Abstract
Non-motor symptoms are very important for a better quality of life in patients with Parkinson’s disease (PD) but are not enough recognized and treated. The most common non-motor symptoms are pain, autonomic dysfunction, cognitive problems and dementia, depression, fatigue, apathy, sleep disturbances. Some of them precede motor symptoms and can be, also, very important in trying to recognize PD in an early phase. It appears that they are a major cause of disability. In this review the most often non-motor symptoms will be shown, especially cognitive problems and neuropsychiatric features.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Schapira AH, Tolosa E. Molecular and clinical prodrome of Parkinson disease: implications for treatment. Nat Rev Neurol. 2010;6:309–17. https://doi.org/10.1038/nrneurol.2010.52.
Klingelhoefer L, Samuel M, Chaudhuri KR, Ashkan K. An update of the impact of deep brain stimulation on non- motor symptoms in Parkinson’s disease. J Parkinsons Dis. 2014;4:289–300. https://doi.org/10.3233/JPD-130273.
Seppi K, et al. The movement disorder society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26(Suppl. 3):S42–80. https://doi.org/10.1002/mds.23884.
Hindle JV. Ageing, neurodegeneration and Parkinson’s disease. Age Ageining. 2010;39(2):156–611. https://doi.org/10.1093/ageing/afp223.
Chaudhuri KR, Healy DG, Schapira AH. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol. 2006;5:235–45. https://doi.org/10.1016/S1474-4422(06)70373-8.
Aaarslan D, Larsen JP, Tandberg E, Laake K. Predictors of nursing home placement in Parkinson’s disease: a population-based prospective study. J Am Geriatr Soc. 2000;48:938–42. https://doi.org/10.1111/j.1532-5415.2000.tb06891.
Chaudhuri KR, et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord. 2006;21:916–23. https://doi.org/10.1002/mds.20844.
Chaudhuri KR, et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov Disord. 2007;22:1901–11. https://doi.org/10.1002/mds.21596.
Chaudhuri KR, et al. King’s Parkinson’s disease pain scale, the first scale for pain in PD: an international validation. Mov Disord. 2015;30:1623–31. https://doi.org/10.1002/mdc3.12384.
Chaudhuri KR, Martinez-Martin P. Clinical assessment of nocturnal disability in Parkinson’s disease: the Parkinson’s disease Sleep Scale. Neurology. 2004;63:S17–20. https://doi.org/10.1212/wnl.63.8_suppl_3.s17.
Grinberg LT, Rueb U, Alho AT, Heinsen H. Brainstem pathology and non-motor symptoms in PD. J Neurol Sci. 2010;289:81–8. https://doi.org/10.1016/j.jns.2009.08.021.
Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23:837–44. https://doi.org/10.1002/mds.21956.
EmreM, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22(12):1689–1707. https://doi.org/10.1002/mds.21507.
Pigott K, Rick J, Xie SX, et al. Longitudinal study of normal cognition in Parkinson disease. Neurology. 2015;85(15):1276–82. https://doi.org/10.1212/WNL.0000000000002001.
Cereda E, Cilia R, Klersy C, et al. Dementia in Parkinson’s disease: is male gender a risk factor? Parkinsonism Relat Disord. 2016;26:67–72. https://doi.org/10.1016/j.parkreldis.2016.02.024.
Anang JB, Gagnon J-F, Bertrand J-A, et al. Predictors of dementia in Parkinson disease: a prospective cohort study. Neurology. 2014;83(14):1253–60. https://doi.org/10.1212/WNL.0000000000000842.
Kempster PA, O’Sullivan SS, Holton JL, Revesz T, Lees AJ. Relationships between age and late progression of Parkinson’s disease: a clinico-pathological study. Brain. 2010;133(Pt 6):1755–62. https://doi.org/10.1093/brain/awq059.
Monchi O, Hanganu A, Bellec P. Markers of cognitive decline in PD: The case for heterogeneity. Parkinsonism Relat Disord. 2016;24:8–14. https://doi.org/10.1016/j.parkreldis.2016.01.002.
Williams-Gray CH, Evans JR, Goris A, et al. The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the Cam-PaIGN cohort. Brain. 2009;132(Pt 11):2958–69. https://doi.org/10.1093/brain/awp245.
Svenningsson P, Westman E, Ballard C, Aarsland D. Cognitive impairment in patients with Parkinson’s disease: diagnosis, biomarkers, and treatment. Lancet Neurol. 2012;11:697–707. https://doi.org/10.1038/nrneurol.2017.27.
