Dr James Parkinson, in 1817, first described a condition based on observation of motor features ranging from shaking to postural instability (Parkinson, 1817), later regarded as Parkinson’s disease (PD) by Jean-Marie Charcot. Despite this initial account also including details of non-motor symptoms (NMS) such as, pain, sleepiness, and dysautonomia, PD has been, and continues to be, regarded as primarily a motor syndrome. However, decades later, research has established that NMS are an integral part of PD, with NMS burden negatively impacting patient quality of life as these symptoms are present from the prodromal to late palliative stages (Abbott et al., 2001, Abbott et al., 2005, Ross et al., 2008, Savica et al., 2010, Schapira et al., 2017, Shiba et al., 2000). Recent advances in our understanding of the pathophysiological basis of PD underpins a scenario whereby PD incorporates multi-neurotransmitter deficits, resulting in central and peripheral nervous system dysfunction. As such, PD is now regarded more as a syndrome rather than a single disease entity (Titova, Padmakumar, et al., 2017). With the development of essential evaluating tools such as the NMS Scale (NMSS) and the NMS Questionnaire (NMSQuest) (Chaudhuri et al., 2007, Martinez-Martin et al., 2011), we have become increasingly aware of the prevalence and burden posed by NMS in people with Parkinson’s (PwP). We can now investigate the NMS burden in the disease progression, with certain NMS, such as sleep dysfunction, dysautonomia, and neuropsychiatric symptoms (expanded on in Chapter 2), being independent predictors (Santos-García et al., 2021).

Recognising the clinical heterogeneity of Parkinson’s, Sauerbier and colleagues (2016) proposed that NMS in PD could be clinically categorised into seven subtypes (Sauerbier, Jenner, et al., 2016; Sauerbier, Qamar, et al., 2016): Park-pain, Park-sleep and Park-autonomic are 3 such subtypes, and in this chapter we provide a granular description of each along with suggestions for personalised bespoke therapies.

PD is a heterogeneous condition, both clinically and neurochemically, and the relative importance of different neuronal pathways and transmitter systems appear to show intra-patient differences changing with disease stages (Dulski et al., 2022, Huang et al., 2019, Rodriguez-Sanchez et al., 2021, Sauerbier et al., 2016, Titova and Chaudhuri, 2018, Zhang et al., 2019). In order to address this heterogeneity, clinical phenotyping combined with data driven approaches to delineate symptom dominant subgroups, both motor and non-motor, can be used and these subtypes could form the basis of subtype-specific therapies and aid in the delivery of personalised medicine (Titova, Qamar, et al., 2017). Currently, several non-motor dominant subtypes have been described (Fig. 1). Several of these were based on e.g. multi-partition clustering methods and cluster analyses, showing clusters around impulse control problems, overall non-motor symptoms, presence of dyskinesias and psychosis, fatigue, axial symptoms and motor fluctuations, autonomic dysfunction, depression, and excessive sweating (Rodriguez-Sanchez et al., 2021), and also the association with motor symptoms (Mu et al., 2017). In addition, clinically defined subtypes exist which have been suggested to link to noradrenergic, cholinergic, serotonergic changes and could hold relevance for specification of subtype specific treatments (Marras et al., 2020, Sauerbier et al., 2016, Titova et al., 2017). Based on this approach, dopaminergic pathway involvement remain the basis for PD symptoms, but with major contributions from other neurotransmitter systems, such as acetylcholine, noradrenaline and serotonin, which are considered subtypes of PD dependent on dominant symptoms (Titova and Chaudhuri, 2018, Titova et al., 2017). Here, we describe three of these subtypes/endophenotypes in more detail.