Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000004.xml
Download PDF
Aktuelle Neurologie 2013; 40(08): 452-461
DOI: 10.1055/s-0033-1355379
DOI: 10.1055/s-0033-1355379
Übersicht
Prodromale Marker der Parkinson-Krankheit
Prodromal Markers of Parkinson’s DiseaseFurther Information
Publication History
Publication Date:
07 October 2013 (online)
Zusammenfassung
Die Parkinson-Krankheit (PK) ist die zweithäufigste neurodegenerative Erkrankung des älteren Menschen. Sie ist definiert durch die Kardinalsymptome Akinese, Rigor und Ruhetremor. Neben diesen motorischen Symptomen treten aber auch nichtmotorische Symptome wie Depression, Hyposmie, autonome Störungen und spezifische Schlafstörungen auf. Viele PK-Patienten leiden schon vor dem Zeitpunkt der neurologischen Diagnosestellung unter nichtmotorischen Symptomen. Diese Prodromalphase kann unterschiedlich lang sein. Nach bisherigen Studien erreicht als prodromale Marker die höchste Sensitivität die Hyposmie gefolgt von autonomer Dysfunktion (Obstipation), eine hohe Spezifität wird durch die REM-Schlaf-Verhaltensstörung erreicht. Mit dieser Ausnahme sind die Spezifitäten aller bisherigen klinischen prodromalen Marker gering. Sogenannte Biomarker, die das Auftreten der motorischer PK-Symptome voraussagen, sind in der klinischen Routine bisher nicht etabliert. Neue Marker oder die Kombination von verschiedenen Markern könnten möglicherweise eine bessere prognostische Aussage ermöglichen, und insbesondere bei der Identifizierung von geeigneten Patienten für krankheitsmodifizierende Therapiestudien hilfreich sein.
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease in the elderly. It is characterised by the cardinal symptoms akinesia, rigidity and rest tremor. Besides these motor symptoms there are also non-motor signs like depression, hyposmia, autonomic dysfunction and specific sleep disorders. Many PD patients suffer from non-motor symptoms before the time of the neurological diagnosis. This prodromal phase can vary in duration. According to existing studies the highest sensitivity as prodromal marker is reached by hyposmia followed by autonomic dysfunction (constipation). Except for REM sleep behaviour disorder, the specificities for all current clinical markers are low. So-called biomarkers that predict the manifestation of motor symptoms of PD are not yet established in clinical routine. New markers or the combination of different markers may allow a better prognostic statement and, especially, may be helpful in the identification of appropriate patients for disease-modifying therapeutical studies.
-
Literatur
- 1 Gaenslen A, Swid I, Liepelt-Scarfone I et al. The patients’ perception of prodromal symptoms before the initial diagnosis of Parkinson’s disease. Mov Disord 2011; 26: 653-658
- 2 Braak H, Del Tredici K, Rüb U et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24: 197-211
- 3 Wakabayashi K, Takahashi H, Takeda S et al. Parkinson’s disease: the presence of Lewy bodies in Auerbach’s and Meissner’s plexuses. Acta Neuropathol 1988; 76: 217-221
- 4 Wakabayashi K, Takahashi H, Ohama E et al. Parkinson’s disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system. Acta Neuropathol 1990; 79: 581-583
- 5 Wakabayashi K, Takahashi H. The intermediolateral nucleus and Clarke’s column in Parkinson’s disease. Acta Neuropathol 1997; 94: 287-289
- 6 Schulz-Schaeffer WJ. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia. Acta Neuropathol 2010; 120: 131-143
- 7 Doty RL, Stern MB, Pfeiffer C et al. Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 1992; 55: 138-142
- 8 Hawkes CH, Shephard BC, Daniel SE. Olfactory dysfunction in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997; 62: 436-446
- 9 Haehner A, Boesveldt S, Berendse HW et al. Prevalence of smell loss in Parkinson’s disease – a multicenter study. Parkinsonism Relat Disord 2009; 15: 490-494
- 10 Doty RL, Deems DA, Stellar S. Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 1988; 38: 1237-1244
- 11 Iranzo A, Serradell M, Vilaseca I et al. Longitudinal assessment of olfactory function in idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord 2013; 19: 600-604
- 12 Deeb J, Shah M, Muhammed N et al. A basic smell test is as sensitive as a dopamine transporter scan: comparison of olfaction, taste and DaTSCAN in the diagnosis of Parkinson’s disease. QJM 2010; 103: 941-952
