4,043
Views
13
CrossRef citations to date
0
Altmetric
Review

Non-motor complications in late stage Parkinson’s disease: recognition, management and unmet needs

ORCID Icon, , , , & ORCID Icon
Pages 335-352 | Received 24 Nov 2020, Accepted 27 Jan 2021, Published online: 16 Feb 2021

References

  • Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013.
  • Titova N, Chaudhuri KR. Non-motor Parkinson disease: new concepts and personalised management. Med J Aust. 2018;208(9):404–409.
  • Holloway RG, Shoulson I, Fahn S, et al. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol. 2004;61(7):1044–1053.
  • Coelho M, Ferreira JJ. Late-stage Parkinson disease. Nat Rev Neurol. 2012;8(8):435–442.
  • Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci. 2017;18(8):509.
  • Sauerbier A, Jenner P, Todorova A, et al. Non motor subtypes and Parkinson’s disease. Parkinsonism Relat Disord. 2016;22(Suppl 1):S41–6.
  • Marras C, Chaudhuri KR. Nonmotor features of Parkinson’s disease subtypes. Mov Disord. 2016;31(8):1095–1102.
  • Antonini A, Stoessl AJ, Kleinman LS, et al. Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson’s disease: a multi-country Delphi-panel approach. Curr Med Res Opin. 2018;34(12):2063–2073.
  • Fasano A, Fung VSC, Lopiano L, et al. Characterizing advanced Parkinson’s disease: OBSERVE-PD observational study results of 2615 patients. BMC Neurol. 2019;19(1):50.
  • Martinez-Martin P, Ray Chaudhuri K. Comprehensive grading of Parkinson’s disease using motor and non-motor assessments: addressing a key unmet need. Expert Rev Neurother. 2018;18(1):41–50.
  • Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology. 1967;17(5):427–442.
  • Chaudhuri KR, Martinez-Martin P, Schapira AH, 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;6(1):916–923. .
  • Titova N, Martinez-Martin P, Katunina E, et al. Advanced Parkinson’s or “complex phase” Parkinson’s disease? Re-evaluation is needed. J Neural Transm. 2017;6(1):1529–1537.
  • Chaudhuri KR, Sauerbier A, Rojo JM, et al. The burden of non-motor symptoms in Parkinson’s disease using a self-completed non-motor questionnaire: a simple grading system. Parkinsonism Relat Disord. 2015;21(3):287–291.
  • Pavy-Le Traon A, Amarenco G, Duerr S, et al. The Movement Disorders task force review of dysautonomia rating scales in Parkinson’s disease with regard to symptoms of orthostatic hypotension. Mov Disord. 2011;26(11):1985–1992.
  • Perez-Lloret S, Ciampi de Andrade D, KE L, et al. Rating Scales for Pain in Parkinson’s Disease: critique and Recommendations. Mov Disord Clin Pract. 2016;3(6):527–537.
  • Friedman JH, Alves G, Hagell P, et al. Fatigue rating scales critique and recommendations by the Movement Disorders Society task force on rating scales for Parkinson’s disease. Mov Disord. 2010;25(7):805–822.
  • Schrag A, Barone P, Brown RG, et al. Depression rating scales in Parkinson‘s disease: critique and recommendations. Mov Disord. 2007;22(8):1077–1092.
  • Hogl B, Arnulf I, Comella C, et al. Scales to assess sleep impairment in Parkinson’s disease: critique and recommendations. Mov Disord. 2010;25(16):2704–2716.
  • Mollenhauer B, Zimmermann J, Sixel-Doring F, et al. Baseline predictors for progression 4 years after Parkinson’s disease diagnosis in the De Novo Parkinson Cohort (DeNoPa). Mov Disord. 2019;34(1):67–77.
  • Hely MA, Reid WG, Adena MA, et al. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837–844.
  • Williams-Gray CH, Mason SL, Evans JR, et al. The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J Neurol Neurosurg Psychiatry. 2013;84(11):1258–1264.
