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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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Association between Parkinson's Disease and Helicobacter Pylori
Çamcı, G., & Oğuz, S. (2016) · Journal of Clinical Neurology · doi:10.3988/jcn.2016.12.2.147 · Cited by 109
Potential Neuroprotective Activity of Ginseng in Parkinson’s Disease: A Review
González‐Burgos, E., Fernández‐Moriano, C., & Gómez-Serranillos, M. P. (2014) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-014-9569-6 · Cited by 108
Functional models of Parkinson's disease: A valuable tool in the development of novel therapies
Jenner, P. G. (2009) · Annals of Neurology · doi:10.1002/ana.21489 · Cited by 109
“Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alphasynuclein(1-120): implications for Lewy body disorders.”
BackgroundBrooks, D. J. (2008) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s1660 · Cited by 108
“In recent years there has been an increasing awareness of the importance of non-motor symptoms, such as mood and anxiety disorders, fatigue and apathy, cognitive impairments, sleep disorders and addictions (Chaudhuri et al 2006).”
Parkinson’s progression prediction using machine learning and serum cytokines
Rastegar, D. A., Ho, N., Halliday, G. M., & Dzamko, N. L. (2019) · npj Parkinson s Disease · doi:10.1038/s41531-019-0086-4 · Cited by 109
Sleep and circadian rhythms in Parkinson’s disease and preclinical models
Hunt, J., Coulson, E. J., Rajnarayanan, R. V., Oster, H., Videnović, A., & Rawashdeh, O. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00504-w · Cited by 118
“one of the most prominent non-motor symptoms of disease [273], it must be a key consideration of PD research.”
BackgroundNeurobiology of Depression and Anxiety in Parkinson's Disease
Kano, O., Ikeda, K., Cridebring, D., Takazawa, T., Yoshii, Y., & Iwasaki, Y. (2011) · Parkinson s Disease · doi:10.4061/2011/143547 · Cited by 107
Clinical prediction of Parkinson's disease: planning for the age of neuroprotection
Postuma, R. B., Gagnon, J., & Montplaisir, J. Y. (2010) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.174748 · Cited by 106
“Other sleep disorders Patients with PD have many other sleep manifestations, including insomnia and excessive daytime somnolence.(25) These abnormalities are due to degeneration in diffuse structures, which include pontine structures that degenerate in Stage 2 disease.”
BackgroundmTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders
Ryskalin, L., Limanaqi, F., Frati, A., Busceti, C. L., & Fornai, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082226 · Cited by 110
Lopatina, O. L., Yoshihara, T., Nishimura, T., Zhong, J., Akther, S., Fakhrul, A. A. K. M., Liang, M., Higashida, C., Sumi, K., Furuhara, K., et al. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00133 · Cited by 109
“…the appearance of nonmotor symptoms (Tessitore et al., 2002; Hälbig et al., 2011), such as anxiety, depression, olfactory and memory impairment, sleep abnormalities and gastrointestinal disturbances (Menza et al., 1993; Chaudhuri et al., 2006; Reijnders et al., 2008; Chaudhuri and Schapira, 2009).”
BackgroundCrizzle, A. M., Classen, S., & Uc, E. Y. (2012) · Neurology · doi:10.1212/wnl.0b013e3182749e95 · Cited by 105
Rascol, O., Zesiewicz, T., Chaudhuri, К. R., Asgharnejad, M., Surmann, E., Dohin, E., Nilius, S. M., & Bauer, L. (2015) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.678 · Cited by 105
Locus coeruleus-norepinephrine: basic functions and insights into Parkinson’s disease
Bari, B. A., Chokshi, V. B., & Schmidt, K. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.270297 · Cited by 112
“Almost all PD patients suffer from sleep disturbances with individual variability, which include disordered breathing, vivid dreaming and excessive daytime sleepiness (Chaudhuri et al., 2006; Verbaan et al., 2008).”
BackgroundΓιαννακοπούλου, Κ.-Μ., Roussaki, I. G., & Demestichas, K. P. (2022) · Sensors · doi:10.3390/s22051799 · Cited by 115
“However, clinical diagnosis is performed based on the latter, including the presence of bradykinesia, tremor or rigidity [5], as the former are often not easily detected and are usually attributed to other health factors and to senescence.”
BackgroundPoletti, M., & Bonuccelli, U. (2012) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125312470130 · Cited by 106
“com 101 Introduction Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor (bradykinesia, rigidity and resting tremors) and nonmotor symptoms (cognitive impairment, affective and behavioral disturbances, impairment of the autonomic nervous system) [Chaudhury et al. 2006].”