- 13 Hawkes CH. Parkinson’s disease and aging: same or different process?. Mov Disord 2008; 23: 47-53
- 14 Shah M, Muhammed N, Findley LJ et al. Olfactory tests in the diagnosis of essential tremor. Parkinsonism Relat Disord 2008; 14: 563-568
- 15 Olichney JM, Murphy C, Hofstetter CR et al. Anosmia is very common in the Lewy body variant of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2005; 76: 1342-1347
- 16 Hawkes C. Olfaction in neurodegenerative disorder. Mov Disord 2003; 18: 364-372
- 17 Krüger S, Haehner A, Thiem C et al. Neuroleptic-induced parkinsonism is associated with olfactory dysfunction. J Neurol 2008; 255: 1574-1579
- 18 Silveira-Moriyama L, Schwingenschuh P, O’Donnell A. Olfaction in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDDs). J Neurol Neurosurg Psychiatry 2009; 80: 744-748
- 19 Silveira-Moriyama L, Hughes G, Church A et al. Hyposmia in progressive supranuclear palsy. Mov Disord 2010; 25: 570-577
- 20 Alcalay RN, Siderowf A, Ottman R et al. Olfaction in Parkin heterozygotes and compound heterozygotes: the CORE-PD study. Neurology 2011; 76: 319-326
- 21 Ferraris A, Ialongo T, Passali GC et al. Olfactory dysfunction in Parkinsonism caused by PINK1 mutations. Mov Disord 2009; 24: 2350-2357
- 22 Silveira-Moriyama L, Munhoz RP, de Carvalho JM et al. Olfactory heterogeneity in LRRK2 related Parkinsonism. Mov Disord 2010; 25: 2879-2883
- 23 Postuma RB, Gagnon JF, Montplaisir J. Clinical prediction of Parkinson’s disease: planning for the age of neuroprotection. J Neurol Neurosurg Psychiatry 2010; 81: 1008-1013
- 24 Postuma RB, Montplaisir J. Transcranial ultrasound and olfaction in REM sleep behavior disorder: testing predictors of Parkinson’s disease. Sleep Med 2010; 11: 339-340
- 25 Postuma RB, Gagnon JF, Vendette M et al. Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol 2011; 69: 811-818
- 26 Ramjit AL, Sedig L, Leibner J et al. The relationship between anosmia, constipation, and orthostasis and Parkinson’s disease duration: results of a pilot study. Int J Neurosci 2010; 120: 67-70
- 27 Stiasny-Kolster K, Doerr Y, Möller JC et al. Combination of ‘idiopathic’ REM sleep
behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy
demonstrated by dopamine transporter FP-CIT-SPECT. Brain 2005; 128: 126-137
MissingFormLabel
- 28 Bohnen NI, Müller ML, Kotagal V et al. Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson’s disease. Brain 2010; 133: 1747-1754
- 29 Iijima M, Osawa M, Momose M et al. Cardiac sympathetic degeneration correlates with olfactory function in Parkinson’s disease. Mov Disord 2010; 25: 1143-1149
- 30 Lee PH, Yeo SH, Kim HJ et al. Correlation between cardiac 123I-MIBG and odor identification in patients with Parkinson’s disease and multiple system atrophy. Mov Disord 2006; 21: 1975-1977
- 31 Spiegel J, Hellwig D, Möllers MO et al. Transcranial sonography and [123I]FP-CIT SPECT disclose complementary aspects of Parkinson’s disease. Brain 2006; 129: 1188-1193
- 32 Hawkes CH. The prodromal phase of sporadic Parkinson’s disease: does it exist and if so how long is it?. Mov Disord 2008; 23: 1799-1807
- 33 Ross GW, Abbott RD, Petrovitch H et al. Association of olfactory dysfunction with incidental Lewy bodies. Mov Disord 2006; 21: 2062-2067
- 34 Ross GW, Petrovitch H, Abbott RD et al. Association of olfactory dysfunction with risk for future Parkinson’s disease. Ann Neurol 2008; 63: 167-173
- 35 Ponsen MM, Stoffers D, Booij J et al. Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 2004; 56: 173-181
- 36 Sommer U, Hummel T, Cormann K et al. Detection of presymptomatic Parkinson’s disease: combining smell tests, transcranial sonography, and SPECT. Mov Disord 2004; 19: 1196-1202
- 37 Doty RL, Applebaum S, Zusho H et al. Sex differences in odor identification ability: a cross-cultural analysis. Neuropsychologia 1985; 23: 667-672
- 38 Jones RE, Brown CC, Ship JA. Odor identification in young and elderly African-Americans and Caucasians. Spec Care Dentist 1995; 15: 138-143
- 39 Wolfensberger M, Schnieper I, Welge-Lüssen A. Sniffin’Sticks: a new olfactory test battery. Acta Otolaryngol 2000; 120: 303-306
- 40 Archibald NK, Clarke MP, Mosimann UP et al. The retina in Parkinson’s disease. Brain 2009; 132: 1128-1145