  • Cholerton BA, Zabetian CP, Quinn JF, et al. Pacific Northwest Udall Center of excellence clinical consortium: study design and baseline cohort characteristics. J Parkinsons Dis. 2013;3(2):205–214.
  • 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(3):349–356.
  • Lauze M, Daneault JF, Duval C. The Effects of Physical Activity in Parkinson’s Disease: a Review. J Parkinsons Dis. 2016;6(4):685–698.
  • da Silva FC, Iop RDR, de Oliveira LC, et al. Effects of physical exercise programs on cognitive function in Parkinson’s disease patients: a systematic review of randomized controlled trials of the last 10 years. PloS One. 2018;13(2):e0193113.
  • Stuckenschneider T, Askew CD, Meneses AL, et al. The Effect of Different Exercise Modes on Domain-Specific Cognitive Function in Patients Suffering from Parkinson’s Disease: a Systematic Review of Randomized Controlled Trials. J Parkinsons Dis. 2019;9(1):73–95.
  • Bohnen JLB, Muller M, Haugen J, et al. Mentally stimulating activities associate with better cognitive performance in Parkinson disease. J Neural Transm. 2017;124(10):1205–1212.
  • Wang HX, Karp A, Winblad B, et al. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen project. Am J Epidemiol. 2002;155(12):1081–1087.
  • Hindle JV, Hurt CS, Burn DJ, et al. The effects of cognitive reserve and lifestyle on cognition and dementia in Parkinson’s disease—a longitudinal cohort study. Int J Geriatr Psychiatry. 2016;31(1):13–23.
  • Goldman JG, Weintraub D. Advances in the treatment of cognitive impairment in Parkinson’s disease. Mov Disord. 2015;30(11):1471–1489.
  • Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov Disord. 2019;34(2):180–198.
  • Weintraub D, Caspell-Garcia C, Simuni T, et al. Neuropsychiatric symptoms and cognitive abilities over the initial quinquennium of Parkinson disease. Ann Clin Transl Neurol. 2020;7(4):449–461.
  • Cai X, Campbell N, Khan B, et al. Long-term anticholinergic use and the aging brain. Alzheimers Dement. 2013;9(4):377–385.
  • Marras C, Chaudhuri KR, Titova N, et al. Therapy of Parkinson’s Disease Subtypes. Neurotherapeutics. 2020;17(4):1366–1377.
  • Centi J, Freeman R, Gibbons CH, et al. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology. 2017;88(1):17–24.
  • Kaminska M, Mery VP, Lafontaine AL, et al. Change in Cognition and Other Non-Motor Symptoms With Obstructive Sleep Apnea Treatment in Parkinson Disease. J Clin Sleep Med. 2018;14(5):819–828.
  • Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004;351(24):2509–2518.
  • Emre M, Poewe W, De Deyn PP, et al. Long-term safety of rivastigmine in Parkinson disease dementia: an open-label, randomized study. Clin Neuropharmacol. 2014;37(1):9–16.
  • Dubois B, Tolosa E, Katzenschlager R, et al. Donepezil in Parkinson’s disease dementia: a randomized, double-blind efficacy and safety study. Mov Disord. 2012;27(10):1230–1238.
  • Litvinenko IV, Odinak MM, Mogil’naya VI, et al. Efficacy and safety of galantamine (reminyl) for dementia in patients with Parkinson’s disease (an open controlled trial). Neurosci Behav Physiol. 2008;38(9):937–945.
  • Leroi I, Overshott R, Byrne EJ, et al. Randomized controlled trial of memantine in dementia associated with Parkinson’s disease. Mov Disord. 2009;24(8):1217–1221.
  • Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinson’s disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol. 2009;8(7):613–618.
  • Emre M, Tsolaki M, Bonuccelli U, et al. Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(10):969–977.
  • Martinez-Martin P, Reddy P, Katzenschlager R, et al. EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson’s disease. Mov Disord. 2015;30(4):510–516.
