Cited by 2,807Parkinson's Disease Mechanisms and TreatmentsDeep Brain Stimulation and Movement DisordersDementia and Cognitive Impairment Research

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Non-motor symptoms of Parkinson's disease: diagnosis and management

Chaudhuri, K Ray, Healy, Daniel G, Schapira, Anthony HV·2006·The Lancet Neurology

DOI 10.1016/s1474-4422(06)70373-8

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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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Treatment Options for Urogenital Dysfunction in Parkinson’s Disease
Batla, A., Tayim, N., Pakzad, M. H., & Panicker, J. N. (2016) · Current Treatment Options in Neurology · doi:10.1007/s11940-016-0427-0 · Cited by 37
Pattern of cognitive impairment in patients with Parkinson's disease and psychosis: A critical review
Lenka, A., Hegde, S., Arumugham, S. S., & Pal, P. K. (2016) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2016.12.025 · Cited by 36
The role of the retina in visual hallucinations: A review of the literature and implications for psychosis
Bernardin, F., Schwan, R., Lalanne, L., Ligier, F., Angioï-Duprez, K., Schwitzer, T., & Laprévote, V. (2017) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2017.03.002 · Cited by 36
“Pregeniculate visual dysfunctions and eye complications form part of the non-motor clinical picture in Parkinson disease (Chaudhuri et al., 2006).”
Striatal cholinergic interneurons regulate cognitive and affective dysfunction in partially dopamine‐depleted mice
Ztaou, S., Lhost, J., Watabe, I., Torromino, G., & Amalric, M. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14153 · Cited by 33
“discrimination, working memory, attention processes and flexibility which can be related to both striatal and prefrontal dysfunction (Chaudhuri et al., 2006; 2011; Owen et al., 1993).”
BackgroundInfluential
Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly
Estevez‐Fraga, C., Zeun, P., & López-Sendón, J. L. (2018) · Drugs & Aging · doi:10.1007/s40266-018-0590-y · Cited by 36
Inferring sleep stage from local field potentials recorded in the subthalamic nucleus of Parkinson's patients
Christensen, E., Abosch, A., Thompson, J. A., & Zylberberg, J. (2018) · Journal of Sleep Research · doi:10.1111/jsr.12806 · Cited by 35
“This would serve a crucial unmet need in this patient population (Chaudhuri et al., 2006), as there are currently no effective treatments with a low side‐effect burden (Arnulf et al., 2000).”
Background
Early-onset Parkinsonian behaviors in female Pink1-/- rats
Marquis, J. M., Lettenberger, S. E., & Kelm‐Nelson, C. A. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112175 · Cited by 34
REM Sleep Behavior Disorder in Parkinson’s Disease: Effects on Cognitive, Psychiatric, and Functional outcomes
Mahmood, Z., Patten, R. V., Nakhla, M. Z., Twamley, E. W., Filoteo, J. V., & Schiehser, D. M. (2020) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617720000430 · Cited by 36
Nonmotor symptoms in Parkin gene‐related parkinsonism
Kägi, G., Klein, C., Wood, N. W., Schneider, S. A., Pramstaller, P. P., Tadić, V., Quinn, N. P., van de Warrenburg, B. P. C., & Bhatia, K. P. (2010) · Movement Disorders · doi:10.1002/mds.22897 · Cited by 36
Anxiety‐provoked gait changes are selectively dopa‐responsive in Parkinson's disease
Martens, K. A. E., Ellard, C. G., & Almeida, Q. J. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.12928 · Cited by 36
“…may be an alternative therapeutic strategy, as dopamine agonists can increase dopamine levels within the limbic system (D3 receptors) and alleviate anxiety symptoms (Chaudhuri et al., 2006; Lemke, 2008; Coakeley et al., 2014), which might also reduce motor symptoms that are worsened by anxiety.”
Background
A short Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s Disease: first psychometric approach
Martínez‐Martín, P., Payo, B. F., Agüera-Ortíz, L., & Ayuga-Martinez, A. (2012) · Journal of Neurology · doi:10.1007/s00415-012-6490-x · Cited by 36
DJ-1 deficient mice demonstrate similar vulnerability to pathogenic Ala53Thr human -syn toxicity
Ramsey, C. P., Tsika, E., Ischiropoulos, H., & Giasson, B. I. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq017 · Cited by 37
“bradykinesia, postural instability, resting tremor and rigidity, which result from the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (12–16), as well as a range of non-motor symptoms (17,18).”
