Parkinson’s disease (PD) is a progressive debilitating disease where continuous objective measurement (COM) can provide unique opportunities for improving symptom control. The global prevalence is 1–2 cases per 1000 population, or approximately 1–2% of those aged 60 years and older [1, 2]. PD affects many regions of the brain but damage to neural elements involved in dopaminergic neurotransmission [3] results in a number of motor and non- motor symptoms that respond to therapies with subsequent improvement in quality of life [4, 5]. The motor symptoms of PD bradykinesia, tremor, and rigidity are well known [6]. Bradykinesia is the cardinal diagnostic sign of PD and reflects impaired dopamine transmission. Thus measuring and treating bradykinesia can result in an improvement in other, dopamine responsive symptoms, including non-motor features of PD. [7,8,9,10] The main treatment of impaired dopamine transmission is levodopa [2]. Initially levodopa provides sustained benefit in treating PD symptoms but over time the duration of benefit of each dose becomes progressively shorter [11]. The clinical reemergence of bradykinesia and other motor and non-motor features are typically referred to as OFF periods or episodes. The improvement in symptoms between each dose is progressively shortened and can reach less than 2–3 h. In addition to this shortening of benefit from each dose, some people with PD (PwP) experience unreliability in the time to benefit and extent of benefit of each dose and even failure to gain any benefit from a dose (i.e., no ON period or dose failures). Collectively, variability in response to levodopa due to shortening and/or unpredictability of benefit are known as fluctuations. Involuntary movements known as dyskinesia frequently emerge after motor fluctuations begin and can be caused by excess, dysregulated dopaminergic transmission. After 5 years of disease [1, 3, 12, 13], approximately 50% of PwP can develop bradykinetic fluctuations and dyskinesia. Motor fluctuations and dyskinesia are the motor manifestations of reduced or excess (respectively) dopamine transmission, which also cause significant non-motor fluctuations [14].
Treatment of bradykinetic motor fluctuations [15] and dyskinesia depend on the PwP recognizing their presence and providing a history. However, PwP frequently under recognize wearing-off [16,17,18], bradykinesia and dyskinesia [19]. Many PwP have a new “perceived normal” where they may assume their uncontrolled symptoms are normal or uncorrectable [20]. Dyskinesia can be confused with tremor and bradykinesia can be attributed to tiredness rather than diminishing benefit from treatment. Additionally, PwP with declining cognitive function may also have difficulty attributing the emergence of symptoms to timing of medications. Symptom diaries are often used in clinical trials but the recording of signs and symptoms may be delayed to a more convenient time leading to potential recall bias [21,22,23]. In routine clinical practice, patient diaries are impractical and are not commonly used. For the patient (and caregiver), the challenge is in accurately and objectively recording and sharing this information effectively to optimize the decisions made based on the clinical visit. Thus, the management of levodopa dosing to alleviate or lessen ‘off’ time remains a challenge, since the reporting of ‘off’ time is subjective and varies from patient to patient.
Objective measurement offers an alternative to diaries that solves a dilemma for the patient and the clinician by capturing data during activities of daily living in the home environment. This not only relieves the burden for the patient on recalling events over the past few months, remembering to record the information but also in trying to articulate to their treating physician in a 15-min clinic visit. For the clinician it provides continuous objective information that can be easily interpreted in the nomenclature of PD. This can help to facilitate expeditated treatment to optimize patient outcomes.
Ambulatory continuous objective measurement (COM) technologies have been developed to overcome the problems encountered in self-reporting of dopamine responsive symptoms.
The Personal KinetiGraph® (PKG®) Movement Recording System is a new COM technology that provides scores of bradykinesia, dyskinesia, motor fluctuations, tremor, as well as immobility as a proxy for daytime sleepiness. One of the major advantages of a PKG device is that it is worn during routine activities and the PwP does not have to remember to perform specific tasks or record their activities during use. The PKG algorithms were designed to augment clinicians’ assessment of bradykinesia and dyskinesia and their assessment of the effects of therapy [24,25,26,27,28,29,30]. Having received regulatory clearance for PD patient use in Australia, Europe [31], and the United States [32], the PKG system is now used in routine patient care with over 35,000 PKGs having been performed worldwide [27].
The data collected by the PKG system is stored for research purposes in regional and global databases after de-identification. The de-identified PKG database contains measures of bradykinesia, dyskinesia, percent of time immobile, and percent of time in tremor, number of days worn by the PD patient, and basic demographic data including country of PD patient origin. When COM became available in other conditions, it inevitably led to the establishment of measurements that represent the boundary between subjects whose condition was adequately controlled and those in whom further therapeutic intervention would be in the patients’ best interest. These measurements thus become a therapeutic target and invite terminology such as “good control” of symptoms when target has been reached and “poor control” when it has not been attained. These targets are often based on several factors including physiology (i.e., values for the general population), evidence of improved quality of life or other outcome and economic/iatrogenic costs. These may shift over time as evidence changes. Targets for hypertension are a useful example. Recent publications discuss targets that have been set using a combination of expert opinion, normal physiology and empiric evidence with the expectation that research will further refine and modify these targets [33, 34]. Thus, it became possible to use these targets compared to scores in the PKG database to describe the proportion of people with bradykinesia and dyskinesia above these published target ranges. The usefulness of this provides clinicians with an objective measurement tool to more readily identify times of the day where PD treatments can be optimized to the benefit of PwP.
There is important evidence showing that increasing levels of bradykinesia, fluctuations and dyskinesia are related to health-related quality of life (HRQOL) and costs [4, 5, 35]. A recent study from the UK demonstrated that the average annual costs increased from £25,630 for those who spend less than 25% of waking hours in the off state compared to £62,147 for patients spending more than 75% of time in the off state [36]. A recent US study on the economic burden of PD estimated an incremental annual additional $24,439 to treat PD compared to matched subjects without PD in 2017 [37]. The same study showed a large percentage of PwP have experienced at least one OFF state in the past year (63.2%) [37].