  • Dafsari HS, Martinez-Martin P, Rizos A, et al. EuroInf 2: subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson’s disease. Mov Disord. 2019;34(3):353–365.
  • Lim EW, Aarsland D, Ffytche D, et al. Amyloid-beta and Parkinson‘s disease. J Neurol. 2019;266(11):2605–2619.
  • van Wamelen D, Politis M, Aarsland D, et al. APOmorphine infusion and aMYLoid deposition in Parkinson’s disease (APOMYL): preliminary clinical and amyloid imaging data (P3.8-032). Neurology. 2019;92(15Supplement):P3.8–032.
  • Leung IH, Walton CC, Hallock H, et al. Cognitive training in Parkinson disease: a systematic review and meta-analysis. Neurology. 2015;85(21):1843–1851.
  • Lawrence BJ, Gasson N, Johnson AR, et al. Cognitive Training and Transcranial Direct Current Stimulation for Mild Cognitive Impairment in Parkinson’s Disease: a Randomized Controlled Trial. Parkinsons Dis. 2018;4318475.
  • Orgeta V, McDonald KR, Poliakoff E, et al. Cognitive training interventions for dementia and mild cognitive impairment in Parkinson’s disease. Cochrane Database Syst Rev. 2020;2:CD011961.
  • Nousia A, Martzoukou M, Tsouris Z, et al. The Beneficial Effects of Computer-Based Cognitive Training in Parkinson’s Disease: a Systematic Review. Arch Clin Neuropsychol. 2020;35(4):434–447.
  • Dinkelbach L, Brambilla M, Manenti R, et al. Non-invasive brain stimulation in Parkinson’s disease: exploiting crossroads of cognition and mood. Neurosci Biobehav Rev. 2017;75:407–418.
  • Storch A, Schneider CB, Wolz M, et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology. 2013;80(9):800–809.
  • Antonini A, Leta V, Teo J, et al. Outcome of Parkinson’s Disease Patients Affected by COVID-19. Mov Disord. 2020;35(6):905–908.
  • Sulzer D, Antonini A, Leta V, et al. COVID-19 and possible links with Parkinson’s disease and parkinsonism: from bench to bedside. NPJ Parkinsons Dis. 2020;6(1):18.
  • Chandler SK, Robins JL, Kinser PA. Nonpharmacologic Interventions for the Self-Management of Anxiety in Parkinson’s Disease: a Comprehensive Review. Behav Neurol. 2019;8459579.
  • Pontone GM, Dissanayaka N, Apostolova L, et al. Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson’s disease. NPJ Parkinson’s Dis. 2019;5(1):30.
  • Dobkin RD, Menza M, Allen LA, et al. Cognitive-behavioral therapy for depression in Parkinson’s disease: a randomized, controlled trial. Am J Psychiatry. 2011;168(10):1066–1074.
  • Yang S, Sajatovic M, Walter BL. Psychosocial interventions for depression and anxiety in Parkinson’s disease. J Geriatr Psychiatry Neurol. 2012;25(2):113–121.
  • Troeung L, Egan SJ, Gasson N. A waitlist-controlled trial of group cognitive behavioural therapy for depression and anxiety in Parkinson’s disease. BMC Psychiatry. 2014;14:19.
  • Calleo JS, Amspoker AB, Sarwar AI, et al. A Pilot Study of a Cognitive-Behavioral Treatment for Anxiety and Depression in Patients With Parkinson Disease. J Geriatr Psychiatry Neurol. 2015;28(3):210–217.
  • Weintraub D. Management of psychiatric disorders in Parkinson’s disease: neurotherapeutics — movement Disorders Therapeutics. Neurotherapeutics. 2020;17(4):1511–1524.
  • Schrag A, Hommel A, Lorenzl S, et al. The late stage of Parkinson’s -results of a large multinational study on motor and non-motor complications. Parkinsonism Relat Disord. 2020;75:91–96.
