The underrated value of non-motor symptoms of Parkinson’s disease in making diagnostic and treatment decisions

Parkinson's disease (PD) is identified clinically by the presence of prominent motor signs; however, in recent years there has been growing recognition of non-motor symptoms (NMS) causing a similar or even greater impact on patients' quality of life. Wide spectrum of non-motor problems includes cognitive, neuropsychiatric, sensory, gastrointestinal, urinary, and cardiovascular issues, among others. Some of them are integral parts of the disease, while others may be side effects of applied therapies. Non-motor symptoms like hyposmia, cognitive decline, autonomic symptoms, and sleep disorders may indicate specific PD subtypes or signal prodromal disease before the appearance of motor parkinsonian signs. The burden of NMS increases with disease progression, but early presence of autonomic failure, hallucinations, or cognitive impairment points toward atypical parkinsonian syndromes. Non-motor symptoms significantly limit the possibility of applying certain pharmacological, surgical, and infusion therapies. Orthostatic hypotension (OH), impulse control disorder, or increased sleepiness are contraindications for use of dopamine agonists (DAs) and apomorphine infusion. Medications with anticholinergic properties may exacerbate existing cognitive and gastrointestinal problems. Moreover, neuropsychiatric problems with dementia, depression, and hallucinations may exclude patients from receiving deep brain stimulation (DBS), apomorphine, and levodopa/carbidopa or foslevodopa/ /foscarbidopa (LDp/CDp) infusions. While NMS are not routinely assessed by diagnostic criteria and standard tools during PD therapy, they should be carefully evaluated at every step of PD management. In this review, we summarize the underrated role of NMS in PD diagnosis and therapy planning and discuss potential measures to better address them.