Background
A pilot randomized controlled trial of sleep therapy in Parkinson's disease: effect on patients and caregivers
Leroi, I., Baker, P., Kehoe, P., Daniel, E., & Byrne, E. J. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2472 · Cited by 36
“Sleep disturbances may be seen in up to 96% of PD patients (Chaudhuri et al., 2006) and have a significant negative impact on the quality of life of PD patients (Happe and Berber, 2001).”
Background
What is measured with verbal fluency tests in Parkinson’s disease patients at different stages of the disease?
Koerts, J., Meijer, H., Colman, K. S. F., Tucha, L., Lange, K. W., & Tucha, O. M. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-012-0885-9 · Cited by 36
“Cognitive impairments are present in both late and early stages of Parkinson’s disease (PD) (Chaudhuri et al. 2006) and have been observed in the domains of executive functioning, memory, and psychomotor speed (Aarsland et al. 2010; Koerts et al. 2011).”
Decreased sleep quality in Parkinson’s patients is associated with higher anxiety and depression prevalence and severity, and correlates with pain intensity and quality
Rana, A. Q., Qureshi, A. R., Oghli, Y. S., Saqib, Y., Mohammed, B. I., Sarfraz, Z., & Rana, R. (2018) · Neurological Research · doi:10.1080/01616412.2018.1462880 · Cited by 36
Functional Neuroanatomy and Behavioural Correlates of the Basal Ganglia: Evidence from Lesion Studies
Ward, P., Seri, S., & Cavanna, A. E. (2013) · Behavioural Neurology · doi:10.1155/2013/616741 · Cited by 36
Interactions between interoception and perspective-taking: Current state of research and future directions
Baiano, C., Job, X., Santangelo, G., Auvray, M., & Kirsch, L. P. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.08.007 · Cited by 38
“Parkinson’s disease is characterized by a large spectrum of non-motor symptoms ranging from cognitive to behavioural disturbances (Chaudhuri et al., 2006).”
Role of Ceramides and Sphingolipids in Parkinson's Disease
Vos, M. H., Klein, C., & Hicks, A. A. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168000 · Cited by 37
A controlled trial of an educational programme for people with Parkinson's disease
Lindskov, S., Westergren, A., & Hagell, P. (2007) · Journal of Clinical Nursing · doi:10.1111/j.1365-2702.2007.02076.x · Cited by 35
Clinical heterogeneity in patients with early-stage Parkinson’s disease: a cluster analysis
Liu, P., Feng, T., Wang, Y., Zhang, X., & Chen, B. (2011) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1100069 · Cited by 35
“…such as rapid-eye movement sleep behavior disorder, constipation, and depression have been strongly suggested as preclinical (motor) characteristics in PD, while restless legs syndrome, apathy, fatigue, and anxiety have also been suggested to have links with early-stage PD (Chaudhuri et al., 2006).”
Background
Metabotropic glutamate receptor 4 (mGlu4)-positive allosteric modulators for the treatment of Parkinson's disease: historical perspective and review of the patent literature
Lindsley, C. W., & Hopkins, C. R. (2012) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2012.679437 · Cited by 35
“First described by James Parkinson in 1817, as “shaking palsy” or “paralysis agitans,” the disease that now bears his name is characterized by five classic symptoms: bradykinesia (slowness of movement), tremor, rigidity, postural changes, and gait disorders [1-5].”
BackgroundInfluential
Dopamine signals and physiological origin of cognitive dysfunction in Parkinson's disease
Matsumoto, M. (2015) · Movement Disorders · doi:10.1002/mds.26177 · Cited by 37
Knowledge of Parkinson’s Disease in a Multiethnic Urban Asian Setting
Tan, A. H., Tan, C. T., Marras, C., Loh, K. W., Wye, N. H. W., Lim, Q. H., Tan, P. W., Lim, C. C., Cheong, Y. W., Kong, S. T., et al. (2015) · Journal of Parkinson s Disease · doi:10.3233/jpd-150594 · Cited by 35
An fMRI study into emotional processing in Parkinson’s disease: Does increased medial prefrontal activation compensate for striatal dysfunction?
Moonen, A. J. H., Weiss, P. H., Wiesing, M., Weidner, R., Fink, G. R., Reijnders, J. S. A. M., Weber, W. E. J., & Leentjens, A. F. G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177085 · Cited by 39
Understanding and Treating Pain Syndromes in Parkinson's Disease
Gandolfi, M., Geroin, C., Antonini, A., Smania, N., & Tinazzi, M. (2017) · International review of neurobiology · doi:10.1016/bs.irn.2017.05.013 · Cited by 34
