The Heterogeneity of Early Parkinson’s Disease: A Cluster Analysis on Newly Diagnosed Untreated Patients

Erro, Roberto; Vitale, Carmine; Amboni, Marianna; Picillo, Marina; Moccia, Marcello; Longo, Katia; Santangelo, Gabriella; Rosa, Anna De; Allocca, Roberto; Giordano, Flavio; Orefice, G; Michele, Giuseppe De; Santoro, Lucio; Pellecchia, Maria Teresa; Barone, Paolo

doi:10.1371/journal.pone.0070244

Cited by 170 publications

(162 citation statements)

References 43 publications

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“…Additionally, cluster analysis from several large early PD and untreated cohorts have all suggested specific NMS dominant or only NMS driven clustering [12][13][14]. This review aims to highlight these phenotypic variants that have been described within the rubric of Parkinson's disease.…”

Section: Why Non Motor Subtypes?mentioning

confidence: 99%

“…Erro et al have conducted a cluster analysis coupled with validated cognitive, motor and non-motor assessments in a untreated PD cohort and found 4 discrete clusters within the cohort termed benign pure motor, benign mixed motor-non-motor, non-motor dominant and motor dominant [12]. The non-motor dominant cluster reported higher urinary dysfuction and a rapid progression rate compared to the benign mixed motor, non-motor cluster.…”

Section: Evidence From Studies In Untreated Pdmentioning

confidence: 99%

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Non motor subtypes and Parkinson's disease

Sauerbier

Jenner

Todorova

et al. 2016

Parkinsonism & Related Disorders

309

212

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Word count abstract: 163 Word count manuscript: 2839 References: 30 2 AbstractNon motor symptoms (NMS) represent a significant burden in Parkinson's disease (PD) with numerous studies highlighting the importance of NMS both in "pre-motor" phase of PD as well as throughout the disease course. In part this has led the international Parkinson and Movement Disorder Society (IPMDS) task force to attempt a re-definition of PD incorporating NMS and not base the diagnosis solely on motor symptoms. While motor subtypes within PD have been recognized and researched, recent, clinical and neurobiological research suggests the existence of discrete non-motor subtypes in PD, particularly in untreated (drug naïve) and early PD patients. Several independent observers have reported specific "clusters of NMS dominant PD" using a data driven approach in early and untreated PD patients while others have reported on the burden of NMS in untreated PD and specific NMS dominant phenotypes in untreated or treated PD using observational case series based data. In this review we report on specific NMS dominant phenotypes of PD as described in the literature using clinical observational studies and address pathophysiological concepts. A proposal for several NMS subtypes are reported combining clinical reports with, where possible, evidence base supporting probable biomarkers.

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Section: Why Non Motor Subtypes?mentioning

confidence: 99%

Section: Evidence From Studies In Untreated Pdmentioning

confidence: 99%

Non motor subtypes and Parkinson's disease

Sauerbier

Jenner

Todorova

et al. 2016

Parkinsonism & Related Disorders

309

212

View full text Add to dashboard Cite

show abstract

“…In the field of personalised medicine, metabotyping may play a role by stratifying patients for the development of tailored healthcare solutions (45) . Examples of this concept are also available from the medical literature where cluster analysis has been used to identify different phenotypes for a range of diseases including chronic obstructive pulmonary disease (46) and Parkinsons disease (47) . This concept has been particularly useful for multisymtomatic and multifactorial diseases where presentation and severity of the disease can differ from one individual to the next.…”

Section: Moving From Individuals To Groups: a Novel Use Of Phenotypinmentioning

confidence: 99%

Can metabotyping help deliver the promise of personalised nutrition?

