Non-motor Symptoms in Parkinson’s Disease – Impact, Recognition and Management
K Ray Chaudhuri
Professor of Movement Disorders; Director, National Parkinson Foundation Centre of Excellence, Kings College, Denmark Hill Campus, London, UK
Professor Chaudhuri considered that non-motor symptoms (NMS) were an integral part of Parkinson’s disease (PD) and the leading cause of poor quality of life (QoL) in PD patients. The association of NMS with motor PD has been recognised since the disease was first identified – in his original essay on PD, James Parkinson described several non-motor issues, including sleepiness and autonomic dysfunction.1 NMS often pre-date motor symptoms by 10–15 years2–4 and research on this topic has revealed that late onset hyposmia and rapid eye movement sleep disorder are possible pre-motor markers of motor PD.5 In terms of the patient experience, evidence now suggests that it is the total ‘burden’ of NMS, not just the occurrence of individual NMS such as depression, that is the major determinant of health-related QoL (HRQoL) in PD patients.6 In the Sydney multicentre study, long-term follow-up of PD patients for 20 years found that they were often troubled to a greater extent by NMS than by motor symptoms.7 As a result, PD is now considered by some to be a neuropsychiatric disorder.
NMS are highly prevalent in PD patients and several studies have reported that almost all patients (>98 %) report some symptoms.3,8 Data accumulated from eight international studies including over 2,500 PD patients indicate that most PD patients will report at least eight different NMS when assessed using the validated Non-Motor Symptoms Questionnaire: NMSQuest.9
An evolving area of research in PD relates to different genetic forms of PD and how they relate to non-motor signs. At least 18 mutations in the synuclein alpha (SNCA) gene, one of the PARK family of genes known to be associated with PD, have been described. Analysis of SNCA missense mutations and multiplications, albeit in a relatively small number of PD patients, has suggested that dementia is a marker for this genetic form of PD.10 LRRK2 (leucine-rich repeat kinase 2, another of the PARK gene family) mutations on the other hand are commonly associated with sleep disorders. LRRK2 mutation carriers often have a marked degree of insomnia, including disturbed sleep patterns with repeated wakening, a troubling form of restless leg syndrome and a high frequency of early morning ‘off’ periods. Variations in the GBA (glucosidase beta acid) gene are commonly seen in PD and parkinsonism. GBA mutations seem to be associated with autonomic issues, dementia and hallucinations, and patients often have a high degree of anxiety and depression. These emerging data on the non-motor markers of genetic subtypes of PD may help refine treatment strategies in the future.