Objective: To estimate the onset of postural instability in a cohort of Parkinson’s disease (PD) patients.

Background: The Cincinnati Cohort Biomarker Program (CCBP), launched in 2019, is a non-hypothesis-driven study aimed to unveil biomarkers of individualized biological mechanisms associated with neurodegeneration [1]. Although phenotype-agnostic, certain phenotypic measures, such as postural instability, are considered disease milestones and have not been studied prospectively in Parkinson’s disease [2,3].

Method: We examined all our PD patients from the cohort of 572 subjects (which also included patients with PD-like disoders; Alzheimer’s disease (AD) and AD-like disorders) up to February 28, 2022. All participants undergo yearly follow-up visits with full neurological assessments. Postural instability was defined as MDS-UPDRS item 3.12 score ≥ 3, or Hoehn & Yahr scale ≥ 3. If patients had postural instability at enrollment, we reviewed their charts to ascertain the date when postural instability was documented.

Results: The cohort included 355 PD patients (male, 62.3%; age, 67.8 ± 10.1 years [range 21–90]; disease duration, 8 ± 6.7 years [range, 0.1–37 years]). In 22 (6.2%) patients, the symptoms of PD started at the age of 40 years or younger, and in 3 (0.9%) patients, before age 21 years. One hundred fifteen (32.4%) patients have had at least their one-year follow-up visit after enrollment. Forty-five (12.7%) patients had postural instability at enrollment, and 5/107 patients (4.6%) developed postural instability after a mean follow-up of 14.1 ± 4.4 months. Postural instability was ascertained in 2.3%, 27.8% and 69.8% of patients at 1, 10 years and 20 years from symptoms onset.

Conclusion: The inclusive CCBP cohort provides naturalistic estimates of postural instability according to disease duration that may serve as anchors for future disease-modifying studies.

References: [1] Sturchio A, Marsili L, Vizcarra JA, Dwivedi AK, Kauffman MA, Duker AP, Lu P, Pauciulo MW, Wissel BD, Hill EJ, Stecher B, Keeling EG, Vagal AS, Wang L, Haslam DB, Robson MJ, Tanner CM, Hagey DW, El Andaloussi S, Ezzat K, Fleming RMT, Lu LJ, Little MA, Espay AJ. Phenotype-Agnostic Molecular Subtyping of Neurodegenerative Disorders: The Cincinnati Cohort Biomarker Program (CCBP). Front Aging Neurosci. 2020 Oct 8;12:553635. doi: 10.3389/fnagi.2020.553635. PMID: 33132895; PMCID: PMC7578373.
[2] Marsili L, Vizcarra JA, Sturchio A, Dwivedi AK, Keeling EG, Patel D, Mishra M, Farooqi A, Merola A, Fasano A, Mata IF, Kauffman MA, Espay AJ. When does postural instability appear in monogenic parkinsonisms? An individual-patient meta-analysis. J Neurol. 2021 Sep;268(9):3203-3211. doi: 10.1007/s00415-020-09892-3. Epub 2020 May 20. PMID: 32436106.
[3] Mahajan A, Marsili L, Dwivedi AK, Situ-Kcomt M, Grimberg MB, Wachter N, Abdelghany E, Duque KR, Espay AJ. Timing matters: Otological symptoms and Parkinson’s disease. Parkinsonism Relat Disord. 2021 Sep;90:23-26. doi: 10.1016/j.parkreldis.2021.07.030. Epub 2021 Jul 29. PMID: 34343875.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/postural-instability-in-parkinsons-disease-phenotypic-data-from-the-cincinnati-cohort-biomarker-program/