Phosphorylated α-synuclein deposits in sural nerve deriving from Schwann cells: A biomarker for Parkinson's disease
Zhang, H., Zhu, L., Sun, L., Zhi, Y., Ding, J., Yuan, Y., Shen, F., Li, X., Ji, P., Wang, Z., et al. (2018) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2018.10.003 · Cited by 35
Impairments in face discrimination and emotion recognition are related to aging and cognitive dysfunctions in Parkinson’s disease with dementia
Ho, M. W.-R., Chien, S. H., Lu, M., Chen, J., Aoh, Y., Chen, C., Lane, H., & Tsai, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-61310-w · Cited by 36
The Non-Motor Symptom Profile of Progressive Supranuclear Palsy
Chaithra, S. P., Prasad, S., Holla, V. V., Stezin, A., Kamble, N. L., Yadav, R., & Pal, P. K. (2020) · Journal of Movement Disorders · doi:10.14802/jmd.19066 · Cited by 35
Serum Uric Acid Levels and Non-Motor Symptoms in Parkinson’s Disease
van Wamelen, D. J., Taddei, R. N., Calvano, A., Titova, N., Leta, V., Shtuchny, I. V., Jenner, P. G., Martínez‐Martín, P., Катунина, Е. А., & Chaudhuri, К. R. (2020) · Journal of Parkinson s Disease · doi:10.3233/jpd-201988 · Cited by 35
“The range of NMS that occurs in PD is broad [15] and theoverallburdenofNMSimpactsadverselyonqual-ityoflife(QoL)inPD[16].”
Where Dopaminergic and Cholinergic Systems Interact: A Gateway for Tuning Neurodegenerative Disorders
Amalric, M., Pattij, T., Sotiropoulos, I., Silva, J. M., Sousa, N., Ztaou, S., Chiamulera, C., Wahlberg, L. U., Emerich, D. F., & Paolone, G. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.661973 · Cited by 35
Phytocannabinoids and Cannabis-Based Products as Alternative Pharmacotherapy in Neurodegenerative Diseases: From Hypothesis to Clinical Practice
Paes-Colli, Y., Aguiar, A. F. L., Isaac, A. R., Ferreira, B. K., Campos, R. M. P., Trindade, P. M. P., Reis, R. A. D. M., & Sampaio, L. D. S. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.917164 · Cited by 39
Mesocortical dopamine system modulates mechanical nociceptive responses recorded in the rat prefrontal cortex
Sogabe, S., Yagasaki, Y., Onozawa, K., & Kawakami, Y. (2013) · BMC Neuroscience · doi:10.1186/1471-2202-14-65 · Cited by 35
“In clinical reports on PD, patients frequently complain of neuropathic or central pain before motor disorders [12-14].”
Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats
MATHEUS, F. C., Rial, D., Real, J. I., Lemos, C., Ben, J., Guaita, G. O., Pita, I. R., Sequeira, A., Pereira, F. C., Walz, R., et al. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.12.011 · Cited by 35
Dopamine agonists in Parkinson’s disease
Yamamoto, M., & Schapira, A. H. V. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.4.671 · Cited by 35
Self-citation
Comparison of Associations between MIND and Mediterranean Diet Scores with Patient-Reported Outcomes in Parkinson’s Disease
Fox, D. J., Park, S. J., & Mischley, L. K. (2022) · Nutrients · doi:10.3390/nu14235185 · Cited by 34
“Recent studies have focused on NMS for the prediction and diagnosis of PD [3,5,6] because prodromal PD (pPD) is difficult identify and manage without subjective or patient-reported outcome (PRO) measures [1].”
Background
Non-motor symptoms in a Flanders-Belgian population of 215 Parkinson's disease patients as assessed by the Non-Motor Symptoms Questionnaire.
Crosiers, D., Pickut, B. A., Theuns, J., Deyn, P. P. D., Broeckhoven, C. V., Martínez‐Martín, P., Chaudhuri, К. R., & Cras, P. P. (2012) · Europe PMC (PubMed Central) · Cited by 34
Delusional misidentification syndrome and other unusual delusions in advanced Parkinson's disease
Moro, A., Munhoz, R. P., Moscovich, M., Arruda, W. O., & Teive, H. A. G. (2013) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2013.04.021 · Cited by 34
“However, this group of patients usually present with disabling non-motor symptoms, including cognitive impairment (dysexecutive syndrome, subcortical and frontal dementia), dysautonomia (postural hypotension, urinary dysfunction, constipation, sexual dysfunction, pain), sleep disorders, depression, anxiety, and psycho…”
Background

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)
DOI: 10.1016/s1474-4422(06)70373-8
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Non-motor symptoms of Parkinson's disease: diagnosis and management

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