- 41 Blekher T, Weaver M, Rupp J et al. Multiple step pattern as a biomarker in Parkinson disease. Parkinsonism Relat Disord 2009; 15: 506-510
- 42 Archibald NK, Clarke MP, Mosimann UP et al. Retinal thickness in Parkinson’s disease. Parkinsonism Relat Disord 2011; 17: 431-436
- 43 Aaker GD, Myung JS, Ehrlich JR et al. Detection of retinal changes in Parkinson’s disease with spectral-domain optical coherence tomography. Clin Ophthalmol 2010; 4: 1427-1432
- 44 Altintaş O, Işeri P, Ozkan B et al. Correlation between retinal morphological and functional findings and clinical severity in Parkinson’s disease. Doc Ophthalmol 2008; 116: 137-146
- 45 Hajee ME, March WF, Lazzaro DR et al. Inner retinal layer thinning in Parkinson disease. Arch Ophthalmol 2009; 127: 737-741
- 46 Inzelberg R, Ramirez JA, Nisipeanu P et al. Retinal nerve fiber layer thinning in Parkinson disease. Vision Res 2004; 44: 2793-2797
- 47 Moschos MM, Tagaris G, Markopoulos I et al. Morphologic changes and functional retinal impairment in patients with Parkinson disease without visual loss. Eur J Ophthalmol 2011; 21: 24-29
- 48 Orimo S, Takahashi A, Uchihara T et al. Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson’s disease. Brain Pathol 2007; 17: 24-30
- 49 Mitsui J, Saito Y, Momose T et al. Pathology of the sympathetic nervous system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylguanidine (MIBG) scintigraphy in a patient with Parkinson disease. J Neurol Sci 2006; 243: 101-104
- 50 Oka H, Toyoda C, Yogo M et al. Cardiovascular dysautonomia in de novo Parkinson’s disease without orthostatic hypotension. Eur J Neurol 2011; 18: 286-292
- 51 Spiegel J, Hellwig D, Farmakis G et al. Myocardial sympathetic degeneration correlates with clinical phenotype of Parkinson’s disease. Mov Disord 2007; 22: 1004-1008
- 52 Valappil RA, Black JE, Broderick MJ et al. Exploring the electrocardiogram as a potential tool to screen for premotor Parkinson’s disease. Mov Disord 2010; 25: 2296-2303
- 53 Postuma RB, Montplaisir J, Lanfranchi P et al. Cardiac autonomic denervation in Parkinson’s disease is linked to REM sleep behavior disorder. Mov Disord 2011; 26: 1529-1533
- 54 Friedrich C, Rüdiger H, Schmidt C et al. Baroreflex sensitivity and power spectral analysis in different extrapyramidal syndromes. J Neural Transm 2008; 115: 1527-1536
- 55 Abbott RD, Petrovitch H, White LR et al. Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 2001; 57: 456-462
- 56 Savica R, Carlin JM, Grossardt BR et al. Medical records documentation of constipation preceding Parkinson disease: A case-control study. Neurology 2009; 73: 1752-1758
- 57 Djaldetti R, Baron J, Ziv I et al. Gastric emptying in Parkinson’s disease: patients with and without response fluctuations. Neurology 1996; 46: 1051-1054
- 58 Goetze O, Nikodem AB, Wiezcorek J et al. Predictors of gastric emptying in Parkinson’s disease. Neurogastroenterol Motil 2006; 18: 369-375
- 59 Hardoff R, Sula M, Tamir A et al. Gastric emptying time and gastric motility in patients with Parkinson’s disease. Mov Disord 2001; 16: 1041-1047
- 60 Natale G, Pasquali L, Ruggieri S et al. Parkinson’s disease and the gut: a well known clinical association in need of an effective cure and explanation. Neurogastroenterol Motil 2008; 20: 741-749
- 61 Unger MM, Hattemer K, Möller JC et al. Real-time visualization of altered gastric motility by magnetic resonance imaging in patients with Parkinson’s disease. Mov Disord 2010; 25: 623-628
- 62 Unger MM, Möller JC, Mankel K et al. Patients with idiopathic rapid-eye-movement sleep behavior disorder show normal gastric motility assessed by the 13C-octanoate breath test. Mov Disord 2011; 26: 2559-2563
- 63 La Rovere MT, Pinna GD, Hohnloser SH et al. Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials. Circulation 2001; 103: 2072-2077
- 64 Bennett DA, Beckett LA, Murray AM et al. Prevalence of parkinsonian signs and associated mortality in a community population of older people. N Engl J Med 1996; 334: 71-76
- 65 Marsh L, McDonald WM, Cummings J et al. Provisional diagnostic criteria for depression in Parkinson’s disease: report of an NINDS/NIMH Work Group. Mov Disord 2006; 21: 148-158
- 66 Leentjens AF, Van den Akker M, Metsemakers JF et al. Higher incidence of depression preceding the onset of Parkinson’s disease: a register study. Mov Disord 2003; 18: 414-418
