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Parkinson's disease: treatment and non-motor features

Published online by Cambridge University Press:  12 June 2012

Graeme JA Macphee*
Affiliation:
Department of Medicine for the Elderly/Movement Disorders Clinic, Southern General Hospital/Victoria Infirmary, Glasgow, UK
David A Stewart
Affiliation:
Department of Medicine for the Elderly/Movement Disorders Clinic, Southern General Hospital/Victoria Infirmary, Glasgow, UK
*
Address for correspondence: GJA Macphee, Consultant/Honorary Clinical Senior Lecturer, Department of Medicine for the Elderly/Movement Disorders Clinic, Southern General Hospital, Glasgow G51 4TF. Email: Graeme.Macphee@ggc.scot.nhs.uk

Summary

This review on Parkinson's disease (PD) considers pharmacological and surgical management and important non-motor symptoms (NMS) such as depression, dementia and sleep disorder. In the absence of a proven neuroprotective drug, therapy remains symptomatic and may be initiated with levodopa or a dopamine agonist or a monoamine oxidase inhibitor. Treatment should be tailored to the individual patient, with patient preference, extent of functional impairment and co-morbidity more important than age per se. As disease progresses, therapy usually becomes more complex and apomorphine, duodopa and surgical intervention may be useful.

NMS may be present at any stage of illness but become more common in severity and frequency with advanced disease, when neuropsychiatric features such as dementia and psychosis dominate the clinical picture. NMS are often unrecognized and undeclared by patients and carers in clinic. Novel agents for treating non-motor features, which are often poorly responsive to dopaminergic therapy, are urgently required.

Type
Clinical geriatrics
Copyright
Copyright © Cambridge University Press 2012

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References

1Chase, TN, Oh, JD. Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications. Ann Neurol 2000; 47 (suppl 1): 122–30.Google ScholarPubMed
2Olanow, CW, Obeso, JA. Preventing levodopa induced dyskinesia. Ann Neurol 2000; 47 (suppl 1): 167–78.Google Scholar
3Quinn NP. Drug treatment of Parkinson's disease. BMJ 1995; 310: 575–79.CrossRefGoogle Scholar
4Van Camp, G, Flamez, A, Cosyns, B, Goldstein, J, Perdaens, C, Schoors, D. Heart valvular disease in patients with Parkinson's disease treated with high-dose pergolide. Neurology 2003; 61: 859–61.CrossRefGoogle ScholarPubMed
5Frucht, S, Rogers, JD, Greene, PE, Gordon, MF, Fahn, S. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology 1999; 52: 1908.CrossRefGoogle ScholarPubMed
6Ferreira, JJ, Pona, N, Costa, J, Coelho, M, Brefel-Courbon, C, Montastruc, JLet al.Somnolence as an adverse drug reaction of antiparkinsonian drugs: a meta analysis of published randomised controlled trials. Mov Disord 2000; 15 (suppl 3): 128.Google Scholar
7Pal, PK, Calne, S, Samii, A, Fleming, JAE. A review of normal sleep and its disturbances in Parkinson's disease. Parkinsonism Relat Disord 1999; 5: 118.CrossRefGoogle ScholarPubMed
8Rascol, O, Brooks, DJ, Korczyn, AD, De Deyn, PP, Clarke, CE, Lang, AE. A five year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. N Engl J Med 2000; 342: 1484–91.CrossRefGoogle ScholarPubMed
9Parkinson Study Group; Pramipexole versus levodopa as initial treatment for Parkinson's disease. JAMA 2000; 284: 1931–81.CrossRefGoogle Scholar
10Rinne, UK and the PKDS009 Collaborative Study Group. A five year double blind study with cabergoline versus levodopa in the treatment of early Parkinson's disease. Parkinsonism Relat Disord 1999; 5 (suppl): S84.Google Scholar