  • Collerton D, Taylor JP. Advances in the treatment of visual hallucinations in neurodegenerative diseases. Future Neurol. 2013;8(4):433–444.
  • Diederich NJ, Pieri V, Goetz CG. Coping strategies for visual hallucinations in Parkinson’s disease. Mov Disord. 2003;18(7):831–832.
  • Barnes J, Connelly V, Boubert L, et al. Behavioural coping patterns in Parkinson’s patients with visual hallucinations. J Neuropsychol. 2013;7(2):326–334.
  • Thomsen TR, Panisset M, Suchowersky O, et al. Impact of standard of care for psychosis in Parkinson disease. J Neurol Neurosurg Psychiatry. 2008;79(12):1413–1415.
  • Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014;383(9916):533–540.
  • Ondo WG, Tintner R, Voung KD, et al. Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson’s disease. Mov Disord. 2005;20(8):958–963.
  • Rabey JM, Prokhorov T, Miniovitz A, et al. Effect of quetiapine in psychotic Parkinson’s disease patients: a double-blind labeled study of 3 months’ duration. Mov Disord. 2007;22(3):313–318.
  • Shotbolt P, Samuel M, Fox C, et al. A randomized controlled trial of quetiapine for psychosis in Parkinson’s disease. Neuropsychiatr Dis Treat. 2009;5:327–332.
  • Zahodne LB, Fernandez HH. Pathophysiology and treatment of psychosis in Parkinson’s disease: a review. Drugs Aging. 2008;25(8):665–682.
  • Kaufmann H, Palma JA. Neurogenic orthostatic hypotension: the very basics. Clin Auton Res. 2017;27(Suppl1):39–43.
  • Fanciulli A, Campese N, Goebel G, et al. Association of transient orthostatic hypotension with falls and syncope in patients with Parkinson disease. Neurology. 2020;95(21):e2854–e65.
  • Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. 2017;264(8):1567–1582.
  • Espay AJ, LeWitt PA, Hauser RA, et al. Neurogenic orthostatic hypotension and supine hypertension in Parkinson’s disease and related synucleinopathies: prioritisation of treatment targets. Lancet Neurol. 2016;15(9):954–966.
  • Palma JA, Kaufmann H. Orthostatic Hypotension in Parkinson Disease. Clin Geriatr Med. 2020;36(1):53–67.
  • Kaufmann H, Malamut R, Norcliffe-Kaufmann L, et al. The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res. 2012;22(2):79–90.
  • Palma JA, Gomez-Esteban JC, Norcliffe-Kaufmann L, et al. Orthostatic hypotension in Parkinson disease: how much you fall or how low you go? Mov Disord. 2015;30(5):639–645.
  • Merola A, Romagnolo A, Rosso M, et al. Orthostatic hypotension in Parkinson’s disease: does it matter if asymptomatic? Parkinsonism & related disorders. 2016;33:65–71.
  • Palma JA, Kaufmann H. Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies. Mov Disord. 2018;33(3):372–390.
  • Kaufmann H, Freeman R, Biaggioni I, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328–335.
  • Schoffer KL, Henderson RD, O’Maley K, et al. Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson’s disease. Mov Disord. 2007;22(11):1543–1549.
  • Chen JJ, Han Y, Tang J, et al. Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: a Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials. Ann Pharmacother. 2018;52(12):1182–1194.
  • Okamoto LE, Diedrich A, Baudenbacher FJ, et al. Efficacy of Servo-Controlled Splanchnic Venous Compression in the Treatment of Orthostatic Hypotension: a Randomized Comparison With Midodrine. Hypertension. 2016;68(2):418–426.
  • Fanciulli A, Goebel G, Metzler B, et al. Elastic Abdominal Binders Attenuate Orthostatic Hypotension in Parkinson‘s Disease. Mov Disord Clin Pract. 2016;3(2):156–160.
  • Kurtis MM, Rajah T, Delgado LF, et al. The effect of deep brain stimulation on the non-motor symptoms of Parkinson’s disease: a critical review of the current evidence. NPJ Parkinsons Dis. 2017;3:16024.