- 67 Santamaría J, Tolosa E, Valles A. Parkinson’s disease with depression: a possible subgroup of idiopathic parkinsonism. Neurology 1986; 36: 1130-1133
- 68 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: 1641-1649
- 69 O’Sullivan SS, Williams DR, Gallagher DA et al. Nonmotor symptoms as presenting complaints in Parkinson’s disease: a clinicopathological study. Mov Disord 2008; 23: 101-106
- 70 Liepelt-Scarfone I, Behnke S, Godau J et al. Relation of risk factors and putative premotor markers for Parkinson’s disease. J Neural Transm 2011; 118: 579-585
- 71 Buter TC, van den Hout A, Matthews FE et al. Dementia and survival in Parkinson disease: a 12-year population study. Neurology 2008; 70: 1017-1022
- 72 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: 837-844
- 73 Aarsland D, Bronnick K, Williams-Gray C et al. Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology 2010; 75: 1062-1069
- 74 Litvan I, Aarsland D, Adler CH et al. MDS Task Force on mild cognitive impairment in Parkinson’s disease: critical review of PD-MCI. Mov Disord 2011; 26: 1814-1824
- 75 Emre M, Aarsland D, Brown R et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 2007; 22: 1689-1707
- 76 Williams-Gray CH, Evans JR, Goris A et al. The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain 2009; 132: 2958-2969
- 77 Aarsland D, Brønnick K, Larsen JP et al. Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study. Neurology 2009; 72: 1121-1126
- 78 Elgh E, Domellöf M, Linder J et al. Cognitive function in early Parkinson’s disease: a population-based study. Eur J Neurol 2009; 16: 1278-1284
- 79 Foltynie T, Brayne CE, Robbins TW et al. The cognitive ability of an incident cohort of Parkinson’s patients in the UK. The CamPaIGN study. Brain 2004; 127: 550-560
- 80 Rosenthal E, Brennan L, Xie S et al. Association between cognition and function in patients with Parkinson disease with and without dementia. Mov Disord 2010; 25: 1170-1176
- 81 Aarsland D, Perry R, Brown A et al. Neuropathology of dementia in Parkinson’s disease: a prospective, community-based study. Ann Neurol 2005; 58: 773-776
- 82 Compta Y, Parkkinen L, O’Sullivan SS et al. Lewy- and Alzheimer-type pathologies in Parkinson’s disease dementia: which is more important?. Brain 2011; 134: 1493-1505
- 83 Kotzbauer PT, Cairns NJ, Campbell MC et al. Pathologic accumulation of α-synuclein and Aβ in Parkinson disease patients with dementia. Arch Neurol 2012; 69: 1326-1331
- 84 Sabbagh MN, Adler CH, Lahti TJ et al. Parkinson disease with dementia: comparing patients with and without Alzheimer pathology. Alzheimer Dis Assoc Disord 2009; 23: 295-297
- 85 Setó-Salvia N, Clarimón J, Pagonabarraga J et al. Dementia risk in Parkinson disease: disentangling the role of MAPT haplotypes. Arch Neurol 2011; 68: 359-364
- 86 Wills J, Jones J, Haggerty T et al. Elevated tauopathy and alpha-synuclein pathology in postmortem Parkinson’s disease brains with and without dementia. Exp Neurol 2010; 225: 210-218
- 87 Goker-Alpan O, Stubblefield BK, Giasson BI et al. Glucocerebrosidase is present in α-synuclein inclusions in Lewy body disorders. Acta Neuropathol 2010; 120: 641-649
- 88 Nalls MA, Duran R, Lopez G et al. A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA Neurol 2013; 15: 1-9
- 89 Gomperts SN, Rentz DM, Moran E et al. Imaging amyloid deposition in Lewy body diseases. Neurology 2008; 71: 903-910
- 90 Tiraboschi P, Hansen LA, Alford M et al. Cholinergic dysfunction in diseases with Lewy bodies. Neurology 2000; 54: 407-411
- 91 Kotagal V, Albin RL, Müller ML et al. Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease. Ann Neurol 2012; 71: 560-568
- 92 Kehagia AA, Barker RA, Robbins TW. Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson’s disease. Lancet Neurol 2010; 9: 1200-1213
- 93 Molano J, Boeve B, Ferman T et al. Mild cognitive impairment associated with limbic and neocortical Lewy body disease: a clinicopathological study. Brain 2010; 133: 540-556
- 94 Schenck CH, Mahowald MW. REM sleep behavior disorder: clinical, developmental, and
neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep
2002; 25: 120-138
MissingFormLabel
- 95 Bjørnarå KA, Dietrichs E, Toft M. REM sleep behavior disorder in Parkinson’s disease – is there a gender difference?. Parkinsonism Relat Disord 2013; 19: 120-122