11Watts, RL, Lyons, K, Pahwa, R, Sethi, K, Stern, M, Hauser, RAet al.Onset of dyskinesia with adjunct ropinirole prolonged-release or additional levodopa in early Parkinson's disease. Mov Disord 2010; 25: 858–66.CrossRefGoogle ScholarPubMed
12Waters, CH, Sethi, KD, Hauser, RA, Molho, E, Bertoni, JM, Zydis Selegiline Study Group. Zydis selegiline reduces off time in Parkinson's disease patients with motor fluctuations: a 3-month, randomized, placebo-controlled study. Mov Disord 2004; 19: 426–32.CrossRefGoogle ScholarPubMed
13Asif, M, Siddiqui, A, Plosker, GL. Rasagiline. Drugs Aging 2005; 22: 8391.Google Scholar
14Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002; 59: 1937–43.CrossRefGoogle Scholar
15Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 2005; 62: 241–48.CrossRefGoogle Scholar
16Rascol, O, Brooks, DJ, Melamed, E, Oertel, W, Poewe, W, Stocchi, F, Tolosa, E; LARGO Study Group. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005; 365: 947–54.CrossRefGoogle ScholarPubMed
17Ives, NJ, Stowe, RL, Marro, J, Counsell, C, Macleod, A, Clarke, CE, Gray, R, Wheatley, K. Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ 2004; 329: 593.CrossRefGoogle ScholarPubMed
18Verhagen Metman, L, Del Dotto, P, van der Munckhof, P, Fang, J, Mouradian, MM, Chase, TN. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease. Neurology 1998; 50: 1323–26.CrossRefGoogle ScholarPubMed
19Metman, LV, Del Dotto, P, LePoole, K, Konitsiotis, S, Fang, J, Chase, TN. Amantadine for levodopa induced dyskinesias: a 1 year follow up study. Arch Neurol 1999; 56: 1383–86.CrossRefGoogle ScholarPubMed
20Luginger, E, Wenning, GK, Bosch, S, Poewe, WH. Beneficial effects of amantadine on levodopa induced dyskinesias in Parkinson's disease. Mov Disord 1998; 13 (suppl 2): 158.Google Scholar
21Nutt, JG, Woodward, WR, Beckner, RM, Stone, CK, Berggren, K, Carter, JH, Gancher, ST, Hammerstad, JP, Gordin, A. Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology 1994; 44: 913–19.CrossRefGoogle ScholarPubMed
22Deane, KH, Spieker, S, Clarke, CE, Deane, KHO, Spieker, S, Clarke, CE. Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease. Cochrane Database Syst Rev 2004; CD004554.Google ScholarPubMed
23Brooks, DJ, Forsyth, D, Playfer, JR, Williams, AC. The role of entacapone in the management of Parkinson's disease. Hospital Med 2000; 61: 267–71.CrossRefGoogle ScholarPubMed
24Stocchi, F, Rascol, O, Kieburtz, K, Poewe, W, Jankovic, J, Tolosa, E, Barone, P, Lang, AE, Olanow, CW. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: The STRIDE-PD study. Ann Neurol 2010; 68: 1827.CrossRefGoogle ScholarPubMed
25Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disablity in early Parkinson's disease. N Eng J Med 1993; 328: 176–83.CrossRefGoogle Scholar
26Whone, AL, Watts, RL, Stoessl, AJ, Davis, M, Reske, S, Nahmias, C, Lang, AE, Rascol, O, Ribeiro, MJ, Remy, P, Poewe, WH, Hauser, RA, Brooks, DJ; REAL-PET Study Group. Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol 2003; 54: 93101.CrossRefGoogle ScholarPubMed
27Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression [see comment]. JAMA 2002; 287: 1653–61.CrossRefGoogle Scholar
28Fahn, S, Oakes, D, Shoulson, I, Kieburtz, K, Rudolph, A, Lang, A, Olanow, CW, Tanner, C, Marek, K; Parkinson Study Group. Levodopa and the progression of Parkinson's disease. N Eng J Med 2004; 351: 2498–508.Google ScholarPubMed
29Olanow, CW, Rascol, O, Hauser, R, Feigin, PD, Jankovic, J, Lang, A, Langston, W, Melamed, E, Poewe, W, Stocchi, F, Tolosa, E; ADAGIO Study Investigators. A double-blind, delayed-start trial of rasagiline in Parkinson's disease. N Engl J Med 2009; 361: 1268–78.CrossRefGoogle ScholarPubMed