  • Norcliffe-Kaufmann L, Kaufmann H Autonomic dysfunction in Parkinson’s disease. Parkinson’s Disease: diagnosis, Motor Symptoms and Non-Motor Features: Future Medicine Ltd; 2013. P. 79–98.
  • Batla A, Tayim N, Pakzad M, et al. Treatment Options for Urogenital Dysfunction in Parkinson’s Disease. Curr Treat Options Neurol. 2016;18(10):45.
  • Madan A, Ray S, Burdick D, et al. Management of lower urinary tract symptoms in Parkinson’s disease in the neurology clinic. Int J Neurosci. 2017;127(12):1136–1149.
  • Gubbiotti M, Conte A, Di Stasi SM, et al. Feasibility of mirabegron in the treatment of overactive bladder in patients affected by Parkinson’s disease: a pilot study. Ther Adv Neurol Disord. 2019;12:1756286419843458.
  • Vaughan CP, Burgio KL, Goode PS, et al. Behavioral therapy for urinary symptoms in Parkinson’s disease: a randomized clinical trial. Neurourol Urodyn. 2019;38(6):1737–1744.
  • Dafsari HS, Silverdale M, Strack M, et al. Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson’s disease. Mov Disord. 2018;33(3):421–430.
  • American College of Gastroenterology Chronic Constipation Task F. An evidence-based approach to the management of chronic constipation in. North America. Am J Gastroenterol. 2005;100(Suppl 1):S1–4.
  • Mendoza-Velasquez JJ, Flores-Vazquez JF, Barron-Velazquez E, et al. Autonomic Dysfunction in alpha-Synucleinopathies. Front Neurol. 2019;10:363.
  • Chen Z, Li G, Liu J. Autonomic dysfunction in Parkinson’s disease: implications for pathophysiology, diagnosis, and treatment. Neurobiol Dis. 2020;134:104700.
  • Barichella M, Pacchetti C, Bolliri C, et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: an RCT. Neurology. 2016;87(12):1274–1280.
  • Zangaglia R, Martignoni E, Glorioso M, et al. Macrogol for the treatment of constipation in Parkinson‘s disease. A randomized placebo-controlled study. Mov Disord. 2007;22(9):1239–1244. .
  • Ondo WG, Kenney C, Sullivan K, et al. Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease. Neurology. 2012;78(21):1650–1654. .
  • Fasano A, Visanji NP, Liu LW, et al. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14(6):625–639.
  • Reynolds H, Miller N, Walker R. Drooling in Parkinson’s Disease: evidence of a Role for Divided Attention. Dysphagia. 2018;33(6):809–817.
  • van Wamelen DJ, Leta V, Johnson J, et al. Drooling in Parkinson’s Disease: prevalence and Progression from the Non-motor International Longitudinal Study. Dysphagia. 2020;35(6):955–961. .
  • Arbouw ME, Movig KL, Koopmann M, et al. Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology. 2010;74(15):1203–1207. .
  • Chinnapongse R, Gullo K, Nemeth P, et al. Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson’s disease: a prospective double-blind trial. Mov Disord. 2012;27(2):219–226.
  • Sridharan K, Sivaramakrishnan G. Pharmacological interventions for treating sialorrhea associated with neurological disorders: a mixed treatment network meta-analysis of randomized controlled trials. J Clin Neurosci. 2018;51:12–17.
  • Egevad G, Petkova VY, Vilholm OJ. Sialorrhea in patients with Parkinson’s disease: safety and administration of botulinum neurotoxin. J Parkinsons Dis. 2014;4(3):321–326.
  • Valkovic P, Minar M, Singliarova H, et al. Pain in Parkinson´s Disease: a Cross-Sectional Study of Its Prevalence, Types, and Relationship to Depression and Quality of Life. PloS One. 2015;10(8):e0136541. .
