Clinical Review

The Nonmotor Symptoms of Parkinson’s Disease: Update on Diagnosis and Treatment



From the Department of Neurology, Movement Disorders Division, University of Pittsburgh Medical Center, Pittsburgh, PA.


  • Objective: To review the prevalence, diagnosis, and treatment of the nonmotor symptoms (NMS) associated with Parkinson’s disease (PD).
  • Methods: Narrative review of the literature.
  • Results: The NMS of PD are becoming increasingly recognized as having a critical role in the impact of this neurodegenerative movement disorder. This has led to significant investigative efforts to identify new or better NMS therapies. The preponderance of PD patients will be diagnosed with 1 or multiple NMS during the course of their disease, with many of these symptoms occurring months or even years prior to receiving the PD diagnosis. Despite the high prevalence and impact on disease burden, NMS often go undetected due to a lack of reporting by patients or insufficient interrogation by physicians. Further complicating NMS management is that only a few therapies have the level of evidence needed to support their use in the treatment of NMS.
  • Conclusion: The practitioner needs to be aware of NMS and conduct thorough patient questioning in order to recognize, diagnose, and address NMS in PD patients.

Parkinson’s disease (PD) is a neurodegenerative movement disorder with an estimated prevalence of 1% to 2% among the population over the age of 65 years [1]. Recognition and clinical diagnosis of PD is primarily made based on the cardinal motor features, including rigidity, tremor, bradykinesia, and postural instability. The motor symptoms are neuropathologically associated with accumulation of alpha-synuclein with Lewy body formation and neurodegeneration of the nigrostriatal dopamine system. Postmortem evaluation of the brains of PD patients has revealed more widespread degeneration in nondopaminergic systems, including several brainstem nuclei (raphe nucleus, locus ceruleus, dorsal vagal nucleus), limbic and neocortical structures, as well as the peripheral autonomic system [2,3].

The nonmotor symptoms (NMS) of PD are the clinical manifestations of this extensive degeneration, which suggests that NMS are intrinsic and fundamental features of PD. NMS are exceedingly common, and up to 90% of PD patients will experience nonmotor features, including depression, anxiety, sleep disturbances, cognitive impairment, and dysautonomia [4,5] ( Table).

NMS have a greater impact on quality of life as compared to the motor symptoms [6,7], but are frequently underrecognized [8]. Evidence suggests that unless there is systematic and specific interrogation by practioners, NMS will elude recognition [9–11]. Recognizing NMS as part of PD is complicated by the fact that these symptoms are common in the general population and not specific for PD [12,13]. NMS can occur at any stage of the disease and may predate diagnosis [12], although as PD progresses the NMS become more prevalent, with a greater impact on health care costs and institutionalization rates than motor features [14,15].

Neuropsychiatric Symptoms


Epidemiology and Diagnosis

Depression is one of the most common neuropsychiatric manifestations observed in PD patients, with prevalence reports between 4% and 72%, though likely to be closer to 30% to 45% [16–20]. The severity of depression in the PD population has been shown to be greater than in patients with matched chronic disabilities [21,22] and also greater than in the general population over the age of 65 years [23]. The onset of depression can occur at any stage of the disease, even predating the diagnosis. Additionally, depression has more than twice the impact on health status than motor symptoms [24].