The Brain Under the Influence of Non-motor Signs in Parkinson Disease: Neurological, Pharmacological and Physiotherapy Related Correlations

Abstract

Parkinson’s disease (PD), traditionally considered a motor disorder, also manifests by a wide range of non-motor symptoms (NMS) such as cognitive, mood, autonomic, gastrointestinal, and sensory disturbances, significantly impacting quality of life and complicating diagnosis and management, both in terms of pharmacology and physiotherapy. Degeneration in noradrenergic and serotonergic systems may be key contributors to NMS. These symptoms can appear early, may sometimes precede motor signs, and require individualized assessment and care. Investigations such as MRI of the locus coeruleus, EEG, retinal imaging, and blood-based panels are under investigation to better characterize NMS and disease heterogeneity. Along this interest, heart rate variability (HRV) is a non-invasive marker of autonomic dysfunction in PD, intensively studied nowadays, since it correlates to central and peripheral nervous system changes, also linking autonomic impairment to cognitive decline and cerebrovascular injury. However, HRV interpretation is challenged by methodological variability, medication effects, as well as patient heterogeneity. Pharmacological management of NMS is further complicated by drug interactions, side effects, and multisystem involvement, while physiotherapy must often adapt to challenges coming from autonomic instability, medication timing, and exercise modality. This narrative review aims to provide insight among the management of non-motor manifestations in PD, with emphasis on HRV’s influence.