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Role of the UPSIT score in performing synucleinopathy diagnosis

D. Rebolledo Garcia, JC. Lopez Hernandez, JA. Romero Mera (New York, USA)

Meeting: 2025 International Congress

Keywords: Autonomic dysfunction, Autonomic nervous system, Parkinsonism

Category: Parkinsonism (Other)

Objective: Determine if the UPSIT score is used to diagnose alpha-synucleinopathies and whether it correlates with neurogenic orthostatic hypotension (nOH).

Background: Establishing a new diagnosis of synucleinopathy would be challenging. Together with RBD enactment behavior disorder, the UPSIT score has been used as a possible biomarker to predict prodromic synucleinopathies. However, the UPSIT score has no clear role in diagnosing synucleinopathies for the first time and whether it correlates with nOH.

Method: Between January 1, 2024, and January 1, 2025, patients were referred for nOH, suspected of having synucleinopathies such as Parkinson’s disease (PD), multiple system atrophy (MSA), and Lewy body dementia (LBD). They underwent autonomic testing and performed the UPSIT score.

Results: A total of n=34 patients participated in the study. The final diagnoses included PAF n=8 (23.5%), PD n=7 (20.6%), MSA n=8 (23.5%), and LBD n=11 (32.4%). Autonomic testing results indicated that n=22 (64.7%) patients had nOH, while n=29 (85.3%) experienced supine hypertension. Patients with PAF showed significant drops in systolic (p=0.003) and diastolic blood pressure (p=0.01) after 3 minutes of tilting; however, no significant difference was observed among all groups (p=0.15). There was no correlation between UPSIT scores and systolic (r²=0.007, p=0.95) and diastolic (r²=0.07, p=0.54) blood pressure at the 3-minute tilt, nor with the delta heart rate/systolic blood pressure ratio (HR/SBP ratio) at that same time point (r²=-0.05, p=0.68). The Valsalva maneuver revealed that late phase II was absent in n=34 (88.2%) of patients who scored lower on the UPSIT compared to those who exhibited normal late phase II (p=0.044). Correlation analysis showed a negative relationship between age and UPSIT score (r²=-0.25, p=0.042) and between age and the DHR/SBP ratio (r²=-0.36, p=0.004). Patients with PD and LBD had lower UPSIT scores than those with MSA (p=0.03). No statistically significant differences were found in UPSIT scores between PD and LBD patients (p=0.06). Finally, there was no correlation between UPSIT score thresholds and a PAF diagnosis (p=0.06).

Conclusion: The UPSIT score can be used to diagnose synucleinopathies. While the UPSIT score varied among patients with PAF, it distinguished between MSA and LBD/PD patients. Interestingly, there was a tendency for lower UPSIT scores to correlate with sympathetic failure (late phase II and phase IV absent and nOH).

Figure 1.0 MDS abstract 2.0

Figure 1.0 MDS abstract 2.0

Figure 2 MDS abstracy 2.0

Figure 2 MDS abstracy 2.0

References: 1. Millar Vernetti P, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Shibao CA, Peltier A, Freeman R, Gibbons C, Goldstein DS, Low PA, Singer W, Coon EA, Miglis MG, Wenning GK, Fanciulli A, Vernino S, Betensky RA, Kaufmann H. Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study. Brain. 2024 Jul 5;147(7):2440-2448. doi: 10.1093/brain/awae033.
2. Coon EA, Mandrekar JN, Berini SE, Benarroch EE, Sandroni P, Low PA, Singer W. Predicting phenoconversion in pure autonomic failure. Neurology. 2020 Aug 18;95(7):e889-e897. doi: 10.1212/WNL.0000000000010002.

To cite this abstract in AMA style:

D. Rebolledo Garcia, JC. Lopez Hernandez, JA. Romero Mera. Role of the UPSIT score in performing synucleinopathy diagnosis [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/role-of-the-upsit-score-in-performing-synucleinopathy-diagnosis/. Accessed October 5, 2025.
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