  • Buhidma Y, Rukavina K, Chaudhuri KR, et al. Potential of animal models for advancing the understanding and treatment of pain in Parkinson’s disease. NPJ Parkinsons Dis. 2020;6(1):1.
  • Rukavina K, Leta V, Sportelli C, et al. Pain in Parkinsonʼs disease. Curr Opin Neurol. 2019;32(4):579–588. .
  • Ghosh P, Imbriani P, Caputi N, et al. A Dual Centre Study of Pain in Parkinson’s Disease and Its Relationship with Other Non-Motor Symptoms. J Parkinsons Dis. 2020;10(4):1817–1825. .
  • Tan Y, Tan J, Deng J, et al. Alteration of Basal Ganglia and Right Frontoparietal Network in Early Drug-Café Parkinson’s Disease during Heat Pain Stimuli and Resting State. Front Hum Neurosci. 2015;9:467.
  • Putcha D, Ross RS, Cronin-Golomb A, et al. Altered intrinsic functional coupling between core neurocognitive networks in Parkinson’s disease. Neuroimage Clin. 2015;7:449–455.
  • Chaudhuri KR, Rizos A, Trenkwalder C, et al. King’s Parkinson’s disease pain scale, the first scale for pain in PD: an international validation. Mov Disord. 2015;30(12):1623–1631. .
  • Myers PS, Harrison EC, Rawson KS, et al. Yoga Improves Balance and Low-Back Pain, but Not Anxiety, in People with Parkinson’s Disease. Int J Yoga Therap. 2020;30(1):41–48. .
  • Nguy V, Barry BK, Moloney N, et al. Exercise-induced hypoalgesia is present in people with Parkinson’s disease: two observational cross-sectional studies. European Journal of Pain (London, England). 2019;23(7):1329–1339.
  • NE A, Moloney N, van Vliet V, et al. The Rationale for Exercise in the Management of Pain in Parkinson’s Disease. J Parkinsons Dis. 2015;10(8):229–239.
  • Skogar O, Lokk J. Pain management in patients with Parkinson’s disease: challenges and solutions. J Multidiscip Healthc. 2016;9:469–479.
  • Trenkwalder C, Chaudhuri KR, Martinez-Martin P, et al. Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson’s disease (PANDA): a double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2015;14(12):1161–1170. .
  • Thakur D, Dickerson S, Kumar Bhutani M, et al. Impact of Prolonged-release Oxycodone/Naloxone on Outcomes Affecting Patients‘ Daily Functioning in Comparison With Extended-release Tapentadol: a Systematic Review. Clin Ther. 2015;37(1):212–224.
  • Guerriero F, Roberto A, Greco MT, et al. Long-term efficacy and safety of oxycodone-naloxone prolonged release in geriatric patients with moderate-to-severe chronic noncancer pain: a 52-week open-label extension phase study. Drug Des Devel Ther. 2016;10:1515–1523.
  • Rascol O, Zesiewicz T, Chaudhuri KR, et al. A Randomized Controlled Exploratory Pilot Study to Evaluate the Effect of Rotigotine Transdermal Patch on Parkinson’s Disease-Associated Chronic Pain. J Clin Pharmacol. 2016;56(7):852–861. .
  • Zella MAS, May C, Muller T, et al. Landscape of pain in Parkinson’s disease: impact of gender differences. Neurol Res. 2019;41(1):87–97. .
  • Buhmann C, Wrobel N, Grashorn W, et al. Pain in Parkinson disease: a cross-sectional survey of its prevalence, specifics, and therapy. J Neurol. 2017;264(4):758–769. .
  • Buhmann C, Kassubek J, Jost WH. Management of Pain in Parkinson’s Disease. J Parkinsons Dis. 2020;10(s1):S37–S48.
  • Djaldetti R, Yust-Katz S, Kolianov V, et al. The effect of duloxetine on primary pain symptoms in Parkinson disease. Clin Neuropharmacol. 2007;22(9):1239–1244.
  • Yu SW, Lin SH, Tsai CC, et al. Acupuncture Effect and Mechanism for Treating Pain in Patients With Parkinson’s Disease. Front Neurol. 2019;10:1114.