- 96 Ju YE, Larson-Prior L, Duntley S. Changing demographics in REM sleep behavior disorder: possible effect of autoimmunity and antidepressants. Sleep Med 2011; 12: 278-283
- 97 Aurora RN, Zak RS, Maganti RK et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med 2010; 6: 85-95
- 98 Gagnon JF, Postuma RB, Montplaisir J. Update on the pharmacology of REM sleep behavior disorder. Neurology 2006; 67: 742-747
- 99 Iranzo A, Molinuevo JL, Santamaría J et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol 2006; 5: 572-577
- 100 Postuma RB, Gagnon JF, Vendette M et al. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 2009; 72: 1296-1300
- 101 Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 1996; 46: 388-393
- 102 Iranzo A, Tolosa E, Gelpi E et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol 2013; 12: 443-453
- 103 Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older males initially diagnosed with idiopathic REM sleep behavior disorder (RBD): 16-year update on a previously reported series. Sleep Med 2013; 14: 744-748
- 104 Gagnon JF, Postuma RB, Mazza S et al. Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol 2006; 5: 424-432
- 105 Sixel-Döring F, Trautmann E, Mollenhauer B et al. Associated factors for REM sleep behavior disorder in Parkinson disease. Neurology 2011; 77: 1048-1054
- 106 American Academy of Sleep Medicine . The International Classification of Sleep Disorders: Diagnostic and Coding Manual (ICSD-2). 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005
- 107 Boeve BF, Molano JR, Ferman TJ et al. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behaviour disorder in an aging and dementia cohort. Sleep Med 2011; 12: 445-453
- 108 Li SX, Wing YK, Lam SP et al. Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK). Sleep Med 2010; 11: 43-48
- 109 Postuma RB, Arnulf I, Hogl B et al. A single-question screen for rapid eye movement sleep behaviour disorder: a multicenter validation study. Mov Disord 2012; 27: 913-916
- 110 Stiasny-Kolster K, Mayer G, Schäfer S et al. The REM sleep behavior disorder screening questionnaire – a new diagnostic instrument. Mov Disord 2007; 22: 2386-2393
- 111 Postuma RB, Gagnon JF, Rompré S et al. Severity of REM atonia loss in idiopathic REM sleep behavior disorder predicts Parkinson disease. Neurology 2010; 74: 239-244
- 112 Gagnon JF, Vendette M, Postuma RB et al. Mild cognitive impairment in rapid eye movement sleep behavior disorder and Parkinson’s disease. Ann Neurol 2009; 66: 39-47
- 113 Massicotte-Marquez J, Décary A, Gagnon JF et al. Executive dysfunction and memory impairment in idiopathic REM sleep behavior disorder. Neurology 2008; 70: 1250-1257
- 114 Postuma RB, Gagnon JF, Vendette M et al. Idiopathic REM sleep behavior disorder in the transition to degenerative disease. Mov Disord 2009; 24: 2225-2232
- 115 Postuma RB, Bertrand JA, Montplaisir J et al. Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson’s disease: a prospective study. Mov Disord 2012; 27: 720-726
- 116 Dang-Vu TT, Gagnon JF, Vendette M et al. Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder. Neurology 2012; 79: 2302-2306
- 117 Vendette M, Montplaisir J, Gosselin N et al. Brain perfusion anomalies in rapid eye movement sleep behaviour disorder with mild cognitive impairment. Mov Disord 2012; 27: 1255-1261
- 118 Boeve BF, Silber MH, Ferman TJ. REM sleep behavior disorder in Parkinson’s disease and dementia with Lewy bodies. J Geriatr Psychiatry Neurol 2004; 17: 146-157
- 119 Dugger BN, Boeve BF, Murray ME et al. Rapid eye movement sleep behavior disorder and subtypes in autopsy-confirmed dementia with Lewy bodies. Mov Disord 2012; 27: 72-78
- 120 Ferman TJ, Smith GE, Boeve BF et al. DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging. Neurology 2004; 62: 181-187
- 121 Ferman TJ, Boeve BF, Smith GE et al. Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology 2011; 77: 875-882
- 122 Boeve BF, Silber MH, Ferman TJ et al. Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med 2013; 14: 754-762
- 123 Iranzo A, Santamaría J, Rye DB et al. Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD. Neurology 2005; 65: 247-252
- 124 Plazzi G, Corsini R, Provini F et al. REM sleep behavior disorders in multiple system atrophy. Neurology 1997; 48: 1094-1097
