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Non-motor symptoms of Parkinson's disease: diagnosis and management
Abstract
The clinical diagnosis of Parkinson's disease rests on the identification of the characteristics related to dopamine deficiency that are a consequence of degeneration of the substantia nigra pars compacta. However, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably emerge with disease progression. Indeed, non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy. By contrast with the dopaminergic symptoms of the disease, for which treatment is available, non-motor symptoms are often poorly recognised and inadequately treated. However, attention is now being focused on the recognition and quantitation of non-motor symptoms, which will form the basis of improved treatments. Some non-motor symptoms, including depression, constipation, pain, genitourinary problems, and sleep disorders, can be improved with available treatments. Other non-motor symptoms can be more refractory and need the introduction of novel non-dopaminergic drugs. Inevitably, the development of treatments that can slow or prevent the progression of Parkinson's disease and its multicentric neurodegeneration provides the best hope of curing non-motor symptoms.
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“Indeed, non-motor symptoms dominate the clinical picture of PD”
From Distant delivery of a mindfulness-based intervention for people with Parkinson's disease: The study protocol of a randomised pilot trial (2017) · cites this paper as [2]
In the citing paper
“and contribute to severe disability, impaired quality of life, and shortened life expectancy [2].”
From Distant delivery of a mindfulness-based intervention for people with Parkinson's disease: The study protocol of a randomised pilot trial (2017) · cites this paper as [2]
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“Interestingly, constipation does not respond well to dopamine therapy (Chaudhuri et al., 2006) and its onset may precede motor impairments (Abbott et al., 2001).”
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Ruiz, P., Catalán, M. J., & Carril, J. M. F. (2011) · The Neurologist · doi:10.1097/nrl.0b013e31823966b4 · Cited by 32
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BackgroundUnraveling a new circuitry for sleep regulation in Parkinson's disease
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Campos, A. C. P., Berzuino, M. B., Hernandes, M. S., Fonoff, E. T., & Pagano, R. L. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.04.015 · Cited by 36
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“In addition, non-motor symptoms, including olfactory deficits, anxiety, and cognitive impairment, also occur in patients with PD, sometimes appearing before the onset of motor dysfunction [2,3].”
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Subthalamic deep brain stimulation improves sleep and excessive sweating in Parkinson’s disease
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“In addition, they merely aim to augment DA transmission and so would not resolve issues arising directly from a deficit in noradrenergic and serotonergic transmission (Chaudhuri et al., 2006).”
RetractedExamining Braak's hypothesis by imaging Parkinson's disease
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Emotion in action: When emotions meet motor circuits
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“Therefore, from the point of view of improving the patient’s QOL, it is essential to give careful attention to the treatment of psychiatric symptoms as well as the motor symptoms.”
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“Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by a wide clinical spectrum of motor and nonmotor symptoms causing progressive disability at the later stages of the disease [1].”
BackgroundCirculating Exosome microRNAs as Diagnostic Biomarkers of Dementia
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Current and emerging therapeutic targets for Parkinson’s disease
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Parkinson's disease and mitochondrial gene variations: A review
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“addition to the limitation of movement, patients afflicted with PD may suffer from mild to severe neuropsychiatric disturbances, including disorders of speech and swallowing [10], mood [11], sleep [12], cognition [13], behavior and thought [5].”
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Implicit and explicit processing of emotional facial expressions in Parkinson’s disease
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Patient's Loss of Empathy Is Associated With Caregiver Burden
Pomponi, M., Ricciardi, L., Torre, G. L., Fusco, D., Morabito, B., Ricciardi, D., Gioia, A. D., Bernabei, R., & Bentivoglio, A. R. (2016) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0000000000000568 · Cited by 30
“…of psychiatric disorders (including depression, anxiety, apathy, hallucinations, and impulse control disorders) and other nonmotor symptoms (NMSs) (Chaudhuri et al., 2006) dramatically increases; yet, they are often underrecognized in clinical practice, because of the lack of complaints referred…”
BackgroundNonmotor Symptoms in Experimental Models of Parkinson's Disease
Titova, N., Schapira, A. H. V., Chaudhuri, К. R., Qamar, M. A., Катунина, Е. А., & Jenner, P. G. (2017) · International review of neurobiology · doi:10.1016/bs.irn.2017.05.018 · Cited by 30
Self-citationZhu, J., Wang, S., Liang, Y., & Xu, X. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.07.023 · Cited by 30
Vos, M. H., & Klein, C. (2021) · Cells · doi:10.3390/cells10030579 · Cited by 32
“The origin of the non-motor symptoms is poorly understood, and non-motor symptoms that pose a strong burden on the quality of life are dementia and sleep problems with the accompanying deregulation of the circadian rhythm [5,7,8].”
