**About the Editors**

#### **Nataliya Titova**

Dr. Nataliya Titova is currently an Associate Professor and consulting Neurologist in the Department of Neurology, Neurosurgery and Medical Genetics at the Federal State Budgetary Educational Institution of Higher Education .I. Pirogov Russian National Research Medical Universityof the Ministry of Healthcare of the Russian Federation in Moscow. She graduated from Pirogov Russian National Research Medical University in Moscow and obtained her Ph.D. with a thesis on controlled cross-sectional and prospective study on clinical and neurophysiological evaluation of patients with de novo Parkinson's disease (PD). She, thereafter, trained to become a specialist in movement disorders and a parkinsonologist. Dr. Titova is also part of the overseas research faculty at the Parkinson Foundation International Parkinson Centre of Excellence at Kings College Hospital in London. She is an active teacher and researcher in the field of PD and related conditions and has a special interest in PD non-motor pathophysiology, genetics, and biomarker-driven assessment of natural history and endophenotypes. She is leading an international programme on developing strategies for personalised medicine in PD.

#### **K. Ray Chaudhuri**

Professor K. Ray Chaudhuri is Professor of Neurology/Movement Disorders at King's College Hospital and King's College London and the Medical Director of the Parkinson Foundation International Centre of Excellence at King's College.

He is internationally known for pioneering modern care for people with Parkinson's particularly advanced therapies in addition to care for restless legs syndrome. He is the founding Chairman of the International Movement Disorders Society Non-motor Study Group and member MDS-ES Education and palliative care committee and ex Chair of the MDS Membership and Public Relations committee as well as member MDS congress scientific programme committee (2013–2017).

He is the founding and consulting editor and ex editor-in-chief of the Nature group *Nature* Parkinson's journal (2020 Impact Factor 8.8), as well as Guest Editor for Special Issues of Frontiers in Neurology, *Journal of Personalised Medicine* (Impact Factor 4.8), Movement Disorders in Older Adults (Geriatrics) and Journal of Parkinson's Disease, reviewer for all mainstream Movement Disorders journals as well as JAMA, Neurology, Annals of Neurology, BMJ, Brain, Lancet and JNNP.

He won the Andrew Wilson Prize for services to RLS patients by RLS:UK, William Koller Memorial Fund Award by MDS, the 2018 Van Andel award in the USA for outstanding nonmotor research contribution in the field of nonmotor Parkinson, as well as NIHR/Royal College of Physicians London award for outstanding research leadership in 2017.

In 2020, he was elected as lead for Equality Diversity charter for NIHR London South Applied Research Collaboration (ARC) and was elected as a Honorary Member for the Movement Disorders Society in 2021. In 2022, he was awarded UK NHS Gold merit clinical impact award and is currently ranked 6th in the world and top from the UK for publications related to Parkinson's (Expertscape-Parkinson's disease).

## *Editorial* **The Dashboard Vitals of Parkinson's: Not to Be Missed Yet an Unmet Need**

**Kallol Ray Chaudhuri 1,2,\* , Nataliya Titova 3,4, Mubasher A. Qamar 1,2 , Iulia Murăs, an <sup>5</sup> and Cristian Falup-Pecurariu 5,6**


#### **1. Commentary**

The vitals of Parkinson's disease (PD) address the often-ignored symptoms, which are considered either peripheral to the central core of motor symptoms of PD or secondary symptoms, which, nevertheless, have a key role in the quality of life (QoL) and wellness of people with Parkinson's (PwP) [1]. Unmet needs in PwP have recently been discussed, with many being related to motor symptoms and, specifically, non-motor symptoms (NMSs), which continue to pose a major challenge to PwP and their clinicians [2]. In addition, several other factors related to enablers of PD expression, progression, as well as co-morbidities and co-medication issues compound the wellness of PwP and we proposed all PwP to have a dashboard, whereby clinical assessment for these symptoms must be noted and managed as bespoke to the individual person, a key element in modern personalized medicine for PD [3,4].

The key elements of the vitals to form a dashboard for PwP are shown in Figure 1. These include the essential motor assessment, which is completed in almost all clinics as the initial evaluation in consultations. Motor function can be graded by clinical examination and assigning the Hoehn and Yahr (H&Y) staging [5], which, despite its clinimetric drawbacks, continues to be the most widely used clinical assessment for tangible and real-life motor assessment of PD and has stood the test of time. If time permits and there is capacity, then detailed motor examinations are possible using the Scales for Outcomes in PD (SCOPA)-motor [6], Movement Disorder Society Unified PD Rating scale (MDS-UPDRS) [7], or even the older UPDRS parts 3 and 4 [8]. In the future, PD-validated wearable monitoring scores with sensors, such as Parkinson kinetograph (PKG), could be added [9,10].