30Schapira, AH, Obeso, J. Timing of treatment initiation in Parkinson's disease: a need for reappraisal? Ann Neurol 2006; 59: 559–62.CrossRefGoogle ScholarPubMed
31Gray, R, Patel, S, Ives, N, Rick, Cet al.A large randomised trial assessing quality of life in patients with early PD: results from PD Med early. Parkinsonism Relat Disord 2012; 18 (suppl 2): S32.CrossRefGoogle Scholar
32Koller, W, Lees, A, Doder, M, Hely, M, Tolcapone/Pergolide Study Group. Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson's disease patients with motor fluctuations. Mov Disord 2001; 16: 858–66.CrossRefGoogle ScholarPubMed
33Clarke, CE, Patel, S, Ives, N, Rick, Cet al.A large randomised trial assessing quality of life in patients with early PD: results from PD Med later. Parkinsonism Relat Disord 2012; 18 (suppl 2): S33.CrossRefGoogle Scholar
34Lundqvist, C, Nystedt, T, Reiertsen, O, Grotli, R, Beiske, AG. Continuous treatment with levodopa of Parkinson disease. Tidsskrift for Den Norske Laegeforening 2005; 125: 2638–40.Google ScholarPubMed
35Frankel, JP, Lees, AJ, Kempster, PA, Stern, GM. Subcutaneous apomorphine in the treatment of Parkinson's disease. J Neurol Neurosurg Psychiatry 1990; 53: 96101.CrossRefGoogle ScholarPubMed
36MacMahon DG. Use of apomorphine in clinical practice. In Stern, GM (ed), Advances in Neurology, vol 80. Philadelphia: Lippincott Williams and Wilkins, 1999: pp. 529–33.Google Scholar
37Colzi, A, Turner, K, Lees, AJ. Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesia in Parkinson's disease. J Neurol Neurosurg Psychiatry 1998; 64: 573–76.CrossRefGoogle Scholar
38Wenning, GK, Bosch, S, Luginger, E, Poewe, WH. Effects of long term, continuous subcutaneous apomorphine infusions on motor complications in advanced Parkinson's disease. In Stern, GM (ed), Advances in Neurology. Philadelphia: Lippincott Williams and Wilkins, 1999: pp. 545–48.Google Scholar
39Obeso, JA, Guridi, J, DeLong, M. Surgery for Parkinson's disease. J Neurol Neurosurg Psychiatry 1997; 62: 28.CrossRefGoogle ScholarPubMed
40Bronstein, J, Tagliate, M, Alterman, R. Deep brain stimulation for Parkinson's disease. An expert consensus and review of key issues. Arch Neurol 2011; 68: 165–71.CrossRefGoogle ScholarPubMed
41Burn, DJ, Troster, A. Neuropsychiatric complications of medical and surgical therapies for Parkinson's disease. J Geriat Psychiatry Neurol 2004; 17: 172–80.CrossRefGoogle ScholarPubMed
42Schüpbach, M, Gargiulo, M, Welter, ML, Mallet, L, Béhar, C, Houeto, JL, Maltête, D, Mesnage, V, Agid, Y. Neurosurgery in Parkinson's disease: a distressed mind in a repaired body? Neurology 2006; 66: 1811–16.CrossRefGoogle Scholar
43Parsons, T, Rogers, S, Braaten, A, Woods, S, Troster, A. Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a meta-analysis. Lancet Neurol 2006; 5: 578–88.CrossRefGoogle ScholarPubMed
44Freund, H. Long term effects of deep brain stimulation in Parkinson's disease. Brain 2005; 128: 2222–23.CrossRefGoogle ScholarPubMed
45Montgomery, EB, Gale, J. Mechanisms of action of deep brain stimulation (DBS). Neurosci Biobehav Rev 2008; 32: 388407.CrossRefGoogle ScholarPubMed
46Follett, KA, Weaver, FM, Stern, M, Hur, K, Harris, CL, Luo, P, Marks, WJ Jr, Rothlind, J, Sagher, O, Moy, C, Pahwa, R, Burchiel, K, Hogarth, P, Lai, EC, Duda, JE, Holloway, K, Samii, A, Horn, S, Bronstein, JM, Stoner, G, Starr, PA, Simpson, R, Baltuch, G, De Salles, A, Huang, GD, Reda, DJ; CSP 468 Study Group. Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease. N Engl J Med 2010; 362: 2077–91.CrossRefGoogle ScholarPubMed
47Saint-Cyr, J, Trepannier, L, Kumar, R, Lozano, A, Lang, AE. Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. Brain 2000; 123: 2091–108.CrossRefGoogle ScholarPubMed
