Heart rate variability during sleep in synucleinopathies: a review

Synucleinopathies are a group of neurodegenerative diseases characterized by abnormal accumulations of insoluble alpha-synuclein in neurons or glial cells. These consist of Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Moreover, idiopathic REM sleep behavior disorder (iRBD) is often the first manifestation of synucleinopathies, demonstrating a pathophysiological continuum. While these disorders vary in prevalence, symptom patterns, and severity, they can all include autonomic nervous system (ANS) dysfunction, which significantly reduces quality of life and worsens prognosis. Consequently, identifying abnormalities of the ANS can provide opportunities for improving quality of life through symptomatic treatments that are tailored to the individual's symptoms. An exciting development is using heart rate variability (HRV) as a non-invasive research tool for analyzing how the ANS regulates physiological processes. HRV during sleep, however, may provide a more accurate and reliable measure of ANS activity than during wakefulness, as during awake time, ANS activity is influenced by a variety of factors, including physical activity, stress, and emotions, which may mask or confound the underlying patterns of ANS activity. This review aims to provide an overview of the current knowledge regarding sleep-related HRV in synucleinopathies and to discuss contributing mechanisms. Evidence suggests that iRBD, PD, and MSA are associated with nocturnal ANS dysfunction. Further, comparative studies indicate that the presence of RBD could exacerbate this abnormality. In contrast, no studies have been conducted in patients with DLB. Overall, this review provides new insight into the complex interplay between the ANS and synucleinopathies and underscores the need for further research in this area to develop effective therapies to improve sleep and overall quality of life in patients with synucleinopathies.