Then, there is the burden of NMS assessments, which can be carried out and graded using either the validated NMS Questionnaire (NMS Quest) or, if time permits, utilizing the PD-NMS scale (NMSS) [11–14]. NMS burden (NMSB) should be performed for every patient and graded, alongside the patients and their caregivers, rating their top named bothersome NMS. NMSB is contributed to by a range of NMS, from cognitive issues, neuropsychiatric problems, such as depression, apathy, and anxiety, to sleep dysfunction, hyposmia, bladder, bowel, and upper gastrointestinal dysfunction, such as the dribbling of saliva. NMSB has a direct correlation with QoL and a guide to using the NMS Quest in the clinic has also been published. NMSB score should be integral to the dashboard and ideally measured on a yearly basis [15].

**Citation:** Chaudhuri, K.R.; Titova, N.; Qamar, M.A.; Mur˘as,an, I.; Falup-Pecurariu, C. The Dashboard Vitals of Parkinson's: Not to Be Missed Yet an Unmet Need. *J. Pers. Med.* **2022**, *12*, 1994. https://doi.org/ 10.3390/jpm12121994

Received: 22 November 2022 Accepted: 30 November 2022 Published: 2 December 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

ideally measured on a yearly basis [15].

**Figure 1.** A diagram of the essential "vitals" to be considered in Parkinson's disease which should form a dashboard of symptoms to be considered and managed in every person with Parkinson's. NMSB non-motor symptom burden; H Pylori Helicobacter pylori; P Gingivalis porphyromonas gingivalis; CPS comorbidity polypharmacy score. **Figure 1.** A diagram of the essential "vitals" to be considered in Parkinson's disease which should form a dashboard of symptoms to be considered and managed in every person with Parkinson's. NMSB non-motor symptom burden; H Pylori Helicobacter pylori; P Gingivalis porphyromonas gingivalis; CPS comorbidity polypharmacy score.

of saliva. NMSB has a direct correlation with QoL and a guide to using the NMS Quest in the clinic has also been published. NMSB score should be integral to the dashboard and

Vision is a critical aspect of living with PD and is rarely formally addressed in a PD clinic. A range of visual problems can occur in PD and these have been explored in several studies [16–20]. Vision assessment is important for PwP who continue to drive and, in this respect, night blindness (nyctalopia) and convergence insufficiency are important. Subsequently, a patient may have significant discomfort related to dry eyes (xeropthalmia), which is treatable with eye drops as well as glaucoma. The NMS Quest also allows for declaration of diplopia, which is common in PD and may be related to dyskinesias or convergence insufficiency. Nyctalopia may be related to vitamin A deficiency and may require night-time bedroom lighting to prevent falls at night-time should the patient need to get out of bed, for instance, to go to the toilet. Significant issues need a referral to an ophthalmologist [21]. Vision is a critical aspect of living with PD and is rarely formally addressed in a PD clinic. A range of visual problems can occur in PD and these have been explored in several studies [16–20]. Vision assessment is important for PwP who continue to drive and, in this respect, night blindness (nyctalopia) and convergence insufficiency are important. Subsequently, a patient may have significant discomfort related to dry eyes (xeropthalmia), which is treatable with eye drops as well as glaucoma. The NMS Quest also allows for declaration of diplopia, which is common in PD and may be related to dyskinesias or convergence insufficiency. Nyctalopia may be related to vitamin A deficiency and may require night-time bedroom lighting to prevent falls at night-time should the patient need to get out of bed, for instance, to go to the toilet. Significant issues need a referral to an ophthalmologist [21].

Bone health is an integral aspect of Parkinson's wellness and relates to a very high incidence of osteoporosis or osteopenia in PD and related risk of fractures with falls and frailty as well as subsequent risk of hospitalization. A global longitudinal study of osteoporosis in women, the GLOW study, reported PD to be the strongest and most robust contributor to risk of fractures compared with other studied factors [22]. Motor dysfunction, frailty, gait impairment and freezing, postural instability, diphasic or troublesome dyskinesias and falls, polypharmacy, and reduced bone density contribute towards the increased risk of fracture in PD [23–26]. Vitamin D deficiency along with disease duration and severity, age, and low body mass index (BMI) with secondary hyperparathyroidism may also contribute to low bone density and need to be evaluated in all PwP periodically and added to the dashboard [22]. Bone health is an integral aspect of Parkinson's wellness and relates to a very high incidence of osteoporosis or osteopenia in PD and related risk of fractures with falls and frailty as well as subsequent risk of hospitalization. A global longitudinal study of osteoporosis in women, the GLOW study, reported PD to be the strongest and most robust contributor to risk of fractures compared with other studied factors [22]. Motor dysfunction, frailty, gait impairment and freezing, postural instability, diphasic or troublesome dyskinesias and falls, polypharmacy, and reduced bone density contribute towards the increased risk of fracture in PD [23–26]. Vitamin D deficiency along with disease duration and severity, age, and low body mass index (BMI) with secondary hyperparathyroidism may also contribute to low bone density and need to be evaluated in all PwP periodically and added to the dashboard [22].

