Abstract
Background
Falls represent one of the main complications of Parkinson’s disease (PD), significantly lowering quality of life. Cardiovascular autonomic neuropathy (cAN) is one of the key contributing factors to PD-associated falls. However, a direct quantification of its impact on the risk of falling in PD is still lacking. In this 12-month prospective study, we sought to evaluate the association between cAN and falls.
Methods
Fifty consecutive patients were evaluated with a standardized battery of autonomic testing, Unified Parkinson’s Disease Rating Scale, push and release (P&R) test, timed up and go test, freezing of gait (FOG) questionnaire, Montreal cognitive assessment (MoCA). Dyskinesia severity and presence of REM sleep behavioral disorder (RBD) were additionally considered. Patients were followed-up for 12 months.
Results
We observed a 38% prevalence of cAN. At baseline, 36% of patients reported at least one fall in the previous 6 months. This figure increased to 56% over the follow-up. After adjusting for age, disease duration, axial symptoms, MoCA and dopaminergic treatment, cAN was significantly associated with a 15-fold (OR 15.194) higher probability of falls; orthostatic hypotension (OH), the most common expression of cAN, with a 10-fold probability (OR 10.702). In addition P&R test (OR 14.021), RBD (OR 5.470) and FOG (OR 1.450) were independently associated with greater probability of falls.
Conclusions
cAN, including but not limited to OH, is a strong independent predictor of falls in PD. Future research endeavors clarifying to what extent pharmacological and non-pharmacological treatments targeting autonomic dysfunctions might reduce the risk of falls are warranted.
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AR: conception and design of the study; acquisition, analysis and interpretation of data; writing of the first draft and review and critique of the manuscript. MZ: conception and design of the study; analysis and interpretation of data; writing of the first draft and review and critique of the manuscript. AM: design of the study; analysis and interpretation of data; review and critique of the manuscript. DC: design of the study; analysis and interpretation of data; review and critique of the manuscript. MS: design of the study; acquisition and interpretation of data; review and critique of the manuscript. EM: design of the study; acquisition and interpretation of data; review and critique of the manuscript. ACA: design of the study; acquisition and interpretation of data; review and critique of the manuscript. FV: design of the study; acquisition and interpretation of data; review and critique of the manuscript. SM: design of the study; analysis and interpretation of data; review and critique of the manuscript. LL: conception and design of the study; analysis and interpretation of data; review and critique of the manuscript. All the co-authors listed above gave their final approval of this manuscript version.
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Dr Romagnolo has received grant support and speaker honoraria from AbbVie, speaker honoraria from Chiesi Farmaceutici and travel grants from Medtronic, Lusofarmaco and UCB Pharma. Dr Zibetti has received speaker’s honoraria from Medtronic, Chiesi Farmaceutici, UCB Pharma, and AbbVie. Dr Merola is supported by NIH (KL2 TR001426) and has received speaker honoraria from CSL Behring, Abbvie, and Cynapsus Therapeutics. He has received grant support from Lundbeck. Dr Canova reports no disclosures. Dr Sarchioto reports no disclosures Dr Montanaro reports no disclosures. Dr Artusi reports no disclosures. Dr Vallelonga reports no disclosures. Dr Maule reports no disclosures. Dr Lopiano has received honoraria for lecturing and travel grants from Medtronic, UCB Pharma and AbbVie.
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A. Romagnolo had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Ethical standard
The authors declare that they acted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The local institutional review board (Comitato Etico Interaziendale Città della Salute e della Scienza di Torino; Protocol n° 0050175/CEI-715) approved the study and all participants provided written informed consent.
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Dr Romagnolo and Dr Zibetti contributed equally to this manuscript
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Romagnolo, A., Zibetti, M., Merola, A. et al. Cardiovascular autonomic neuropathy and falls in Parkinson disease: a prospective cohort study. J Neurol 266, 85–91 (2019). https://doi.org/10.1007/s00415-018-9104-4
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DOI: https://doi.org/10.1007/s00415-018-9104-4