BackgroundFuture directions in the treatment of Parkinson's disease
Schapira, A. H. V. (2007) · Movement Disorders · doi:10.1002/mds.21679 · Cited by 30
Self-citationGray, W. K., Hildreth, A. J., Bilclough, J. A., Wood, B. H., Baker, K., & Walker, R. W. (2009) · Movement Disorders · doi:10.1002/mds.22610 · Cited by 30
“important predictors of disease progression and mortality in PD, as noted by other authors.(6,8,34,35) Tinetti gait score, age, and sex appear to be inde-”
ResultAlbares, M., Thobois, S., Favre, É., Broussolle, E., Polo, G., Domenech, P., Boulinguez, P., & Ballanger, B. (2014) · Brain stimulation · doi:10.1016/j.brs.2014.09.002 · Cited by 34
Bee venom for the treatment of Parkinson’s disease: How far is it possible?
Awad, K., Abushouk, A. I., Abdelkarim, A., Mohammed, M., Negida, A., & Shalash, A. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.04.065 · Cited by 30
Mukhtar, S. M., Imran, R., Zaheer, M., & Tariq, H. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-019172 · Cited by 30
The PRIAMO study: background, methods and recruitment
Antonini, A., Colosimo, C., Marconi, R., Morgante, L., & Barone, P. (2008) · Neurological Sciences · doi:10.1007/s10072-008-0863-z · Cited by 30
Non-Motor Off Symptoms in Parkinson's Disease
Cheon, S., Park, M., Kim, W.-J., & Kim, J. W. (2009) · Journal of Korean Medical Science · doi:10.3346/jkms.2009.24.2.311 · Cited by 30
“These include neuropsychiatric symptoms, sleep disturbance, dysautonomia and sensory symptoms, and have a great impact on the quality of life for PD patients (2).”
BackgroundFifel, K., Piggins, H., & Deboer, T. (2016) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2015.02.005 · Cited by 30
Impact of non-motor fluctuations on QOL in patients with Parkinson’s disease
Kakimoto, A., Kawazoe, M., Kurihara, K., Mishima, T., & Tsuboi, Y. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1149615 · Cited by 29
Anti-oxidative activity of probiotics; focused on cardiovascular disease, cancer, aging, and obesity
Kavyani, B., Ahmadi, S., Nabizadeh, E., & Abdi, M. (2024) · Microbial Pathogenesis · doi:10.1016/j.micpath.2024.107001 · Cited by 31
Komadina, N. C., Terpening, Z., Huang, Y. M., Halliday, G. M., Naismith, S. L., & Lewis, S. J. G. (2011) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000328165 · Cited by 30
“Parkinson’s disease (PD) is a progressive neurodegenerative disorder, typically characterized by its motor features (bradykinesia, tremor, rigidity and postural instability). However, it has become increasingly apparent that non-motor features – such as dementia, mood disorders, psychosis and autonomic dysfunction – a…”
BackgroundSynaptic Protein Alterations in Parkinson’s Disease
Pienaar, I. S., Burn, D. J., Morris, C. M., & Dexter, D. T. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8226-9 · Cited by 28
Preservation of function in Parkinson's disease: What's learning got to do with it?
Beeler, J. A. (2011) · Brain Research · doi:10.1016/j.brainres.2011.09.040 · Cited by 29
“…the traditional viewof dopamine cell loss and impaired motor control (Aarsland et al., 2010; Bosboom et al., 2004; Chaudhuri and Schapira, 2009; Chaudhuri et al., 2006; Frank, 2005; Jankovic, 2008; Levin and Katzen, 2005; Owen et al., 1992;Wiecki and Frank, 2010; Zgaljardic et al., 2004)…”
BackgroundA clinical overview of non-motor symptoms in Parkinson's Disease.