When assessing PwP holistically, the issue of weight is often ignored in clinical consultations, although blood pressure, height, and weight are often routinely collected in the clinic. Low body weight poses a specific challenge in PD and a low body weight When assessing PwP holistically, the issue of weight is often ignored in clinical consultations, although blood pressure, height, and weight are often routinely collected in the clinic. Low body weight poses a specific challenge in PD and a low body weight phenotype in PD, the Park-weight phenotype, has been proposed to have a high risk of dyskinesias, as well as possible links with cognitive dysfunction and hyposmia [27–29]. Weight and BMI, therefore, need to be noted at baseline in all PD cases and routinely charted for monitoring. Unexplained weight loss is a question asked in the NMS Quest and, in addition, may

be a problem with some medications, such as intrajejunal levodopa infusion, as well as those with severe dyskinesias. Unexplained weight loss coupled with rising frailty has also been linked to future cognitive dysfunction and, therefore, also may have prognostic consequences [30,31].

Gut and oral health is another important enabler of wellness and health in PD and constitutes the important "vital" aspect for the dashboard. Gut dysfunction in PD is well documented and ranges from upper gastrointestinal dysfunction, such as dysphagia and delayed gastric emptying, to constipation [32].

While many of these symptoms are flagged up in the NMS Quest and constitute part of the NMSB, some need key and focused attention as they are often ignored in clinics. These include:


Finally, there is the issue of comorbidity- and medication-related enablers of health, such as impulse control disorders (ICD) as well as medication management. Diabetes mellitus has been proposed to be a risk factor of PD and comorbid diabetes can affect PD [40–42]. Consequently, blood glucose is often listed, along with urate, as associates in the revised MDS criteria for PD, while antidiabetic drugs are being examined for possible neuroprotection in PD [43]. Diabetes is a risk factor for worsening neurodegeneration, delayed gastric emptying as well as cognitive dysfunction and, hence, should be actively listed in the dashboard [44]. Other important co-morbidities, which have been proposed as risk factors for PD, also include REM Sleep behaviour disorder (RBD), with 80% of RBD patients developing neurodegenerative diseases, such as PD [45,46]. Development of PD Dementia (PDD) has been proposed to be greater in those with higher UPDRS scores, male gender, have hypertension, and, most commonly, have a history of neuropsychiatric disorders [47]. As such, greater emphasis should be on managing cognitive and psychological disorders in PwP given the risk of significant progression in PD that can occur in these cohorts; as such, the dashboard includes MoCa and MDS NMS, both of which aid in the surveillance of the emergence and presence of psychiatric and other neurological comorbidities.

Polypharmacy is common in PD related to comorbidities and risks side effects, which includes ICD with dopaminergic drugs, specifically dopamine agonists. Withdrawal of dopaminergic drugs, specifically dopamine agonists, also needs to follow a graded pattern to avoid dopamine agonist withdrawal syndrome [48,49]. The use of dopaminergic drugs carries with it side effects, which must be reviewed in each consultation with PwP, to ensure adequate support and holistic care are provided. Side effects include ICD, which can range from hypersexuality, gambling, binge eating, or impulsively, and other side effects, including neuropsychiatric (hallucinations, delusions) and dyskinesias [50,51]. The dashboard includes assessment of these concurrently during consultation (see Figure 2). Furthermore, specific attention needs to be given to anticholinergic drugs and a reference to the anticholinergic index of all drugs being given to PwP, as these drugs should not be used in the cholinergic subtype of PD and generally can worsen cognition and gait in PD. In this respect, a comorbidity polypharmacy score (CPS), which is defined as the sum of baseline medication and all known comorbidities, may be useful, and the severity of CPS has been traditionally stratified as mild (CPS 0–7), moderate (8–14), severe (15–21), and morbid (≥22 points). Pill burden, comorbidity, and swallowing all come into play in this respect [52,53]. includes ICD with dopaminergic drugs, specifically dopamine agonists. Withdrawal of dopaminergic drugs, specifically dopamine agonists, also needs to follow a graded pattern to avoid dopamine agonist withdrawal syndrome [48,49]. The use of dopaminergic drugs carries with it side effects, which must be reviewed in each consultation with PwP, to ensure adequate support and holistic care are provided. Side effects include ICD, which can range from hypersexuality, gambling, binge eating, or impulsively, and other side effects, including neuropsychiatric (hallucinations, delusions) and dyskinesias [50,51]. The dashboard includes assessment of these concurrently during consultation (see Figure 2). Furthermore, specific attention needs to be given to anticholinergic drugs and a reference to the anticholinergic index of all drugs being given to PwP, as these drugs should not be used in the cholinergic subtype of PD and generally can worsen cognition and gait in PD. In this respect, a comorbidity polypharmacy score (CPS), which is defined as the sum of baseline medication and all known comorbidities, may be useful, and the severity of CPS has been traditionally stratified as mild (CPS 0–7), moderate (8–14), severe (15–21), and morbid (≥22 points). Pill burden, comorbidity, and swallowing all come into play in this respect [52,53].

disorders [47]. As such, greater emphasis should be on managing cognitive and psychological disorders in PwP given the risk of significant progression in PD that can occur in these cohorts; as such, the dashboard includes MoCa and MDS NMS, both of which aid in the surveillance of the emergence and presence of psychiatric and other neurological

Polypharmacy is common in PD related to comorbidities and risks side effects, which