Litvan I, Goldman JG, Troster AI, et al. Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: movement disorder society task force guidelines. Mov Disord. 2012;27:349–56. https://doi.org/10.1002/mds.24893.
Halliday GM, Leverenz JB, Schneider JS, Adler CH. The neurobiological basis of cognitive impairment in Parkinson’s disease. Mov Disord. 2014;29:634–50. https://doi.org/10.1002/mds.25857.
Braak H, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24:197–211. https://doi.org/10.1016/s0197-4580(02)00065-9.
Compta Y, et al. Lewy- and Alzheimer-type pathologies in Parkinson’s disease dementia: which is more important? Brain. 2011;134:1493–505. https://doi.org/10.1093/brain/awr031.
Howlett DR, et al. Regional multiple pathology scores are associated with cognitive decline in Lewy body dementias. Brain Pathol. 2015;25:401–8. https://doi.org/10.1111/bpa.12182.
Backstrom DC, et al. Cerebrospinal fluid patterns and the risk of future dementia in early, incident Parkinson disease. JAMA Neurol. 2015;72:1175–82. https://doi.org/10.1001/jamaneurol.2015.1449.
Hall S, et al. CSF biomarkers and clinical progression of Parkinson disease. Neurology. 2015;84:57–63. https://doi.org/10.1001/jamaneurol.2015.1449.
Alves G, et al. CSF Aβ42 predicts early-onset dementia in Parkinson disease. Neurology. 2014;82:1784–90. https://doi.org/10.1212/WNL.0000000000000425.
Guella I, et al. α-Synuclein genetic variability: a biomarker for dementia in Parkinson disease. Ann Neurol. 2016;79:991–9. https://doi.org/10.1002/ana.24664.
Alcalay RN, et al. Cognitive performance of GBA mutation carriers with early-onset PD: the CORE-PD study. Neurology. 2012;78:1434–40. https://doi.org/10.1212/WNL.0b013e318253d54b.
Williams-Gray CH, et al. Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s disease. J Neurol. 2009;256:493–8. https://doi.org/10.1007/s00415-009-0119-8.
Morley JF, et al. Genetic influences on cognitive decline in Parkinson’s disease. Mov Disord. 2012;27:512–8. https://doi.org/10.1007/s00415-009-0119-8.
Seibert TM, Murphy EA, Kaestner EJ, Brewer JB. Interregional correlations in Parkinson disease and Parkinson-related dementia with resting functional MR imaging. Radiology. 2012;263:226–34. https://doi.org/10.1148/radiol.12111280.
Rektorova I, Krajcovicova L, Marecek R, Mikl M. Default mode network and extrastriate visual resting state network in patients with Parkinson’s disease dementia. Neurodegener Dis. 2012;10:232–7. https://doi.org/10.1002/gps.4342.
Vander Borght T, et al. Cerebral metabolic differences in Parkinson’s and Alzheimer’s diseases matched for dementia severity. J Nucl Med. 1997;38:797–802.
Gonzalez-Redondo R, et al. Grey matter hypometabolism and atrophy in Parkinson’s disease with cognitive impairment: a two-step process. Brain. 2014;137:2356–67. https://doi.org/10.1093/brain/awu159.
Kamei S, Morita A, Serizawa K, Mizutani T, Hirayanagi K. Quantitative EEG analysis of executive dysfunction in Parkinson disease. J Clin Neurophysiol. 2010;27:193–7. https://doi.org/10.1097/WNP.0b013e3181dd4fdb.
Klassen BT, et al. Quantitative EEG as a predictive biomarker for Parkinson disease dementia. Neurology. 2011;77:118–24. https://doi.org/10.1212/WNL.0b013e318224af8d.
Gratwicke J, et al. The nucleus basalis of Meynert: a new target for deep brain stimulation in dementia? Neurosci Biobehav Rev. 2013;37:2676–88. https://doi.org/10.1016/j.neubiorev.2013.09.003.
Parsons TD, Rogers SA, Braaten AJ, et al. Cognitive sequelae of subtalamic nucleus deep brain stimulation in Parkinson’s disease: a meta-analysis. Lancet Neurol. 2006;5:578–88. https://doi.org/10.1016/S1474-4422(06)70475-6.