48Williams, A, Gill, S, Varma, T, Jenkinson, C, Quinn, N, Mitchell, R, Scott, R, Ives, N, Rick, C, Daniels, J, Patel, S, Wheatley, K; PD SURG Collaborative Group. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial. Lancet Neurology 2010; 9: 581–91.CrossRefGoogle Scholar
49Krack, P, Hamel, W, Mehdorn, HM, Deuschl, G. Surgical treatment of Parkinson's disease. Curr Opin Neurol 1999; 12: 417–25.CrossRefGoogle ScholarPubMed
50Weaver, F, Follet, K, Stern, M. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson's disease. A randomized controlled trial. JAMA 2009; 310: 6373.CrossRefGoogle Scholar
51Lang, AE, Lozano, AE. Parkinson's disease: second of two parts. N Engl J Med 1998; 339: 1130–43.CrossRefGoogle ScholarPubMed
52Freed, CR, Greene, PE, Breeze, RE, Tsai, WY, DuMouchel, W, Kao, R, Dillon, S, Winfield, H, Culver, S, Trojanowski, JQ, Eidelberg, D, Fahn, S. Transplantation of embryonic dopamine neurones for severe Parkinson's disease. N Eng J Med 2001; 344: 710–19.CrossRefGoogle ScholarPubMed
53Olanow, CW, Goetz, CG, Kordower, JH, Stoessl, AJ, Sossi, V, Brin, MF, Shannon, KM, Nauert, GM, Perl, DP, Godbold, J, Freeman, TB. A double blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol 2003; 54: 403–14.CrossRefGoogle ScholarPubMed
54Lang, AE, Obeso, JA. Challenges in Parkinson's disease: restoration of the nigrostriatal dopamine system is not enough. Lancet Neurology 2004; 3: 309–16.CrossRefGoogle ScholarPubMed
55LeWitt, PA, Rezai, AR, Leehey, MA, Ojemann, SG, Flaherty, AW, Eskandar, EN, Kostyk, SK, Thomas, K, Sarkar, A, Siddiqui, MS, Tatter, SB, Schwalb, JM, Poston, KL, Henderson, JM, Kurlan, RM, Richard, IH, Van Meter, L, Sapan, CV, During, MJ, Kaplitt, MG, Feigin, A. AAV2-GAD gene therapy for advanced Parkinson's disease: a double blind sham surgery controlled study. Lancet Neurol 2011; 10: 309–19.CrossRefGoogle Scholar
56Chaudhuri, KR, Healy, D, Schapira, A. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 2006; 5: 235–45.CrossRefGoogle ScholarPubMed
57Hely, MA, Reid, WGJ, Trafficante, R. The Sydney multicentre study of Parkinson's disease: Non L-dopa responsive symptoms dominate at 15 years. Mov Disord 2005; 20: 190–99.CrossRefGoogle Scholar
58Hely, MA, Reid, WGJ, Adena, MA, Halliday, G, Morris, J. The Sydney multicenter study of Parkinson's disease: the inevitability 0f dementia at 20 years. Mov Disord 2008; 23: 837–44.CrossRefGoogle Scholar
59Martinez-Martin, P, Schapira, AH, Stocchi, F, Sethi, K, Odin, P, MacPhee, G, Brown, RG, Naidu, Y, Clayton, L, Abe, K, Tsuboi, Y, MacMahon, D, Barone, P, Rabey, M, Bonuccelli, U, Forbes, A, Breen, K, Tluk, S, Olanow, CW, Thomas, S, Rye, D, Hand, A, Williams, AJ, Ondo, W, Chaudhuri, KR. Prevalence of non-motor symptoms in Parkinson's disease in an international setting; study using Non-motor Symptoms Questionnaire in 545 patients. Mov Disord 2007; 22: 1623–29.CrossRefGoogle Scholar
60Barone, P, Antonini, A, Colosimo, C, Marconi, R, Morgante, L, Avarello, TP, Bottacchi, E, Cannas, A, Ceravolo, G, Ceravolo, R, Cicarelli, G, Gaglio, RM, Giglia, RM, Iemolo, F, Manfredi, M, Meco, G, Nicoletti, A, Pederzoli, M, Petrone, A, Pisani, A, Pontieri, FE, Quatrale, R, Ramat, S, Scala, R, Volpe, G, Zappulla, S, Bentivoglio, AR, Stocchi, F, Trianni, G, Dotto, PD; PRIAMO study group. The Priamo Study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord 2009; 24: 1641–49.CrossRefGoogle ScholarPubMed
61Chaudhuri, KR, Schapira, AHV. Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment. Lancet Neurol 2009; 8: 464–74.CrossRefGoogle ScholarPubMed
