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Molecular Imaging and the Neuropathologies of Parkinson’s Disease

  • Paul Cumming
  • Per Borghammer
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 11)

Abstract

The main motor symptoms of Parkinson’s disease (PD) are linked to degeneration of the nigrostriatal dopamine (DA) fibers, especially those innervating the putamen. This degeneration can be assessed in molecular imaging studies with presynaptic tracers such as [18F]-fluoro-L-DOPA (FDOPA) and ligands for DA transporter ligands. However, the pathologies of PD are by no means limited to nigrostriatal loss. Results of post mortem and molecular imaging studies reveal parallel degenerations of cortical noradrenaline (NA) and serotonin (5-HT) innervations, which may contribute to affective and cognitive changes of PD. Especially in advanced PD, cognitive impairment can come to resemble that seen in Alzheimer’s dementia, as can the degeneration of acetylcholine innervations arising in the basal forebrain. The density of striatal DA D2 receptors increases in early untreated PD, consistent with denervation upregulation, but there is an accelerated rate of DA receptor loss as the disease advances. Animal studies and post mortem investigations reveal changes in brain opioid peptide systems, but these are poorly documented in imaging studies of PD. Relatively minor changes in the binding sites for GABA are reported in cortex and striatum of PD patients. There remains some controversy about the expression of the 18 kDa translocator protein (TSPO) in activated microglia as an indicator of an active inflammatory component of neurodegeneration in PD. A wide variety of autonomic disturbances contribute to the clinical syndrome of PD; the degeneration of myocardial sympathetic innervation can be revealed in SPECT studies of PD patients with autonomic failure. Considerable emphasis has been placed on investigations of cerebral blood flow and energy metabolism in PD. Due to the high variance of these physiological estimates, researchers have often employed normalization procedures for the sensitive detection of perturbations in relatively small patient groups. However, a widely used normalization to the global mean must be used with caution, as it can result in spurious findings of relative hypermetabolic changes in subcortical structures. A meta-analysis of the quantitative studies to date shows that there is in fact widespread hypometabolism and cerebral blood flow in the cerebral cortex, especially in frontal cortex and parietal association areas. These changes can bias the use of global mean normalization, and probably represent the pathophysiological basis of the cognitive impairment of PD.

Keywords

Parkinson’s disease PET Dopamine Serotonin Noradrenaline Receptors TSPO Cerebral blood flow CMRglc SPECT 