et al. 2015

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Over a decade since the completion of the human genome sequence, the promise of personalised nutrition available to all has yet to become a reality. While the definition was originally very gene-focused, in recent years, a model of personalised nutrition has emerged with the incorporation of dietary, phenotypic and genotypic information at various levels. Developing on from the idea of personalised nutrition, the concept of targeted nutrition has evolved which refers to the delivery of tailored dietary advice at a group level rather than at an individual level. Central to this concept is metabotyping or metabolic phenotyping, which is the ability to group similar individuals together based on their metabolic or phenotypic profiles. Applications of the metabotyping concept extend from the nutrition to the medical literature. While there are many examples of the metabotype approach, there is a dearth in the literature with regard to the development of tailored interventions for groups of individuals. This review will first explore the effectiveness of personalised nutrition in motivating behaviour change and secondly, examine potential novel ways for the delivery of personalised advice at a population level through a metabotyping approach. Based on recent findings from our work, we will demonstrate a novel strategy for the delivery of tailored dietary advice at a group level using this concept. In general, there is a strong emerging evidence to support the effectiveness of personalised nutrition; future work should ascertain if targeted nutrition can motivate behaviour change in a similar manner.

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“…This hypothesis was investigated in a large cohort of newly diagnosed, untreated PD patients. 15 Data were collected on demographics, motor symptoms and NMS from 100 subjects and a cluster analysis performed that allowed the identification of different subgroups of PD patients. Four distinct groups were identified that could be classified as (1) benign pure motor, (2) benign mixed motor-non-motor, (3) non-motor dominant and (4) motor dominant.…”

Section: European Neurological Reviewmentioning

confidence: 99%

Extending our Understanding of the Dopaminergic Basis of Non-motor Symptoms in Parkinson’s Disease

Korczyn

Chaudhuri²,

Laar

2015

European Neurological Review

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Parkinson's disease (PD) is primarily considered as a motor disorder but there is increasing recognition of the wide range of non-motor symptoms (NMS), such as low mood, pain, apathy, fatigue and sleep problems, which may be experienced by PD patients across the spectrum of the disease. Notably, NMS often occur before motor symptoms develop and are known to place a significant burden on health-related quality of life (HRQoL) of the person with PD. Commonly, NMS go undiagnosed by the clinician and are therefore undertreated; however, to optimise patient outcomes, both motor and non-motor aspects of PD need to be recognised and managed that it is the total 'burden' of NMS, combining frequency and severity, and not just the occurrence of individual NMS such as depression, which is the major determinant of a patient's HRQoL. Recognising the significant contribution of NMS to the total clinical picture in PD, in order to provide a more comprehensive grading of PD severity, it is now proposed that the clinical assessment of PD patients needs a combined approach using for example the validated Non-motor Symptoms Scale (NMSS) to assess total NMS burden in addition to classic motor symptom scoring. Recent data from newly diagnosed PD patients also suggests there are different subtypes of PD that may have implications for both clinical trial design and the selection of therapy. Cognitive impairment often occurs in patients with PD, even in early disease, progressing to PD dementia in a substantial proportion of patients, which can limit therapeutic options. Posterior cortical dysfunction is a negative predictor of the progression of PD with mild cognitive impairment to PD dementia. Pronounced nigrostriatal denervation is characteristic of PD; however, cholinergic changes are also observed. Cholinergic depletion starts early in the disease process and by the time PD dementia develops patients will have a significant cholinergic deficit in various cortical regions.Current research is focused on the potential to reduce cognitive decline by decreasing beta-amyloid plaques. KeywordsParkinson's disease (PD), non-motor symptoms, dopamine, cognitive impairment, apomorphine Disclosure: Amos D Korczyn has received honoraria for sponsored symposia in educational meetings from Britannia. K Ray Chaudhuri has received honoraria for sponsored symposia in educational meetings from AbbVie, Britannia, Mundipharma, Otsuka, UCB and US WorldMeds. He has received educational grants from AbbVie, Britannia, Medtronic and UCB. Teus van Laar has received honoraria for sponsored symposia in educational meetings from AbbVie, Britannia, UCB and Medtronic.

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The Heterogeneity of Early Parkinson’s Disease: A Cluster Analysis on Newly Diagnosed Untreated Patients

Cited by 170 publications

References 43 publications

Non motor subtypes and Parkinson's disease

Non motor subtypes and Parkinson's disease

Can metabotyping help deliver the promise of personalised nutrition?

Extending our Understanding of the Dopaminergic Basis of Non-motor Symptoms in Parkinson’s Disease

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