difference in the direction of correlation between SN functional connectivity and UA levels in RBD subjects compared to controls. Investigation of changing relationships across time between these two metrics in the same subjects is needed to determine their predictive value as longitudinal biomarkers of neurodegeneration.

References: 1. Wen M, Zhou B, Chen Y-H, Ma Z-L, Gou Y, Zhang C-L, et al. (2017) Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis. PLoS ONE12(3): e0173731. 2. Ellmore, T.M., Castriotta, R.J., Hendley, K.L., Aalbers, B.M., Furr-Stimming, E., Hood, A.J., Suescun, J., Beurlot, M.R., Hendley, R.T., Schiess, M.C. (2013) Altered nigrostriatal and nigrocortical functional connectivity in REM sleep behavior disorder. SLEEP, 36(12):1885-92.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/preliminary-evidence-for-an-altered-relationship-between-uric-acid-levels-and-resting-state-functional-connectivity-in-rem-sleep-behavior-disorder/