62Macphee, GJA, MacMahon, DG. Non motor symptoms and comorbidity in Parkinson's disease. In Chaudhuri, KR, Tolosa, E, Schapira, A, Powe, W (eds), Non Motoor Symptoms of Parkinson's Disease. Oxford University Press, 2009.Google Scholar
63Shulman, L, Taback, R, Rabinstein, A, Weiner, WJ. Non-recognition of depression and other non-motor symptoms in Parkinson's disease. Parkinsonism Relat Disord 2002; 8: 193–97.CrossRefGoogle ScholarPubMed
64Chaudhuri, KR, Prieto-Jurcynska, C, Naidu, Y, Mitra, T, Frades-Payo, B, Tluk, S. The non-declaration of non-motor symptoms of Parkinson's disease to health care professionals: an international study using the Nonmotor Symptoms Questionnaire. Mov Disord 2010; 25: 704–9.CrossRefGoogle Scholar
65Chaudhuri, KR, Martinez-Martin, P, Schapira, AH, Stocchi, F, Sethi, K, Odin, P, Brown, RG, Koller, W, Barone, P, MacPhee, G, Kelly, L, Rabey, M, MacMahon, D, Thomas, S, Ondo, W, Rye, D, Forbes, A, Tluk, S, Dhawan, V, Bowron, A, Williams, AJ, Olanow, CW. An international multicentre pilot of the first comprehensive self-completed non-motor symptoms questionnaire for Parkinson's disease: the NMSQuest study. Mov Disord 2006; 21:916923.CrossRefGoogle Scholar
66Movement Disorder Society Task force on Rating Scales for Parkinson's disease. The Unified Parkinson's disease rating scale (UPDRS): status and recommendations. Mov Disord 2003; 18: 738–50.CrossRefGoogle Scholar
67Goetz, CG, Tilley, BC, Shaftman, SR, Stebbins, GT, Fahn, S, Martinez-Martin, P, Poewe, W, Sampaio, C, Stern, MB, Dodel, R, Dubois, B, Holloway, R, Jankovic, J, Kulisevsky, J, Lang, AE, Lees, A, Leurgans, S, LeWitt, PA, Nyenhuis, D, Olanow, CW, Rascol, O, Schrag, A, Teresi, JA, van Hilten, JJ, LaPelle, N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Scale, presentation and clinimetric testing results. Mov Disord 2008; 23: 2129–70.CrossRefGoogle ScholarPubMed
69Grosset, DG, Macphee, GJA, Nairn, M. Diagnosis and pharmacological management of Parkinson's disease: summary of SIGN guidelines. BMJ 2010; 340: 5614.CrossRefGoogle ScholarPubMed
70Zesiewicz, TA, Sullivan, KL, Arnulf, I, Chaudhuri, KR, Morgan, JC, Gronseth, GS, Miyasaki, J, Iverson, DJ, Weiner, WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter. Treatment of nonmotor symptoms of Parkinson's disease: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010; 74: 924–31.CrossRefGoogle Scholar
71Miyasaki, JM, Shannon, K, Voon, V, Ravina, B, Kleiner-Fisman, G, Anderson, K. Practice Parameter. Evaluation of treatment of depression, psychosis and dementia in Parkinson's disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 66: 9961002.CrossRefGoogle Scholar
72Dalrymple-Alford, JC, Livingston, L, MacAskill, MR, Graham, C, Melzer, TR, Porter, RJ, Watts, R, Anderson, TJ. Characterising mild cognitive impairment in Parkinson's disease. Mov Disord 2011; 26: 629–36.CrossRefGoogle ScholarPubMed
73Aarsland, D, Marsh, L, Shrag, A. Neuropsychiatric symptoms in Parkinson's disease. Mov Disord 2009; 24: 2175–86.CrossRefGoogle ScholarPubMed
74Aarsland, D, Kurz, M. The epidemiology of dementia associated with Parkinson's disease. J Neurol Sci 2010; 289: 1822.CrossRefGoogle Scholar
75Ebmeier, KP, Calder, SA, Crawford, JR, Stewart, L, Besson, JAO, Mutch, W. Clinical features predicting dementia in idiopathic Parkinson's disease. Neurology 1990; 40: 1222–24.CrossRefGoogle ScholarPubMed
76Stern, Y, Marder, K, Tang, M-X, Mayeux, R. Antecedent clinical features associated with dementia in Parkinson's disease. Neurology 1993; 43: 1690–92.CrossRefGoogle ScholarPubMed
77Biggins, CA, Boyd, JL, Harrop, FM, Madely, P, Mindham, RHS, Randall, JI, Spokes, EG. A controlled longitudinal study of dementia in Parkinson's disease. J Neurol Neurosurg Psychiatry 1992; 55: 566–71.CrossRefGoogle ScholarPubMed