Modugno, N., Lena, F., Biasio, F. D., Cerrone, G., Ruggieri, S. A., & Fornai, F. (2013) · PubMed · Cited by 27
Effect and Mechanism of Chinese Herbal Medicine on Parkinson's Disease
Zeng, B. (2017) · International review of neurobiology · doi:10.1016/bs.irn.2017.02.004 · Cited by 29
Neonatal AAV delivery of alpha-synuclein induces pathology in the adult mouse brain
Delenclos, M., Faroqi, A. H., Yue, M., Kurti, A., Castanedes‐Casey, M., Rousseau, L., Phillips, V. R., Dickson, D. W., Fryer, J. D., & McLean, P. J. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0455-3 · Cited by 29
membership, C., Rudyk, C., Dwyer, Z., & Hayley, S. P. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1483-7 · Cited by 29
The role of Optical Coherence Tomography in Parkinsonism: A critical review
Mailankody, P., Lenka, A., & Pal, P. K. (2019) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2019.06.009 · Cited by 31
Etiologies of insomnia in Parkinson's disease – Lessons from human studies and animal models
Mizrahi-Kliger, A. D., Feldmann, L. K., Kühn, A. A., & Bergman, H. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.113976 · Cited by 32
“ameliorating effect through decreasing motor symptoms, and an aggravating effect through increasing hallucinations (Chaudhuri et al., 2006) or nocturia (Uchiyama et al.”
Pfeiffer, R. F. (2007) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(08)70004-x · Cited by 29
“disability, and a significant economic burden [2].”
Pramipexole Extended-Release: A Review of Its Use in Patients with Parkinson’s Disease
Frampton, J. E. (2014) · Drugs · doi:10.1007/s40265-014-0322-5 · Cited by 29
“sleep disturbances, mood and behavioural disorders, cognitive and autonomic dysfunction) are highly prevalent, and also contribute to severe disability, impaired quality of life and shortened life expectancy [1, 2].”
BackgroundTillman, A., Muthalib, M., Hendy, A. M., Johnson, L. G., Rantalainen, T., Kidgell, D. J., Enticott, P. G., & Teo, W. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00040 · Cited by 30
“In addition to motor deficits, people with PD often experience non-motor impairments such as cognitive, neuropsychiatric, sleep, autonomic and sensory disturbances that results in a reduced quality-of-life (Chaudhuri et al., 2006; Park and Stacy, 2009).”
BackgroundMild cognitive impairment in Parkinson's disease versus Alzheimer's disease
Besser, L. M., Litvan, I., Monsell, S. E., Mock, C., Weıntraub, S., Zhou, X., & Kukull, W. A. (2016) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2016.04.007 · Cited by 33
Increase of Reproductive Life Span Delays Age of Onset of Parkinson’s Disease
Frentzel, D., Judanin, G., Borozdina, O., Klucken, J., Winkler, J., & Schlachetzki, J. C. M. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00397 · Cited by 29
Hadinia, A., Meyer, A., Bruegger, V., Hatz, F., Nowak, K., Taub, E., Nyberg, E., Stieglitz, R.-D., Fuhr, P., & Gschwandtner, U. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2016.01975 · Cited by 20
“…del Sacro Cuore, Italy Reviewed by: Maria Luisa Rusconi, University of Bergamo, Italy Michelle Dow Keawphalouk, Harvard University and Massachusetts Institute of Technology (MIT), USA *Correspondence: Anousha Hadinia anousha.hadinia@unibas.ch Specialty section: This article was submitted to…”
BackgroundInfluentialGuo, X., Tang, P., Hou, C., Chong, L., Zhang, X., Liu, P., Chen, L., Liu, Y., Zhang, L., & Li, R. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.875101 · Cited by 19
Metadata
- Authors
- Chaudhuri, K. R., Healy, D. G., & Schapira, A. H.
- Affiliations
- Guy's and St Thomas' NHS Foundation Trust (GB)
- The Royal Free Hospital (GB)
- ORCID
- Schapira, Anthony HV
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 5
- Issue
- 3
- Pages
- 235-245
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W1982535961
- Cited by
- 2,807
- References
- 140
- Citations by year
- 2026: 184 · 2025: 170 · 2024: 143 · 2023: 159 · 2022: 168 · 2021: 165 · 2020: 197 · 2019: 168 · 2018: 161 · 2017: 174 · 2016: 152 · 2015: 156 · 2014: 130 · 2013: 130 · 2012: 129
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Parkinson's disease, non-motor symptoms, depression, constipation, pain, genitourinary dysfunction, sleep disorders, substantia nigra pars compacta, neurodegeneration, quality of life, disability
- MeSH terms
- Autonomic Nervous System Diseases, Humans, Pain, Parkinson Disease, Psychotic Disorders, Sleep Wake Disorders, Disease Progression, Pain Management
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