The review was based on information obtained from papers identified by searches of PubMed and Google with the terms “non motor”, “Parkinson's disease”, and “cognitive” as the main keywords, between 1960 and September 2005. Information was also obtained from perusal of abstract supplements of the Movement Disorders journal based on international congress proceedings. Articles were cited on the basis of importance in relation to non-motor aspects of Parkinson's disease, ease of access, and
ReviewNon-motor symptoms of Parkinson's disease: diagnosis and management
Introduction
James Parkinson1 accurately described the motor problems of patients but also noted several non-motor features. The motor disorder of Parkinson's disease has been extensively researched resulting in improved diagnostic accuracy and development of robust rating scales and treatment startegies.2, 3 Despite this emphasis on motor symptomatology, several studies have shown that the non-motor symptoms of Parkinson's disease, such as depression, psychosis, falls, and sleep disturbance, have greater significance when assessed by quality-of-life measures, institutionalisation rates, or health economics.4, 5, 6, 7, 8, 9, 10, 11
Section snippets
The scale of the problem
Non-motor symptoms correlate with advancing age and disease severity, although some non-motor symptoms, such as olfactory problems, constipation, depression, and rapid eye movement disorder, can occur early in the disease (panel 1).12 As the average age and life expectancy of the population increases, the non-motor features of Parkinson's disease become increasingly important.12, 13 The prevalence of non-motor symptoms as a whole is inadequately documented because there are insufficient
Pathophysiology of the non-motor symptom complex and the Braak hypothesis
Our understanding of the sequence and distribution of pathological changes in Parkinson's disease continues to evolve with non-dopaminergic-cell dysfunction being thought to play a major part in the development of the non-motor symptom complex.15, 16 The neuroanatomical and neurochemical substrates for much of the non-motor symptom complex in Parkinson's disease are unknown. A substantial part of the discussion in relation to pathophysiology of non-motor symptoms, therefore, remains
Nocturnal non-motor symptoms
Virtually all patients with Parkinson's disease have sleep disruption and studies show that this usually starts early in the disease course.27, 28 The causes of sleep disturbance are multifactorial, but pathological degeneration of central sleep regulation centres in the brainstem and thalamocortical pathways is probably important. The pedunculopontine nucleus, the locus coeruleus, and the retrorubral nucleus affect normal REM atonia and phasic generator circuitry and, as discussed previously,
Recognition of non-motor symptoms
The non-motor-symptom complex of Parkinson's disease is frequently overlooked. In a prospective study of 101 patients, neurologists did not discuss important symptoms such as depression, anxiety, fatigue, and sleep disturbance with more than 50% of their patients.115 This finding could be a result of limited consultation time, perception of the patient and the carer that their symptoms are unrelated to the disease (eg, visual hallucinations or diplopia), or non-awareness of the physician who
Non-motor rating scales
Panel 3 lists some of the existing non-motor scales in Parkinson's disease. Most scales address individual non-motor symptoms such as sleep, excessive daytime sleepiness, dysautonomia, fatigue, psychosocial aspects and depression, and quality of life.116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135 An integrated instrument that addresses the whole and diverse range of non-motor symptoms is not available to date, although some are in preparation
Burden of non-motor symptoms
Parkinson's disease decreases quality of life for patients and imposes a significant economic burden on society comparable with other chronic diseases, such as congestive heart failure, diabetes, and stroke.136, 137 The health economics in relation to hospital versus community-based management of non-motor symptoms is poorly evaluated, although individual symptoms such as visual hallucinations, dementia, and falls are a major source of hospitalisation and institutionalisation. A UK based cost
Is there a role for dopaminergic treatment?
A comprehensive description of the treatment strategies for the non-motor symptom complex of Parkinson's disease is beyond the scope of this review and we recommend a series of recent excellent reviews that focus on individual non-motor symptoms of the disease.28, 46, 48, 79, 86, 105 However, the evidence base for treatment of the non-motor symptom complex is poor and a review of the pharmacological and surgical treatments of the disease by the Movement Disorders Society Task Force highlighted
Conclusion
Early recognition of non-motor symptoms is essential for the care of patients with Parkinson's disease and the importance of a multidisciplinary approach, including support for carers, cannot be overemphasised.5 Poor recognition of non-motor symptoms affects cost of care of patients with the disease in society; the development of integrated methods to measure non-motor symptoms will help identification and the development of better treatment strategies in the future.
Search strategy and selection criteria
References (141)
- et al.
The sleep switch: hypothalamic control of sleep and wakefulness
Trends Neurosci
(2001) - et al.
Functional anatomy of the basal ganglia 1: the cortico-basal ganglia-thalamo-cortical loop
Brain Res Rev
(1995) - et al.
Parkinson's disease and sleep
Sleep Med Rev
(2003) - et al.
Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep
Brain Res
(1992) - et al.