78Williams-Gray, C, Evans, J, Goris, A, Foltynie, T, Ban, M, Robbins, T. The distinct cognitive syndromes of Parkinson's disease: a five year follow-up of the CamPaIGN cohort. Brain 2009; 132: 2958–69.CrossRefGoogle Scholar
79Hurtig, HI, Trojanowski, JQ, Galvin, J, Ewbank, D, Schmidt, ML, Lee, VM, Clark, CM, Glosser, G, Stern, MB, Gollomp, SM, Arnold, SE. Alpha synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease. Neurology 2000; 54: 1916–21.CrossRefGoogle ScholarPubMed
80Colosimo, C, Hughes, AJ, Killard, L, Lees, AJ. Lewy body cortical involvement may not always predict dementia in Parkinson's disease. J Neurol Neurosurg Psychiatry 2003; 74: 852–56.CrossRefGoogle Scholar
81Jellinger, KA. The Neuropathologic Diagnosis of Secondary Parkinsonian Syndromes. In Battistin, L, Scarlato, G, Caraceni, T, Ruggieri, S (eds), Advances in Neurology. Philadelphia: Lippincott-Raven, 1996, pp. 293303.Google Scholar
82Emre, M, Aarsland, D, Brown, R, Burn, DJ. Clinical and diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord 2007; 22: 1689–707.CrossRefGoogle ScholarPubMed
83Dubois, B, Burn, D, Goetz, C, Aarsland, D, Brown, RG, Broe, GA, Dickson, D, Duyckaerts, C, Cummings, J, Gauthier, S, Korczyn, A, Lees, A, Levy, R, Litvan, I, Mizuno, Y, McKeith, IG, Olanow, CW, Poewe, W, Sampaio, C, Tolosa, E, Emre, M. Diagnostic procedures for Parkinson's disease dementia: recommendations form the Movement Disorders Society task force. Mov Disord 2007; 22: 2314–24.CrossRefGoogle Scholar
84Zadikoff, C, Fox, SH, Tang-Wai, DF, Thomsen, T, de Bie, RM, Wadia, P, Miyasaki, J, Duff-Canning, S, Lang, AE, Marras, C. A comparison of the Mini Mental State Exam to the Montreal Cognitive Assessment in identifying cognitive deficits in Parkinson's disease. Mov Disord 2008; 23: 297–99.CrossRefGoogle Scholar
85Burn, D, Emre, M, McKeith, I, De Deyn, PP, Aarsland, D, Hsu, C, Lane, R. Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. Mov Disord 2006; 21: 1899–907.CrossRefGoogle ScholarPubMed
86Emre, M, Aarsland, D, Albanese, A, Byrne, EJ, Deuschl, G, De Deyn, PP, Durif, F, Kulisevsky, J, van Laar, T, Lees, A, Poewe, W, Robillard, A, Rosa, MM, Wolters, E, Quarg, P, Tekin, S, Lane, R. Rivastigmine for dementia associated with Parkinson's disease. N Engl J Med 2004; 351: 2509–18.CrossRefGoogle ScholarPubMed
87Leroi, I, Brandt, J, Reich, S, Lykestos, C. Randomised placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease. Int J Ger Psychiatry 2004; 19: 18.CrossRefGoogle ScholarPubMed
88Aarsland, D, Ballard, C, Walker, Z, Bostrom, F, Alves, G, Kossakowski, K, Leroi, I, Pozo-Rodriguez, F, Minthon, L, Londos, E. Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double blind multicenter trial. Lancet Neurology 2009; 8: 613–18.CrossRefGoogle ScholarPubMed
89Chaudhuri, KR. Nocturnal symptom complex in PD and its management. Neurology 2003; 61 (suppl 3): S1723.CrossRefGoogle ScholarPubMed
90Postuma, RB, Lang, AE, Massicotte-Marquez, J, Montplaisir, J. Potential early markers of Parkinson's disease in idiopathic REM sleep behaviour disorder. Neurology 2006; 66: 845–51.CrossRefGoogle Scholar
91Arnulf, I. Excessive daytime sleepiness in Parkinsonism. Sleep Med Rev 2005; 9: 185200.CrossRefGoogle ScholarPubMed
92Arnulf, I, Konofal, E, Merino-Andreu, M, Houeto, JL, Mesnage, V, Welter, ML, Lacomblez, L, Golmard, JL, Derenne, JP, Agid, Y. Parkinson's disease and sleepiness: an integral part of PD. Neurology 2002; 58: 1019–24.CrossRefGoogle ScholarPubMed