Reijnders JS, Ehrt U, Weber WE, Aarsland D, Leentjens AF. A systematic review of prevalence studies of depression in Parkinson’s disease. Mov Disord. 2008;23:183–9. https://doi.org/10.1002/mds.21803.
Frisina PG, Borod JC, Foldi NS, Tenenbaum HR. Depression in Parkinson’s disease: health risks, etiology, and treatment options. Neuropsychiatr Dis Treat. 2008;4:81–91.
Rocha FL, Murad MG, Stumpf BP, Hara C, Fuzikawa C. Antidepressants for depression in Parkinson’s disease: systematic review and meta-analysis. J Psychopharmacol. 2013;27:417–23. https://doi.org/10.1177/0269881113478282.
Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain. 2005;128:1314–22. https://doi.org/10.1093/brain/awh445.
Henderson R, Kurlan R, Kersun JM, Como P. Preliminary examination of the comorbidity of anxiety and depression in Parkinson’s disease. J Neuropsychiatry Clin Neurosci. 1992;4(03):257–64. https://doi.org/10.1176/jnp.4.3.257.
Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE. Anxiety and motor fluctuations in Parkinson’s disease: a cross-sectional observational study. Parkinsonism Relat Disord. 2012;18(10):1084–8. https://doi.org/10.1016/j.parkreldis.2012.06.007.
Troeung L, Egan SJ, Gasson N. A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson’s disease. PLoS ONE. 2013;8:e79510. https://doi.org/10.1371/journal.pone.0079510.
Leentjens AF, Koester J, Fruh B, Shephard DT, Barone P, Houben JJ. The effect of pramipexole on mood and motivational symptoms in Parkinson’s disease: a meta-analysis of placebo-controlled studies. Clin Ther. 2009;31:89–98. https://doi.org/10.1016/j.clinthera.2009.01.012.
Barone P, Santangelo G, Morgante L, et al. A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson’s disease patients. Eur J Neurol. 2015;22:1184–91. https://doi.org/10.1111/ene.12724.
Xie C-L, Chen J, Wang X-D, et al. Repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in Parkinson disease: a meta-analysis of randomized controlled clinical trials. Neurol Sci. 2015;36(10):1751–61. https://doi.org/10.1007/s10072-015-2345-4.
Borisovskaya A, Bryson WC, Buchholz J, Samii A, Borson S. Electroconvulsive therapy for depression in Parkinson’s disease: systematic review of evidence and recommendations. Neurodegener Dis Manag. 2016;6(02):161–76. https://doi.org/10.2217/nmt-2016-0002.
Xie CL, Wang XD, Chen J, et al. A systematic review and meta-analysis of cognitive behavioral and psychodynamic therapy for depression in Parkinson’s disease patients. Neurol Sci. 2015;36:833–43. https://doi.org/10.1007/s10072-015-2118-0.
Deuschl G, Schade-Brittimger C, Krak P, et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006;355:896–908. https://doi.org/10.1056/NEJMoa060281.
Follett KA, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2010;362:2077–91. https://doi.org/10.2147/NDT.S105513.
Casteli L, et al. Chronic deep brain stimulation of the subthalamic nucleus for Parkinson’s disease: effect on cognition, mood, anxiety an personality traits. Eur Neurol. 2006;55:136–44. https://doi.org/10.1159/000093213.
Lin CH, Lin JW, Liu YC, Chang CH, Wu RM. Risk of Parkinson’s disease following anxiety disorders: a nationwide population-based cohort study. Eur J Neurol. 2015;22:1280–7. https://doi.org/10.1111/ene.12740.
Brown RG, et al. Depression and anxiety related subtypes in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2011;82:803–9.
Dissanayaka NNW, White E, O’Sullivan JD, Marsh R, Silburn PA, Copland DA, Mellick GD, Byrne GJ. Characteristics and Treatment of Anxiety Disorders in Parkinson’s Disease. Mov Disord Clin Pract. 2015;2:155–62.
Dissanayaka NNW, O’Sullivan JD, Silburn PA, Mellick GD. Assessment methods and factors associated with depression in Parkinson’s disease. J Neurol Sci. 2011;310:208–10. https://doi.org/10.1016/j.jad.2011.01.021.
Witt K, et al. Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson’s disease: a randomised, multicentre study. Lancet Neurol. 2008;7:605–14. https://doi.org/10.1016/S1474-4422(08)70114-5.
