Non-motor complications in late stage Parkinson’s disease: recognition, management and unmet needs

ABSTRACT

Introduction: The burden of non-motor symptoms (NMS) is a major determinant of health-related quality of life in Parkinson’s disease (PD), particularly at its late stage.

Areas covered: The late stage is usually defined as the period from unstable advanced to the palliative stage, characterized by a combination of emerging treatment-resistant axial motor symptoms (freezing of gait, postural instability, falls and dysphagia), as well as both non-dopaminergic and dopaminergic NMS: cognitive decline, neuropsychiatric symptoms, aspects of dysautonomia, pain and sleep disturbances (insomnia and excessive day-time sleepiness). Here, the authors summarize the current knowledge on NMS dominating the late stage of PD and propose a pragmatic and clinically focused approach for their recognition and treatment.

Expert opinion: The NMS progression pattern is complex and remains under-researched. While dopamine-dependent NMS may improve with dopamine replacement therapy, non-dopamine dependent NMS worsen progressively and culminate at the late stages of PD. Furthermore, some PD specific features could interact negatively with other comorbidities, multiple medication use and frailty – the evaluation of these aspects is important in the creation of personalized management plans in the late stage of PD.

KEYWORDS:

• Parkinson’s disease
• non-motor symptoms
• late stage
• quality of life
• cognition
• neuropsychiatric symptoms
• dysautonomia
• pain

Acknowledgments

The authors would like to thank the editorial support of Ms Aleksandra Podlewska for her help with design of figures as well as the Parkinson’s disease Non-motor Study Group (NMSG) of the International Parkinson’s and Movement Disorders Society. Authors, KK, LB, AAC and VB are part of the subtheme research groups of the NMSG.

Declaration of interest

K Rukavina is supported by NIHR BRC and has received a consultancy fee from Valid Insight and Britannia. KR Chauduri has acted on advisory board for AbbVie, UCB, GKC, Bial, Cynapsus, Novartis, Lobsor, Stada, Medtronic, Zambon, Profile, Sunovion, Roche, Therevance, Scion and Britannia, and has received honoraria for lectures from AbbVie, Britannia, UCB, Mundipharma, Zambon, Novartis, Boeringer Ingelheim, and grants (Investigator Initiated) from Britania Pharmaceuticals, AbbVie, UCB, GKC, Bial, Aacdemic grants: EU, IMI EU, Horizon 2020, Parkinson’s UK, NIHR, PDNMG, EU (Horizon 2020), Kirby Laing Foundation, NPF, MRC, Welcome Trust. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Burden of non-motor symptoms (NMS) is major determinant of health-related quality of life in Parkinson’s disease (PD)

• The heterogeneity of the clinical phenomenology in the late stage of PD arises from overlapping neurotransmitter involvement (not just dopamine) as well as amyloid and tau deposition in addition to alpha synuclein

• Late stage is dominated by treatment-resistant axial motor symptoms (freezing of gait, postural instability, falls and dysphagia) along with aggravating burden of dopaminergic and non-dopaminergic NMS, including cognitive decline, neuropsychiatric symptoms, aspects of dysautonomia, pain and sleep disturbances

• A simple, time efficient and pragmatic assessment comprising motor and NMS in a busy clinic could be performed using the Martinez-Martin & Chaudhuri clinical grading based on the Hoehn and Yahr (HY) staging for motor symptoms coupled with staging of the non-motor burden using the NMSQuestionnaire (NMSQuest)

• Optimal management of late stage PD requires a holistic, patient-centered approach with a personalized pharmacological and non-pharmacological therapeutic strategy tackling specific NMS and motor symptoms