93Ondo, WG, Fayle, R, Atassi, F, Jankovic, J. Modafinil for daytime somnolence in Parkinson's disease: double blind placebo controlled parallel trial. J Neurol Neurosurg Psychiatry 2005; 76: 1636–39.CrossRefGoogle ScholarPubMed
94Cummings, JL. Depression and Parkinson's disease: a review. Am J Psychiatry 1992; 4: 443–54.Google Scholar
95Weintraub, D, Stern, M. Psychiatric complications in Parkinson's disease. Am J Geriat Psychiatry 2005; 13: 844–51.CrossRefGoogle Scholar
96Reijnders, J, Ehrt, U, Weber, W, Aarsland, D, Leentjens, A. A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord 2008; 23: 183–89.CrossRefGoogle ScholarPubMed
97Allain, H, Schuck, S, Mauduit, N. Depression in Parkinson's disease. BMJ 2000; 320: 1287–88.CrossRefGoogle ScholarPubMed
98Meara, J, Mitchelmore, E, Hobson, P. Use of the GDS-15 geriatric depression scale as a screening instrument for depressive symptomatology in patients with Parkinson's disease and their carers in the community. Age Ageing 1999; 28: 3538.CrossRefGoogle ScholarPubMed
99Marsh, L, McDonald, W, Cummings, JL, Ravina, P. Provisional diagnosis criteria for depression in Parkinson's disease: report of an NINDS/NIMH Work Group. Mov Disord 2006; 21: 148–58.CrossRefGoogle ScholarPubMed
100Burn, DJ. Beyond the iron mask: towards better recognition and treatment of depression associated with Parkinson's disease. Mov Disord 2002; 17: 445–54.CrossRefGoogle ScholarPubMed
101Rektorová, I, Rektor, I, Bares, M, Dostál, V, Ehler, E, Fanfrdlová, Z, Fiedler, J, Klajblová, H, Kulist’ák, P, Ressner, P, Svátová, J, Urbánek, K, Velísková, J. Pramipexole and pergolide in the treatment of depression in Parkinson's disease. Eur J Neurol 2003; 10: 399406.CrossRefGoogle ScholarPubMed
102Barone, P, Poewe, W, Albrecht, S, Debieuvre, C, Massey, D, Rascol, O, Tolosa, E, Weintraub, D. Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised double-blind placebo controlled trial. Lancet Neurol 2010; 9: 573–80.CrossRefGoogle ScholarPubMed
103Devos, D, Dujardin, K, Poirot, I, Moreau, C, Cottencin, O, Thomas, P, Destée, A, Bordet, R, Defebvre, L. Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double blind, randomised, placebo controlled trial. Mov Disord 2008; 23: 850–57.CrossRefGoogle Scholar
104Miyasaki, JM, Shannon, K, Voon, V, Ravina, B, Kleiner-Fisman, G, Anderson, K. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson's disease (an evidence based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 66: 9961002.CrossRefGoogle Scholar
105Lieberman, A. Depression in Parkinson's disease. Acta Neurol Scand 2006; 113: 18.CrossRefGoogle ScholarPubMed
106Richard, IH, Kurlan, R, Factor, SA. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Neurology 1997; 48: 1070–77.CrossRefGoogle Scholar
107Wolters, EC. Dopaminomimetic psychosis in Parkinson's disease patients: diagnosis. Neurology 1999; 52 (suppl 3): S1013.Google ScholarPubMed
108Goetz, CG, Wenging, F, Leurgans, S, Bernard, B, Stebbins, GT. The malignant course of ‘Benign hallucinations’ in Parkinson's disease. Arch Neurol 2006; 63: 235–38.CrossRefGoogle Scholar
109Goetz, CG, Tanner, CM, Klawans, HL. Pharmacology of hallucinations induced by long term drug therapy. Am J Psychiat 1982; 139: 494–97.Google ScholarPubMed
110Goetz, CG, Stebbins, GT. Risk factors for nursing home placement in advanced Parkinson's disease. Neurology 1993; 43: 2227–29.CrossRefGoogle ScholarPubMed
111Goetz, CG, Stebbins, GT. Mortality and hallucination in nursing home patients with advanced Parkinson's disease. Neurology 1995; 45: 669–71.CrossRefGoogle ScholarPubMed
112Goetz, CG, Vogel, C, Tanner, CM, Stebbins, GT. Early dopaminergic drug induced hallucinations in parkinsonian patients. Neurology 1998; 51: 811–14.CrossRefGoogle ScholarPubMed