Sleep attacks in Parkinson's disease
Lancet
(2000) - et al.
Neurobehavioural mechanism of reward and motivation
Curr Opin Neurobiol
(1996) - et al.
Negative symptoms: the ‘pathology’ of motivation and goal-directed behaviour
Trends Neurosci
(2000) Dementia associated with Parkinson's disease
Lancet Neurol
(2003)Gastrointestinal dysfunction in Parkinson's disease
Lancet Neurol
(2003)- et al.
Growth hormone response to clonidine in central and peripheral autonomic failure
Lancet
(1992)
Dimensions of sexual dysfunction in Parkinson Disease
Am J Geriatr Psychiatry
An essay on the shaking palsy [reprint of monograph published by Sherwood, Neely, and Jones, London, 1817]
J Neuropsychiatry Clin Neurosci
Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases
J Neurol Neurosurg Psychiatry
Unified Parkinson's disease rating scale
Factors impacting on quality of life in Parkinson's disease: results from an international survey
Mov Disord
The holistic management of Parkinson's using a novel non-motor symptom scale and questionnaire
Adv Clin Neurosci Rehab
Predictors of nursing home placement in Parkinson's disease: a population-based, prospective study
J Am Geriatr Soc
Nonmotor fluctuations in Parkinson's disease: frequent and disabling
Neurology
What contributes to quality of life in patients with Parkinson's disease?
J Neurol Neurosurg Psychiatry
Direct economic impact of Parkinson's disease: a research survey in the United Kingdom
Mov Disord
Resource use and costs in a Swedish cohort of patients with Parkinson's disease
Mov Disord
The impact of comorbid disease and injuries on resource use and expenditures in parkinsonism
Neurology
The non-motor symptom complex of Parkinson's disease: time for a comprehensive assessment
Curr Neurol Neurosci Rep
Sydney multicenter study of Parkinson's disease: non-L-dopa-responsive problems dominate at 15 years
Mov Disord
A clinical observational study of the pattern and occurrence of non-motor symptoms in Parkinson's disease ranging from early to advanced disease
Mov Disord
Challenging conventional wisdom: the etiologic role of dopamine oxidative stress in Parkinson's disease
Mov Disord
Central neurotransmitters and neuromodulators in cardiovascular regulation
Staging of brain pathology related to sporadic Parkinson's disease
Neurobiol Aging
Idiopathic Parkinson's disease: staging an α-synucleinopathy with a predictable pathoanatomy
Emerging views of dopamine in modulating sleep/wake state from an unlikely source: PD
Neurology
Repeated visual hallucinations in Parkinson's disease as disturbed external/internal perceptions: focused review and a new integrative model
Mov Disord
Idiopathic REM sleep behavior disorder: toward a better nosologic definition
Neurology
The two faces of eve: dopamine's modulation of wakefulness and sleep
Neurology
Cognitive status correlates with neuropathologic stage in Parkinson disease
Neurology
The pallidosubthalamic projection: an anatomical substrate for non motor functions of the subthalamic nucleus in primates
Mov Disord
Nocturnal symptom complex in PD and its management
Neurology
Muscle tone suppression and stepping produced by stimulation of midbrain and rostral pontine reticular formation
J Neurosci
Parkinson's disease and sleepiness: an integral part of PD
Neurology
Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder
Neurology
Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases
Brain
REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease
Neurology
Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder: comparison with Parkinson's disease and controls
Brain
Incidental Lewy body disease in patients with REM sleep behaviour disorder
Neurology
Combination of idiopathic REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT
Brain
Excessive daytime sleepiness and the future risk of Parkinson's disease
Mov Disord
Excessive daytime sleepiness in Parkinson's disease
Neurology
Why excessive daytime sleepiness is an important issue in Parkinson's disease
Adv Clin Neurol Rehab
Sudden daytime sleep onset in Parkinson's disease: polysomnographic recordings
Mov Disord
Polysomnographic characterisation of pergolide-induced sleep attacks in idiopathic PD
Neurology
Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole
Neurology
Cited by (2088)
Apnea behavior in early- and late-stage mouse models of Parkinson's disease: Cineradiographic analysis of spontaneous breathing, acute stress, and swallowing
2024, Respiratory Physiology and NeurobiologyThe impact of psychiatric comorbidity on Parkinson's disease outcomes: a systematic review and meta-analysis
2024, The Lancet Regional Health - EuropeDepressive Symptoms and the Subsequent Risk of Parkinson's Disease: A Nationwide Cohort Study
2024, American Journal of Geriatric PsychiatryTowards a biological diagnosis of PD
2024, Parkinsonism and Related DisordersDelivering the diagnosis of Parkinson's disease- setting the stage with hope and compassion
2024, Parkinsonism and Related DisordersNeuropathogenesis-on-chips for neurodegenerative diseases
2024, Nature Communications