- 125 Tachibana N, Kimura K, Kitajima K et al. REM sleep motor dysfunction in multiple system atrophy: with special emphasis on sleep talk as its early clinical manifestation. J Neurol Neurosurg Psychiatry 1997; 63: 678-681
- 126 Vetrugno R, Provini F, Cortelli P et al. Sleep disorders in multiple system atrophy: a correlative video-polysomnographic study. Sleep Med 2004; 5: 21-30
- 127 Postuma RB, Gagnon JF, Vendette M et al. Manifestations of Parkinson disease differ in association with REM sleep behavior disorder. Mov Disord 2008; 23: 1665-7162
- 128 Postuma RB, Gagnon JF, Vendette M et al. REM sleep behaviour disorder in Parkinson’s disease is associated with specific motor features. J Neurol Neurosurg Psychiatry 2008; 79: 1117-1121
- 129 Postuma RB, Gagnon JF, Vendette M et al. Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson’s disease. Brain 2009; 132: 3298-3307
- 130 Vendette M, Gagnon JF, Décary A et al. REM sleep behavior disorder predicts cognitive impairment in Parkinson disease without dementia. Neurology 2007; 69: 1843-1849
- 131 Jennum P, Mayer G, Ju YE et al. Morbidities in rapid eye movement sleep behavior disorders. Sleep Med 2013; 14: 782-787
- 132 Stockner H, Iranzo A, Seppi K et al. Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder. Mov Disord 2009; 24: 1906-1909
- 133 Unger MM, Möller JC, Stiasny-Kolster K et al. Assessment of idiopathic rapid-eye-movement sleep behaviour disorder by transcranial sonography, olfactory function test, and FP-CIT-SPECT. Mov Disord 2008; 23: 596-599
- 134 Miyamoto M, Miyamoto T, Iwanami M et al. Preclinical substantia nigra dysfunction in rapid eye movement sleep behaviour disorder. Sleep Med 2012; 13: 102-106
- 135 Berg D, Behnke S, Seppi K et al. Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson’s disease. Mov Disord 2013; 28: 216-219
- 136 Hanyu H, Inoue Y, Sakurai H et al. Voxel-based magnetic resonance imaging study of structural brain changes in patients with idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord 2012; 18: 136-139
- 137 Unger MM, Belke M, Menzler K et al. Diffusion tensor imaging in idiopathic REM sleep behavior disorder reveals microstructural changes in the brainstem, substantia nigra, olfactory region, and other brain regions. Sleep 2010; 33: 767-773
- 138 Scherfler C, Frauscher B, Schocke M et al. White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor imaging and voxel-based morphometry study. Ann Neurol 2011; 69: 400-407
- 139 Hanoglu L, Ozer F, Meral H et al. Brainstem 1H-MR spectroscopy in patients with Parkinson’s disease with REM sleep behavior disorder and IPD patients without dream enactment behavior. Clin Neurol Neurosurg 2006; 108: 129-134
- 140 Iranzo A, Santamaria J, Pujol J et al. Brainstem proton magnetic resonance spectroscopy in idopathic REM sleep behavior disorder. Sleep 2002; 25: 867-870
- 141 Miyamoto M, Miyamoto T, Kubo J et al. Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H-MRS). Psychiatry Clin Neurosci 2000; 54: 350-351
- 142 Boeve BF, Dickson DW, Olson EJ et al. Insights into REM sleep behavior disorder pathophysiology in brainstem-predominant Lewy body disease. Sleep Med 2007; 8: 44-60
- 143 Boeve BF, Silber MH, Saper CB et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 2007; 130: 2770-2788
- 144 Uchiyama M, Isse K, Tanaka K et al. Incidental Lewy body disease in a patient with REM sleep behaviour disorder. Neurology 1995; 45: 709-712
- 145 Iranzo A, Aparicio J. A lesson from anatomy: focal brain lesions causing REM sleep behavior disorder. Sleep Med 2009; 10: 9-12
- 146 Albin RL, Koeppe RA, Chervin RD et al. Decreased striatal dopaminergic innervation in REM sleep behavior disorder. Neurology 2000; 55: 1410-1412
- 147 Eisensehr I, Linke R, Noachtar S et al. Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson’s disease and controls. Brain 2000; 123: 1155-1160
- 148 Iranzo A, Lomeña F, Stockner H et al. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected]. Lancet Neurol 2010; 9: 1070-1077
- 149 Iranzo A, Valldeoriola F, Lomeña F et al. Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 2011; 10: 797-805
- 150 Miyamoto T, Orimo S, Miyamoto M et al. Follow-up PET studies in case of idiopathic REM sleep behavior disorder. Sleep Med 2010; 11: 100-101