  • Chakravarthy KV, Chaturvedi R, Agari T, et al. Single arm prospective multicenter case series on the use of burst stimulation to improve pain and motor symptoms in Parkinson’s disease. Bioelectron Med. 2020;6(18). DOI: 10.1186/s42234-020-00055-3.
  • Loddo G, Calandra-Buonaura G, Sambati L, et al. The Treatment of Sleep Disorders in Parkinson’s Disease: from Research to Clinical Practice. Front Neurol. 2017;8:42.
  • Peeraully T, Yong M-H, Chokroverty S, et al. Sleep and Parkinson’s disease: a review of case-control polysomnography studies. Mov Disord. 2012;27(14):1729–1737.
  • Zhang Y, Zhao JH, Huang DY, et al. Multiple comorbid sleep disorders adversely affect quality of life in Parkinson’s disease patients. NPJ Parkinsons Dis. 2020;6(1):25. .
  • Xu Z, Anderson KN, Saffari SE, et al. Progression of sleep disturbances in Parkinson’s disease: a 5-year longitudinal study. J Neurol. 2021;268(1):312–320.
  • Barone P, Antonini A, Colosimo C, et al. The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord. 2009;24(11):1641–1649.
  • JRP Z, During EH. Sleep Issues in Parkinson’s Disease and Their Management. Neurotherapeutics. 2020 Oct;17(4):1480–1494.
  • Dhawan V, Healy DG, Pal S, et al. Sleep-related problems of Parkinson’s disease. Age Ageing. 2006;35(3):220–228.
  • Gros P, Videnovic A. Sleep and Circadian Rhythm Disorders in Parkinson’s Disease. 2017;3(3):222–234. Curr Sleep Med Rep.
  • Garcia-Borreguero D, Larrosa O, Bravo M. Parkinson’s disease and sleep. Sleep Med Rev. 2003;7(2):115–129.
  • Liu CF, Wang T, Zhan SQ, et al. Management Recommendations on Sleep Disturbance of Patients with Parkinson’s Disease. Chin Med J (Engl). 2018;131(24):2976–2985.
  • Klingelhoefer L, Rizos A, Sauerbier A, et al. Night-time sleep in Parkinson’s disease — the potential use of Parkinson’s KinetiGraph: a prospective comparative study. Eur J Neurol. 2016;23(8):1275–1288.
  • Pierantozzi M, Placidi F, Liguori C, et al. Rotigotine may improve sleep architecture in Parkinson’s disease: a double-blind, randomized, placebo-controlled polysomnographic study. Sleep Med. 2016;21:140–144.
  • Trenkwalder C, Kies B, Rudzinska M, et al. Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord. 2011;26(1):90–99.
  • Menza M, Dobkin RD, Marin H, et al. Treatment of insomnia in Parkinson’s disease: a controlled trial of eszopiclone and placebo. Mov Disord. 2010;25(11):1708–1714.
  • Dowling GA, Mastick J, Colling E, et al. Melatonin for sleep disturbances in Parkinson’s disease. Sleep Med. 2005;6(5):459–466.
  • Videnovic A, Klerman EB, Wang W, et al. Timed Light Therapy for Sleep and Daytime Sleepiness Associated With Parkinson Disease: a Randomized Clinical Trial. JAMA Neurol. 2017;74(4):411–418.
  • Zeng BY, Zhao K. Effect of Acupuncture on the Motor and Nonmotor Symptoms in Parkinson’s Disease—A Review of Clinical Studies. CNS Neurosci Ther. 2016;22(5):333–341.
  • Gjerstad MD, Alves G, Wentzel-Larsen T, et al. Excessive daytime sleepiness in Parkinson disease: is it the drugs or the disease? Neurology. 2006;67(5):853–858.
  • Amara AW, Chahine LM, Caspell-Garcia C, et al. Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2017;88(8):653–662.
