Objective: To investigate the association between probable RBD (pRBD) and cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, in patients with Parkinson’s disease (PD).

Background: RBD in PD is caused by dysfunction in the subcoeruleus and magnocellularis nuclei of the brainstem. Isolated RBD is associated with ¹²³I-metaiodobenzylguanidine cardiac sympathetic nerve scintigraphy (MIBG) positivity, and MIBG positivity is associated with levels of CSF 5-HIAA in PD. However, the association between RBD and CSF 5-HIAA remains unclear.

Method: We retrospectively evaluated consecutive patients with PD (MDS 2015 criteria) who underwent CSF examination between 2021 and 2025. Patients who had antiparkinsonian drugs, serotonergic antidepressants, or a history of depression or heart failure were excluded. pRBD positivity was defined as RBDSQ-J ≥ 6. Clinical characteristics, MIBG delayed H/M ratios, and CSF 5-HIAA levels were compared between patients with and without pRBD. Multivariable linear regression analyses were performed using log-transformed CSF 5-HIAA as the dependent variable. Mediation analyses evaluated whether MIBG delayed H/M ratios mediated the association between pRBD and CSF 5-HIAA.

Results: Eighty-five patients with PD were included (pRBD-negative n = 70, pRBD-positive n = 15). Age, sex, disease duration, Hoehn–Yahr stage, intervals between lumbar puncture and DAT-SPECT or MIBG, orthostatic hypotension, and scores of MMSE and GDS did not differ between groups. Patients with pRBD showed significantly lower delayed MIBG H/M ratios compared with those without pRBD (p = 0.009). CSF 5-HIAA levels were significantly lower in the pRBD-positive group than in the pRBD-negative group (9.9 ± 3.3 vs 14.5 ± 6.9 ng/mL, p < 0.001). Multivariable regression analyses demonstrated that pRBD positivity was significantly associated with reduced log-transformed CSF 5-HIAA after adjustment for age, sex, and disease duration (β = -0.33, p = 0.01). The association was attenuated after inclusion of MIBG delayed H/M ratios. Mediation analysis showed that MIBG delayed H/M ratios partially mediated the association between pRBD and CSF 5-HIAA, accounting for approximately 29% of the total effect (p = 0.02).

Conclusion: pRBD in PD was associated with reduced CSF 5-HIAA levels. Cardiac sympathetic denervation assessed by MIBG scintigraphy may partially mediate this relationship.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-between-probable-rbd-and-reduced-csf-5-hydroxyindoleacetic-acid-levels-in-parkinsons-disease/