- 151 Eisensehr I, Linke R, Tatsch K et al. Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep behavior disorder, Parkinson’s disease, and controls. Sleep 2003; 26: 507-512
- 152 Miyamoto T, Miyamoto M, Inoue Y et al. Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder. Neurology 2006; 67: 2236-2238
- 153 Miyamoto T, Miyamoto M, Suzuki K et al. 123I-MIBG cardiac scintigraphy provides clues to the underlying neurodegenerative disorder in idiopathic REM sleep behavior disorder. Sleep 2008; 31: 717-723
- 154 Djaldetti R, Baron J, Ziv I et al. Gastric emptying in Parkinson’s disease: patients with and without response fluctuations. Neurology 1996; 46: 1051-1054
- 155 Unger MM, Möller JC, Mankel K et al. Postprandial ghrelin response is reduced in patients with Parkinson’s disease and idiopathic REM sleep behavior disorder: a peripheral biomarker for early Parkinson’s disease?. J Neurol 2011; 258: 982-990
- 156 Unger MM, Ekman R, Björklund AK et al. Unimpaired postprandial pancreatic polypeptide secretion in Parkinson’s disease and REM sleep behavior disorder. Mov Disord 2013; 28: 529-533
- 157 Duran R, Barrero FJ, Morales B et al. Plasma alpha-synuclein in patients with Parkinson’s disease with and without treatment. Mov Disord 2010; 25: 489-493
- 158 Lee PH, Lee G, Park HJ et al. The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy. J Neural Trans 2006; 113: 1435-1439
- 159 Li QX, Mok SS, Laughton KM et al. Plasma alpha-synuclein is decreased in subjects with Parkinson’s disease. Exp Neurol 2007; 204: 583-588
- 160 Smith LM, Schiess MC, Coffey MP et al. α-Synuclein and anti-α-synuclein antibodies in Parkinson’s disease, atypical Parkinson syndromes, REM sleep behavior disorder, and healthy controls. PLoS One 2012; 7: e52285
- 161 Foulds PG, Mitchell JD, Parker A et al. Phosphorylated α-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson’s disease. FASEB J 2011; 25: 4127-4137
- 162 El-Agnaf OM, Salem SA, Paleologou KE et al. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J 2006; 20: 419-425
- 163 Lin X, Cook TJ, Zabetian CP et al. DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease. Sci Rep 2012; 2: 954
- 164 Chen-Plotkin AS, Hu WT, Siderowf A et al. Plasma epidermal growth factor levels predict cognitive decline in Parkinson disease. Ann Neurol 2011; 69: 655-663
- 165 Godau J, Herfurth M, Kattner B et al. Increased serum insulin-like growth factor 1 in early idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 2010; 81: 536-538
- 166 Shehadeh LA, Yu K, Wang L et al. SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson’s disease. PLoS One 2010; 5: e9104
- 167 Molochnikov L, Rabey JM, Dobronevsky E et al. A molecular signature in blood identifies early Parkinson’s disease. Mol Neurodegener 2012; 7: 26
- 168 Double KL, Rowe DB, Carew-Jones FM et al. Anti-melanin antibodies are increased in sera in Parkinson’s disease. Exp Neurol 2009; 217: 297-301
- 169 Besong-Agbo D, Wolf E, Jessen F et al. Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease. Neurology 2013; 80: 169-175
- 170 Papachroni KK, Ninkina N, Papapanagiotou A et al. Autoantibodies to alpha-synuclein in inherited Parkinson’s disease. J Neurochem 2007; 101: 749-756
- 171 Yanamandra K, Gruden MA, Casaite V et al. α-synuclein reactive antibodies as diagnostic biomarkers in blood sera of Parkinson’s disease patients. PLoS One 2011; 6: e18513
- 172 Han M, Nagele E, DeMarshall C et al. Diagnosis of Parkinson’s disease based on disease-specific autoantibody profiles in human sera. PLoS One 2012; 7: e32383
- 173 Ascherio A, LeWitt PA, Xu K et al. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol 2009; 66: 1460-1468
- 174 Schwarzschild MA, Schwid SR, Marek K et al. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch Neurol 2008; 65: 716-723
- 175 Mollenhauer B, Locascio JJ, Schulz-Schaeffer W et al. α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 2011; 10: 230-240
- 176 Zhang J, Mattison HA, Liu C et al. Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease. Acta Neuropathol 2013; [Epub ahead of print]
- 177 Borroni B, Malinverno M, Gardoni F et al. Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy. Neurology 2008; 71: 1796-1803
- 178 Holmberg B, Johnels B, Blennow K et al. Cerebrospinal fluid Abeta42 is reduced in multiple system atrophy but normal in Parkinson’s disease and progressive supranuclear palsy. Mov Disord 2003; 18: 186-190