BackgroundThe prevalence and incidence of Parkinson’s disease in China: a systematic review and meta-analysis
Chun-lin, M., Su, L., Xie, J., Long, J., Wu, P., & Gu, L. (2013) · Journal of Neural Transmission · doi:10.1007/s00702-013-1092-z · Cited by 104
“Thus, higher mortality rates and lower life expectancies are seen in PD patients relative to the general population (Chaudhuri et al. 2006; Leibson et al. 2006; Poewe 2006).”
Shustak, S., Inzelberg, L., Steinberg, S., Rand, D., David‐Pur, M., Hillel, I., Katzav, S., Fahoum, F., Vos, M. D., Mirelman, A., et al. (2018) · Journal of Neural Engineering · doi:10.1088/1741-2552/aafa05 · Cited by 103
Assessing the non‐motor symptoms of Parkinson's disease: MDS ‐ UPDRS and NMS Scale
Martínez‐Martín, P., Chaudhuri, К. R., Rojo-Abuín, J. M., Rodríguez‐Blázquez, C., Álvarez, M., Arakaki, T., Bergareche‐Yarza, A., Chade, A. R., Garretto, N., Gershanik, O. S., et al. (2013) · European Journal of Neurology · doi:10.1111/ene.12165 · Cited by 103
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Zoccolella, S., Savarese, M., Lamberti, P., Manni, R., Pacchetti, C., & Logroscino, G. (2010) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2010.02.004 · Cited by 101
Martínez‐Martín, P., Macaulay, D. S., Jalundhwala, Y. J., Mu, F., Ohashi, E., Marshall, T., & Sail, K. (2018) · Movement Disorders · doi:10.1002/mds.27579 · Cited by 102
Visual Hallucinations in PD and Lewy Body Dementias: Old and New Hypotheses
ONOFRJ, M. C., Taylor, J., Monaco, D., Franciotti, R., Anzellotti, F., Bonanni, L., Onofrj, V., & Thomas, A. (2013) · Behavioural Neurology · doi:10.1155/2013/703924 · Cited by 103
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Alterations of mean diffusivity in brain white matter and deep gray matter in Parkinson's disease
Kim, H. J., Kim, S. J., Kim, H. S., Choi, C. G., Kim, N., Han, S., Jang, E. H., Chung, S. J., & Lee, C. S. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.06.050 · Cited by 101
Behavioural disorders, disability and quality of life in Parkinson's disease
Leroi, I., Ahearn, D., Andrews, M., McDonald, K. R., Byrne, E. J., & Burns, A. S. (2011) · Age and Ageing · doi:10.1093/ageing/afr078 · Cited by 105
“It is now accepted that in Parkinson’s disease (PD), a neurodegenerative motor disorder, non-motor features (including autonomic symptoms, sleep and sensory disturbances) are almost ubiquitous and often pre-date the motor features of the disorder [1].”
BackgroundJin, X., Wang, L., Liu, S., Zhu, L., Loprinzi, P. D., & Fan, X. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17010031 · Cited by 113
“With the degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies as pathological features [2], patients have gait and posture disorders, resting tremor, bradykinesia, muscle stiffness, and other characteristic motor symptoms [3]; accompanied by non-motor disorders such as sleep di…”
BackgroundJenner, P. G., Morris, H. R., Robbins, T. W., Goedert, M., Hardy, J., Ben‐Shlomo, Y., Bolam, J. P., Burn, D. J., Hindle, J. V., Brooks, D. J., et al. (2013) · Journal of Parkinson s Disease · doi:10.3233/jpd-130175 · Cited by 103
“These may precede or follow the occurrence of motor symptomatology and from a central nervous system perspective take PD in to the domain of a neuropsy-chiatric disorder with anxiety, depression and cognitive change as key components of the syndrome [4].”
Gender differences in non-motor symptoms in early, drug naïve Parkinson’s disease
Picillo, M., Amboni, M., Erro, R., Longo, K., Vitale, C., Moccia, M., Pierro, A., Santangelo, G., Rosa, A. D., Michele, G., et al. (2013) · Journal of Neurology · doi:10.1007/s00415-013-7085-x · Cited by 105
Parkinson disease patients' perspectives on palliative care needs
Boersma, I. M., Jones, J., Carter, J., Bekelman, D. B., Miyasaki, J. M., Kutner, J. S., & Kluger, B. M. (2016) · Neurology Clinical Practice · doi:10.1212/cpj.0000000000000233 · Cited by 100
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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