Pedersen KF, et al. Apathy in drug-naive patients with incident Parkinson’s disease: the Norwegian Park West study. J Neurol. 2010;257:217–23. https://doi.org/10.1007/s00415-009-5297-x.
den Brok MG, van Dalen JW, van Gool WA, Moll van Charante EP, de Bie RM, Richard E. Apathy in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 2015;30(06): 759–69. https://doi.org/10.1002/mds.26208.
Maillet A, Krack P, Lhommée E, et al. The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson’s disease. Brain. 2016;139(Pt 9):2486–502. https://doi.org/10.1093/brain/aww162.
Thobois S, et al. Non-motor dopamine withdrawal syndrome after surgery for Parkinson’s disease: predictors and underlying mesolimbic denervation. Brain. 2010;133:1111–27. https://doi.org/10.1093/brain/awq032.
Del SF, Albanese A. Clinical management of pain and fatigue in Parkinson’s disease. Parkinsonism Relat Disord. 2012;18(Suppl. 1):S233–6. https://doi.org/10.1016/S1353-8020(11)70071-2.
Hagell P, Brundin L. Towards an understanding of fatigue in Parkinson disease. J Neurol Neurosurg Psychiatry. 2009;80:489–92. https://doi.org/10.1136/jnnp.2008.159772.
Moore TJ, Glenmullen J, Mattison DR. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern Med. 2014;174(12):1930–3. https://doi.org/10.1001/jamainternmed.2014.5262.
Evans AH, Lawrence AD, Potts J, Appel S, Lees AJ. Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease. Neurology. 2005;65(10):1570–4. https://doi.org/10.1212/01.wnl.0000184487.72289.f0.
Shotbolt P, et al. Relationships between deep brain stimulation and impulse control disorders in Parkinson’s disease, with a literature review. Parkinsonism Relat. Disord. 2012;18:10–6. https://doi.org/10.1016/j.parkreldis.2011.08.016.
Zahodne LB, Fernandez HH. Pathophysiology and treatment of psychosis in Parkinson’s disease: a review. Drugs Aging. 2008;25:665–82. https://doi.org/10.2165/00002512-200825080-00004.
Papapetropoulos S, McCorquodale DS, Gonzalez J, Jean-Gilles L, Mash DC. Cortical and amygdalar Lewy body burden in Parkinson’s disease patients with visual hallucinations. Parkinsonism Relat Disord. 2006;12:253–6. https://doi.org/10.1016/j.parkreldis.2005.10.005.
Mundt-Petersen U, Odin P. Infusional therapies, continuous dopaminergic stimulation, and nonmotor symptoms. In: Chaudhuri R, Titova N, editors, Parkinson’s: the hidden face management and the hidden face of related disorders. Elsevier. 2017. p. 1019–44. (International Review of Neurobiology). https://doi.org/10.1016/bs.irn.2017.05.036.
Ray Chaudhuri K, Antonini A, Robieson WZ, Sanchez-Solino O, Bergmann L, Poewe W, et al. Burden of non-motor symptoms in Parkinson’s disease patients predicts improvement in quality of life during treatment with levodopa-carbidopa intestinal gel. Eur J Neurol. 2019;26(4):581–e43. https://doi.org/10.1111/ene.13847.
Dafsari HS, Martinez-Martin P, Rizos A, Trost M, Dos Santos Ghilardi MG, Reddy P, et al. EuroInf 2: subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson’s disease. Mov Disord. 2019;34:353–65. https://doi.org/10.1002/mds.27626.
Titova N, Chaudhuri KR. Non-motor Parkinson disease: new concepts and personalised management. Med J Australia. 2018;208(9):404–9. https://doi.org/10.5694/mja17.00993.
Seppi K, Ray Chaudhuri K, Coelho M, Fox SH, Katzenschlager R, Perez Lloret S, Weintraub D, Sampaio C. The collaborators of the Parkinson’s disease update on non-motor symptoms study group on behalf of the movement disorders society evidence-based medicine committee update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov Disord. 2019;34:180–98. https://doi.org/10.1002/mds.27602.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Vuletić, V. (2020). Non-motor Symptoms in Parkinson’s Disease. In: Demarin, V. (eds) Mind and Brain. Springer, Cham. https://doi.org/10.1007/978-3-030-38606-1_9
Download citation
DOI: https://doi.org/10.1007/978-3-030-38606-1_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-38605-4
Online ISBN: 978-3-030-38606-1
eBook Packages: MedicineMedicine (R0)