- 179 Siderowf A, Xie SX, Hurtig H et al. CSF amyloid {beta} 1-42 predicts cognitive decline in Parkinson disease. Neurology 2010; 75: 1055-1061
- 180 Aerts MB, Esselink RA, Abdo WF et al. CSF α-synuclein does not differentiate between parkinsonian disorders. Neurobiol Aging 2012; 33: 430.e1-430.e3
- 181 Hong Z, Shi M, Chung KA et al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 2010; 133: 713-726
- 182 Kang J-H, Irwin DJ, Chen-Plotkin AS et al. Association of cerebrospinal fluid Abeta1-42, t-tau, p-tau181 and alpha-synuclein levels with clinical features of early drug naïve Parkinson’s disease patients. JAMA Neurol 2013; Aug 26. doi: 10.1001/jamaneurol.2013.3861
- 183 Mollenhauer B, Cullen V, Kahn I et al. Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol 2008; 213: 315-325
- 184 Mollenhauer B, El-Agnaf OM, Marcus K et al. Quantification of α-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. Biomark Med 2010; 4: 683-699
- 185 Tokuda T, Salem SA, Allsop D et al. Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s disease. Biochem Biophys Res Commun 2006; 349: 162-166
- 186 Tokuda T, Qureshi MM, Ardah MT et al. Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 2010; 75: 1766-1772
- 187 Jesse S, Lehnert S, Jahn O et al. Differential sialylation of serpin A1 in the early diagnosis of Parkinson’s disease dementia. PLoS One 2012; 7: e48783
- 188 Brettschneider J, Petzold A, Süssmuth SD et al. Neurofilament heavy-chain NfH(SMI35) in cerebrospinal fluid supports the differential diagnosis of Parkinsonian syndromes. Mov Disord 2006; 21: 2224-2227
- 189 Holmberg B, Rosengren L, Karlsson JE et al. Increased cerebrospinal fluid levels of neurofilament protein in progressive supranuclear palsy and multiple-system atrophy compared with Parkinson’s disease. Mov Disord 1998; 13: 70-77
- 190 Bolner A, Pilleri M, De Riva V et al. Plasma and urinary HPLC-ED determination of the ratio of 8-OHdG/2-dG in Parkinson’s disease. Clin Lab 2011; 57: 859-866
- 191 Hirayama M, Nakamura T, Watanabe H et al. Urinary 8-hydroxydeoxyguanosine correlate with hallucinations rather than motor symptoms in Parkinson’s disease. Parkinsonism Relat Disord 2011; 17: 46-49
- 192 Sato S, Mizuno Y, Hattori N. Urinary 8-hydroxydeoxyguanosine levels as a biomarker for progression of Parkinson disease. Neurology 2005; 64: 1081-1083
- 193 Connolly J, Siderowf A, Clark CM et al. F2 isoprostane levels in plasma and urine do not support increased lipid peroxidation in cognitively impaired Parkinson disease patients. Cogn Behav Neurol 2008; 21: 83-86
- 194 Lee CY, Seet RC, Huang SH et al. Different patterns of oxidized lipid products in plasma and urine of dengue fever, stroke, and Parkinson’s disease patients: cautions in the use of biomarkers of oxidative stress. Antioxid Redox Signal 2009; 11: 407-420
- 195 Devic I, Hwang H, Edgar JS et al. Salivary α-synuclein and DJ-1: potential biomarkers for Parkinson’s disease. Brain 2011; 134: e178
- 196 Beach TG, Adler CH, Dugger BN et al. Submandibular gland biopsy for the diagnosis of Parkinson disease. J Neuropathol Exp Neurol 2013; 72: 130-136
- 197 Cersósimo MG, Perandones C, Micheli FE et al. Alpha-synuclein immunoreactivity in minor salivarygland biopsies of Parkinson’s disease patients. Mov Disord 2011; 26: 188-190
- 198 Shannon KM, Keshavarzian A, Dodiya HB et al. Is alpha-synuclein in the colon a biomarker for premotor Parkinson’s disease? Evidence from 3 cases. Mov Disord 2012; 27: 716-719
- 199 Shannon KM, Keshavarzian A, Mutlu E et al. Alpha-synuclein in colonic submucosa in early untreated Parkinson’s disease. Mov Disord 2012; 27: 709-715
- 200 Witt M, Bormann K, Gudziol V et al. Biopsies of olfactory epithelium in patients with Parkinson’s disease. Mov Disord 2009; 24: 906-914
- 201 Parnetti L, Castrioto A, Chiasserini D et al. Cerebrospinal fluid biomarkers in Parkinson disease. Nat Rev Neurol 2013; 9: 131-140
- 202 Mollenhauer B, Trautmann E, Taylor P et al. Total CSF α-synuclein is lower in de novo Parkinson patients than in healthy subjects. Neurosci Lett 2013; 532: 44-48
- 203 Shi M, Furay AR, Sossi V et al. DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function. Neurobiol Aging 2012; 33: 836.e5-836.e7