Autonomic nervous system dysregulation in neurodegenerative diseases: Bridging brain and heart.

Abstract

Autonomic nervous system (ANS) dysregulation is commonly observed in a class of neurodegenerative disorders known as α-synucleinopathies including Parkinson's disease (PD), Dementia with Lewy Bodies, Multiple System Atrophy (MSA), and Pure Autonomic Failure. The ANS controls involuntary functions such as heart rate, blood pressure, digestion, and respiratory rate, and its disruption can significantly impact patients' quality of life. In neurodegenerative disorders, damage to brain regions that regulate the ANS, such as the brainstem and hypothalamus, leads to impaired autonomic functions. The autonomic nervous system regulates heart function by balancing sympathetic and parasympathetic activity. The sympathetic branch increases heart rate and contractility during stress, while the parasympathetic branch slows heart rate during rest. This dynamic control ensures optimal heart function, adjusting to physiological demands and maintaining cardiovascular stability. In Parkinson's disease and Dementia with Lewy Bodies disorder, degeneration of dopaminergic neurons affects the sympathetic and parasympathetic branches of the ANS, contributing to cardiovascular dysfunction symptoms like orthostatic hypotension, postprandial hypotension, nondipping, and supine hypertension. In Multiple System Atrophy (MSA), autonomic nervous system dysfunction disrupts heart regulation, leading to severe cardiovascular issues such as orthostatic hypotension, abnormal heart rate, and impaired blood pressure control. These autonomic disturbances increase the risk of fainting, cardiovascular instability and contribute to significant morbidity in MSA patients. The cardiac autonomic function is assessed through some tests like heart rate variability (HRV), isometric handgrip test, orthostatic test, deep breathing tests, baroreflex sensitivity test, and Valsalva manoeuvre which evaluate the balance between sympathetic and parasympathetic nervous system activity. These assessments help identify autonomic dysfunction, which can indicate underlying conditions such as neurodegenerative diseases or cardiovascular disorders.