Systematic Review of Cardiovascular Autonomic Dysfunction in Alpha-Synucleinopathies

Abstract Background Alpha-synucleinopathies encompass a range of neurodegenerative disorders defined by development of abnormal alpha-synuclein pathology throughout the nervous system, including Parkinson’s Disease, Lewy Body Disease, Multiple Systems Atrophy and Primary Autonomic Failure. Autonomic dysfunction is a prominent feature of alpha-synucleinopathies, with cardiovascular dysautonomia being the second most common autonomic complication. These conditions exhibit a prodromal phase with early autonomic dysfunction, but the role of autonomic biomarkers in disease prognosis and phenoconversion remains unclear. Methods This systematic review addresses whether cardiovascular autonomic dysfunction, particularly orthostatic hemodynamics, predicts prognosis and phenoconversion in alpha-synucleinopathies. Independent researchers reviewed cohort, observational, longitudinal, and epidemiological studies from EMBASE, Web of Science, CINAHL, and Google Scholar. Results From an initial 4,986 titles, 11 studies met the inclusion criteria to date, comprising 9 focused on phenoconversion and 2 on prognosis. All studies specifically addressed Dementia with Lewy Bodies. Preliminary findings indicate that a lower heart rate response to orthostatic change is predictive of phenoconversion to Dementia with Lewy Bodies, while severe orthostatic hypotension is associated with reduced survival. However, the studies reviewed to date are heterogeneous and generally limited by small sample sizes. The remainder of the review will systematically examine other subtypes of alpha-synucleinopathies, as previously outlined. A critical synthesis of these studies will be presented to address the research questions. Conclusion The exact relevance of cardiovascular autonomic dysfunction as a prognostic marker and predictor of phenoconversion in alpha-synucleinopathies is unclear. By completing our systematic review, we hope to add clarity to these important questions, particularly in the era of alpha-synuclein biomarkers and potential disease modifying therapies.