113Tanner, CM, Vogel, C, Goetz, CG, Klawans, HL. Hallucinations in Parkinson's disease: a population study. Ann Neurol 1983; 14: 136.Google Scholar
114Sanchez-Ramos, JR, Ortoll, R, Paulson, GW. Visual hallucinations associated with Parkinson's disease. Arch Neurol 1996; 53: 1265–68.CrossRefGoogle Scholar
115Forsaa, E, Larsen, J-P, Wentzel-Larsen, T, Goetz, CG, Stebbins, GT, Aarsland, D, Alves, G. A 12 year based prospective study of psychosis in Parkinson's disease. Arch Neurol 2010; 667: 9961001.Google Scholar
116Graham, JM, Grunewald, RA, Sagar, HJ. Hallucinosis in idiopathic Parkinson's disease. J Neurol Neurosurg Psychiat 1997; 63: 434–40.CrossRefGoogle ScholarPubMed
117Merims, D, Shabtai, H, Korczyn, AD, Peretz, C, Weizman, N, Giladi, N. Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease. J Neural Transm 2004; 111: 1447–53.CrossRefGoogle Scholar
118Friedman, JH, Factor, SA. Atypical antipsychotics in the treatment of drug induced psychosis in Parkinson's disease. Mov Disord 2000; 15: 201–11.3.0.CO;2-D>CrossRefGoogle ScholarPubMed
119Kipps, C, Fung, V, Grattan-Smith, P, de Moore, G, Morris, J. Movement disorder emergencies. Mov Disord 2005; 20: 322–34.CrossRefGoogle ScholarPubMed
120Merims, D, Balas, M, Peretz, C, Shabtai, H, Giladi, N. Rater blinded, prospective comparison: Quetiapine versus Clozapine for Parkinson's Disease psychosis. Clin Neuropharmacol 2006; 29: 331–37.CrossRefGoogle ScholarPubMed
121Grosset, KA, Macphee, G, Pal, G, Stewart, D, Watt, A, Davie, J, Grosset, DG. Problematic gambling on dopamine agonists: not such a rarity. Mov Disord 2006; 21: 2206–8.CrossRefGoogle Scholar
122MacMahon, DG, Macphee, GJA. Dopamine agonists and impulse control disorders in Parkinson's disease. Prog Neurol 2008; 12: 59.Google Scholar
123Weintraub, D, Koester, J, Potenza, M, Siderowf, A, Stacy, M, Voon, V. Impulse control disorders in Parkinson's disease: a cross-sectional study. Arch Neurol 2010; 67: 589–95.CrossRefGoogle ScholarPubMed
124Mamikonyan, E, Siderowf, AD, Duda, JE, Potenza, MN, Horn, S, Stern, MB, Weintraub, D. Long-term follow-up of impulse control disorders in Parkinson's disease. Mov Disord 2008; 23: 7580.CrossRefGoogle ScholarPubMed
125Macphee, GJA, Copeland, C, Stewart, D, Grosset, K, Grosset, DG. Clinical follow up of pathological gambling in Parkinson's disease in the West of Scotland study. Mov Disord 2009; 24: 2430–31.CrossRefGoogle Scholar
126Evans, A, Lees, AJ. Dopamine dysregulation syndrome in Parkinson's disease. Curr Opin Neurol 2004; 17: 393–98.CrossRefGoogle ScholarPubMed
127Chaudhuri, KR. Autonomic dysfunction in Parkinson's disease. Curr Opin Neurol 2001; 14: 505–11.CrossRefGoogle Scholar
128Allcock, L. Orthostatic hypotension in Parkinson's disease. ACNR 2012; 10: 5152.Google Scholar
129Schoffer, K, Henderson, R, O'Maley, K, O'Sullivan, J. Non-pharmaccological treatment, fludrocortisone and domperidone for orthostatic hypotension in Parkinson's disease. Mov Disord 2007; 22: 1543–49.CrossRefGoogle ScholarPubMed
130Stocchi, F. Gastointestinal dysfunctions in Parkinson's disease. In Chaudhuri, KR, Schapira, A, Tolosa, E, Poewe, W (eds), Non Motor Symptoms of Parkinson's Disease. Oxford: Oxford University Press, 2009.Google Scholar
131Zangaglia, R, Martignoni, E, Glorioso, M, Ossola, M, Riboldazzi, G, Calandrella, D, Brunetti, G, Pacchetti, C. Macrogol for the treatment of constipation in Parkinson's disease: a randomized placebo-controlled study. Mov Disord 2007; 22: 1239–44.CrossRefGoogle ScholarPubMed
132Ford, B. Pain in Parkinson's disease. Clin Neurosci 1998; 5: 6372.Google ScholarPubMed
133Ford, B. Pain in Parkinson's disease. Mov Disord 2010; 25: 98103.CrossRefGoogle ScholarPubMed