Objective: To explore the association between levels of α-synuclein burden and urinary dysfunction in early de novo (untreated) Parkinson’s disease (PD) patients.

Background: Urinary dysfunction is a common non-motor symptom of PD and the pathophysiology underlying its development is currently unknown. Deposition of α-synuclein inclusions has been associated with the dysfunction of pelvic visceral afferents and suggested as primum movens in the development of urinary dysfunction. However, the association between levels of α-synuclein burden and urinary dysfunction in PD has not yet been explored.

Methods: We extracted data and conducted analysis of cerebrospinal fluid(CSF) α-synuclein levels from the baseline data of Parkinson’s Progression Markers Initiative database in early de novo PD patients with confirmed striatal dopaminergic deficits assessed by [123I]FP-CIT SPECT molecular imaging. Subjective urinary dysfunction has been evaluated using MDS-UPDRS Part-I item 1.10 and correlated with CSF α-synuclein levels, [123I]FP-CIT striatal uptake and other clinical features.

Results: 205/398(51.5%) of early de novo PD patients showed presence of urinary dysfunction. Higher severity of urinary dysfunction was associated with higher α-synuclein CSF levels(Pearson’s correlation [r]=0.105, p=0.036), lower [123I]FP-CIT levels(Striatum: r=-0.112, p=0.025, Caudate: r=-0.107, p=0.033, Putamen: r=-0.105, p=0.036), and higher severity of motor(MDS-UPDRS part-III: r=0.163, p=0.001) and non-motor(MDS-UPDRS part-I: r=0.557, p<0.0001) symptoms. Higher severity of urinary dysfunction was also correlated with higher severity of postural instability(r=0.225, p<0.0001) and bradykinesia(r=0.120, p=0.017) but not with rigidity(r=0.061, p=0.222) or resting tremor(Amplitude:r=0.037, p=0.464; Constancy:r=0.014, p=0.788). By using a multivariate model including [123I]FP-CIT caudate and putamen uptake and MDS-UPDRS values, only α-synuclein CSF levels was correlated with urinary dysfunction (r=0.386, p=0.046).

Conclusions: Our data suggest that urinary dysfunction is associated with CSF levels of α-synuclein and may be considered a clinical surrogate of visceral α-synuclein deposition. Further studies aimed to measure urinary dysfunction objectively are needed to clarify this intrigues hypothesis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/synuclein-csf-levels-correlate-with-urinary-dysfunction-in-early-de-novo-parkinsons-disease-patients/