  • Breen DP, Williams-Gray CH, Mason SL, et al. Excessive daytime sleepiness and its risk factors in incident Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2013;84(2):233–234.
  • Zesiewicz TA, Hauser RA. Sleep attacks and dopamine agonists for Parkinson’s disease: what is currently known? CNS Drugs. 2003;17(8):593–600.
  • Hauser RA, Gauger L, Anderson WM, et al. Pramipexole-induced somnolence and episodes of daytime sleep. Mov Disord. 2000;15(4):658–663.
  • Ferreira JJ, Galitzky M, Thalamas C, et al. Effect of ropinirole on sleep onset: a randomized, placebo-controlled study in healthy volunteers. Neurology. 2002;58(3):460–462.
  • Paus S, Brecht HM, Koster J, et al. Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson’s disease. Mov Disord. 2003;18(6):659–667.
  • Stefani A, Hogl B. Sleep in Parkinson’s disease. Neuropsychopharmacology. 2020;45(1):121–128.
  • Hogl B, Saletu M, Brandauer E, et al. Modafinil for the treatment of daytime sleepiness in Parkinson’s disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial. Sleep. 2002;25(8):905–909.
  • Adler CH, Caviness JN, Hentz JG, et al. Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson’s disease. Mov Disord. 2003;18(3):287–293.
  • Postuma RB, Anang J, Pelletier A, et al. Caffeine as symptomatic treatment for Parkinson disease (Café-PD): a randomized trial. Neurology. 2017;89(17):1795–1803.
  • Postuma RB, Lang AE, Munhoz RP, et al. Caffeine for treatment of Parkinson disease: a randomized controlled trial. Neurology. 2012;79(7):651–658.
  • Weintraub D, Mavandadi S, Mamikonyan E, et al. Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology. 2010;75(5):448–455.
  • Devos D, Krystkowiak P, Clement F, et al. Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2007;78(5):470–475.
  • Suzuki K, Miyamoto M, Miyamoto T, et al. Istradefylline improves daytime sleepiness in patients with Parkinson’s disease: an open-label, 3-month study. J Neurol Sci. 2017;380:230–233.
  • Ondo WG, Perkins T, Swick T, et al. Sodium oxybate for excessive daytime sleepiness in Parkinson disease: an open-label polysomnographic study. Arch Neurol. 2008;65(10):1337–1340.
  • Martinez-Martin P, Wan YM, Ray Chaudhuri K, et al. Impulse control and related behaviors in Parkinson’s disease with dementia. Eur J Neurol. 2020;27(6):944–950.
  • Fauser M, Lohle M, Ebersbach G, et al. Intraindividual Variability of Nonmotor Fluctuations in Advanced Parkinson’s Disease. J Parkinsons Dis. 2015;5(4):737–741.
  • Martinez-Fernandez R, Schmitt E, Martinez-Martin P, et al. The hidden sister of motor fluctuations in Parkinson’s disease: a review on nonmotor fluctuations. Mov Disord. 2016;31(8):1080–1094.
  • Chaudhuri KR, Rizos A, Sethi KD. Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery? J Neural Transm. 2013;120(9):1305–1320.
  • Martinez-Martin P, Schrag A, Weintraub D, et al. Pilot Study of the International Parkinson and Movement Disorder Society-sponsored Non-motor Rating Scale (MDS-NMS). Mov Disord Clin Pract. 2019;6(3):227–234.
  • Martinez-Martin P, Rojo-Abuin JM, Weintraub D, et al. Factor Analysis and Clustering of the Movement Disorder Society-Non-Motor Rating Scale. Mov Disord. 2020;35(6):969–975.
  • Chaudhuri KR, Schrag A, Weintraub D, et al. The movement disorder society nonmotor rating scale: initial validation study. Mov Disord. 2020;35(1):116–133.
  • Tenison E, Henderson EJ. Multimorbidity and Frailty: tackling Complexity in Parkinson’s Disease. J Parkinsons Dis. 2020;10(s1):S85–S91.