The Use of the CUE1/CUE1+ Device in People With Idiopathic Parkinson's Disease and Related Disorders: A Feasibility Study

Parkinson's disease (PD) may be the fastest growing neurodegenerative disease in the world (Bloem et al., 2021). Pathologically, it is characterised by the loss of the dopaminergic neurons within the substantia nigra pars compacta (SNc) and other pigmented nuclei of the brainstem. At present, the cost of healthcare for the estimated 145,000 people living with PD in the United Kingdom is over £728 million per year rising to a total economic impact of £3.6 billion (Weir et al. 2018). If current projections are correct of people with PD, this will double by 2040 (Dorsey et al. 2018), consequently the figure may exceed £7.2 billion. Most people affected are 60 years or above. However, there are many people who are diagnosed at a younger age. Common clinical manifestations of PD include a range of both motor (e.g., bradykinesia, rigidity, tremor, and postural instability) and non-motor (e.g., fatigue, psychiatric and behavioural disturbances, autonomic dysfunction, cognitive impairment, sleep dysfunction and olfactory loss) features.

The motor features can be present anywhere in the body. Some of the common features are lack of facial expression, low volume speech, stiffness and slowness of movements. Further, gait and balance are often affected. People with PD tend to have a festinating gait, and/or experience postural instability with or without freezing of gait (FOG) which may occur when initiating walking, standing from sitting, turning, and passing through narrow passages or certain circumstances such as approaching a destination (Nutt et al., 2011) or dual tasking (DT) (Bloem et al., 2000; Jacobs et al., 2014; Isaacson et al., 2018). Postural instability, gait problems and FOG may significantly affect a person's ability to perform ADL, increase their falls risk (Muslimovic et al., 2008; Lamont et al., 2017) and reduce their quality of life (QoL). Approximately 70% of people with PD will fall in a year period which can often result in serious consequences including injuries (e.g., fractures and traumatic brain injury) which further increase morbidity, mortality, and healthcare and personal costs (Farombi et al., 2016).

Currently, there is no cure for PD or treatment options available that can slow down the progression of this condition. However, all people with PD are provided options to treat the signs and symptoms of the condition to support their ability to participate in ADL that are meaningful to them (Huber et al., 2011). First line therapy, the dopaminergic medications, have some impact on motor symptoms in PD but rarely get people back to a "normal" state (Killane et al., 2015). People often remain significantly limited in their ADL during 'OFF' state but even during 'ON' state, many features of PD do not respond adequately despite optimal pharmacotherapy (Shukla et al., 2012). Moreover, the usage of medication often has serious side effects, particularly in older adults. The average person living with PD may be taking nine doses of medication a day (Grosset et al., 2007). Thus, drug resistance is another concern and dose limiting side effects is a barrier to successful deployment of pharmacotherapy (Killane et al., 2015). This issue increases with disease progression because neurodegeneration progressively involves non-dopaminergic brain areas. As a result, various non-pharmacological, non-invasive interventions have been developed to manage sensory dysfunction, a major problem in people with PD, associated with PD symptoms (Conte et al., 2013). Cueing and vibrotactile sensory stimulation are two such examples that have been used to modulate sensory dysfunction in people with PD, especially the sensorimotor integration problems.

Cueing is a mechanism of applying an external temporal or spatial stimulus to facilitate movement initiation and continuation and it can be somatosensory, auditory, attentional or visual (Nieuwboer et al., 2007; Muthukrishnan et al., 2019). It is reported to work by shifting habitual motor control to goal directed motor control (Redgrave et al., 2010). Many studies have demonstrated that cueing helps to improve postural control, balance, FOG (van Wegen et al., 2006; Nieuwboer et al., 2007; Munoz-Hellin et al., 2013; Spaulding et al., 2013; Muthukrishnan et al., 2019), as well as DT performance in activities involving the upper (Heremans et al., 2016; Park & Kim, 2021) and lower (Rochester et al., 2007; 2009; 2010 (a); 2010(b); Fok et al., 2010; Mak et al., 2013; Beck et al., 2015; Chomiak et al., 2017; Mancini et al., 2018; Stuart & Mancini, 2020) limbs in people with PD. However, many cueing modalities used for the research purposes in the laboratory environments cannot be easily replicated in people's homes. Thus, a recent narrative review recommends the development of cueing wearable systems that can be used at home or in the community to improve gait and posture in PD (Muthukrishnan et al., 2019).

Interventions utilising vibrotactile sensory stimulation in PD can be split into two main groups: a) whole body vibrotactile stimulation and b) focused (e.g., targeted) vibrotactile stimulation. The results on the effectiveness of whole body vibrotactile stimulation on sensory dysfunction and motor symptoms are mixed with a large variation being reported from none to small improvement on motor symptoms, balance, gait and mobility (Dincher et al., 2019). On the other side, focused vibrotactile stimulation which is a non-invasive neuromodulation technique used by somatosensory cues (e.g., tactile/somatosensory cueing) to apply gentle vibrations to focal joints in the body may have a more positive and consistent effect (Basta et al., 2011; Pfeifer et al., 2021). Trials which include cylindrical vibration devices on the triceps (Pereira et al., 2016), a vibrotactile waistband around the abdomen in FOG (Goncalves et al., 2018), vibrotactile insoles to reduce falls (Otis et al., 2016) and a proprioceptive stabiliser on postural instability (Volpe et al., 2014) show promising results. The CUE1 is a non-invasive medical device which utilises a metronome-like pulsed vibration which represents both auditory and somatosensory low frequency cueing and high frequency focused vibrotactile stimulation to help improve motor task performance in people with PD (Tan et al., 2021; Ong et al., 2022; Wilhelm et al., 2022). It is a CE marked and an MHRA registered non-invasive medical device.