References

  1. Aarsland D, Zaccai J, Brayne C (2005) A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord 20(10):1255–1263PubMedGoogle Scholar
  2. Antonini A, Leenders KL, Reist H, Thomann R, Beer HF, Locher J (1993) Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and 11C-raclopride. Arch Neurol 50(5):474–480PubMedGoogle Scholar
  3. Antonini A, Schwarz J, Oertel WH, Beer HF, Madeja UD, Leenders KL (1994) [11C]raclopride and positron emission tomography in previously untreated patients with Parkinson’s disease: influence of l-dopa and lisuride therapy on striatal dopamine D2-receptors. Neurology 44(7):1325–1329PubMedGoogle Scholar
  4. Antonini A, Schwarz J, Oertel WH, Pogarell O, Leenders KL (1997) Long-term changes of striatal dopamine D2 receptors in patients with Parkinson’s disease: a study with positron emission tomography and [11C]raclopride. Mov Disord 12(1):33–38PubMedGoogle Scholar
  5. Antonini A, Kazumata K, Feigin A, Mandel F, Dhawan V, Margouleff C, Eidelberg D (1998) Differential diagnosis of parkinsonism with [18F]fluorodeoxyglucose and PET. Mov Disord 13(2):268–274PubMedGoogle Scholar
  6. Araki I, Kitahara M, Oida T, Kuno S (2000) Voiding dysfunction and Parkinson’s disease: urodynamic abnormalities and urinary symptoms. J Urol 164(5):1640–1643PubMedGoogle Scholar
  7. Asanuma K, Tang C, Ma Y, Dhawan V, Mattis P, Edwards C, Kaplitt MG, Feigin A, Eidelberg D (2006) Network modulation in the treatment of Parkinson’s disease. Brain 129(Pt 10):2667–2678PubMedGoogle Scholar
  8. Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21(10):1133–1145PubMedGoogle Scholar
  9. Aubin N, Curet O, Deffois A, Carter C (1998) Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice. J Neurochem 71(4):1635–1642PubMedGoogle Scholar
  10. Bartels AL, Willemsen AT, Doorduin J, de Vries EF, Dierckx RA, Leenders KL (2010) [11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson’s disease? Parkinsonism Relat Disord 16(1):57–59PubMedGoogle Scholar
  11. Berding G, Odin P, Brooks DJ, Nikkhah G, Matthies C, Peschel T, Shing M, Kolbe H, van Den Hoff J, Fricke H, Dengler R, Samii M, Knapp WH (2001) Resting regional cerebral glucose metabolism in advanced Parkinson’s disease studied in the off and on conditions with [(18)F]FDG-PET. Mov Disord 16(6):1014–1022PubMedGoogle Scholar
  12. Berger B, Trottier S, Gaspar P, Verney C, Alvarez C (1986) Major dopamine innervation of the cortical motor areas in the cynomolgus monkey. A radioautographic study with comparative assessment of serotonergic afferents. Neurosci Lett 72(2):121–127PubMedGoogle Scholar
  13. Bergman H, Wichmann T, Karmon B, DeLong MR (1994) The primate subthalamic nucleus II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 72(2):507–520PubMedGoogle Scholar
  14. Bohnen NI, Minoshima S, Giordani B, Frey KA, Kuhl DE (1999) Motor correlates of occipital glucose hypometabolism in Parkinson’s disease without dementia. Neurology 52(3):541–546PubMedGoogle Scholar
  15. Boileau I, Warsh JJ, Guttman M, Saint-Cyr JA, McCluskey T, Rusjan P, Houle S, Wilson AA, Meyer JH, Kish SJ (2008) Elevated serotonin transporter binding in depressed patients with Parkinson’s disease: a preliminary PET study with [11C]DASB. Mov Disord 23(12):1776–1780PubMedGoogle Scholar
  16. Bokobza B, Ruberg M, Scatton B, Javoy-Agid F, Agid Y (1984) [3H]spiperone binding, dopamine and HVA concentrations in Parkinson’s disease and supranuclear palsy. Eur J Pharmacol 99(2–3):167–175PubMedGoogle Scholar
  17. Borghammer P, Jonsdottir KY, Cumming P, Ostergaard K, Vang K, Ashkanian M, Vafaee M, Iversen P, Gjedde A (2008) Normalization in PET group comparison studies—the importance of a valid reference region. Neuroimage 40(2):529–540PubMedGoogle Scholar
  18. Borghammer P, Aanerud J, Gjedde A (2009a) Data-driven intensity normalization of PET group comparison studies is superior to global mean normalization. Neuroimage 46(4):981–988Google Scholar
  19. Borghammer P, Cumming P, Aanerud J, Forster S, Gjedde A (2009b) Subcortical elevation of metabolism in Parkinson’s disease—a critical reappraisal in the context of global mean normalization. Neuroimage 47(4):1514–1521Google Scholar
  20. Borghammer P, Chakravarty M, Jonsdottir KY, Sato N, Matsuda H, Ito K, Arahata Y, Kato T, Gjedde A (2010) Cortical hypometabolism and hypoperfusion in Parkinson’s disease is extensive: probably even at early disease stages. Brain Struct Funct 214(4):303–317PubMedGoogle Scholar
  21. Borghammer P, Hansen SB, Eggers C, Chakravarty M, Vang K, Aanerud J, Hilker R, Heiss WD, Rodell A, Munk OL, Keator D, Gjedde A (2011a) Glucose metabolism in small subcortical structures in Parkinson’s disease. Acta Neurologica Scandinavica.  doi:10.1111/j.1600-0404.2011.01556.x.
  22. Borghammer P, Cumming P, Ostergaard K, Gjedde A, Rodell A, Bailey CJ, Vafaee MS (2011b) Cerebral oxygen metabolism in patients with early Parkinson’s disease. J Neurol Sci. [Epub ahead of print]Google Scholar
  23. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211PubMedGoogle Scholar
  24. Braskie MN, Wilcox CE, Landau SM, O’Neil JP, Baker SL, Madison CM, Kluth JT, Jagust WJ (2008) Relationship of striatal dopamine synthesis capacity to age and cognition. J Neurosci 28(52):14320–14328PubMedGoogle Scholar
  25. Bruck A, Aalto S, Nurmi E, Bergman J, Rinne JO (2005) Cortical 6-[18F]fluoro-L-dopa uptake and frontal cognitive functions in early Parkinson’s disease. Neurobiol Aging 26(6):891–898PubMedGoogle Scholar
  26. Bucerius J, Joe AY, Schmaljohann J, Gundisch D, Minnerop M, Biersack HJ, Wullner U, Reinhardt MJ (2006) Feasibility of 2-deoxy-2-[18F]fluoro-d-glucose- A85380-PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo. Clin Res Cardiol 95(2):105–109PubMedGoogle Scholar
  27. Burn DJ, Rinne JO, Quinn NP, Lees AJ, Marsden CD, Brooks DJ (1995) Striatal opioid receptor binding in Parkinson’s disease, striatonigral degeneration and Steele–Richardson–Olszewski syndrome, a [11C]diprenorphine PET study. Brain 118(Pt 4):951–958PubMedGoogle Scholar
  28. Campos-Sousa RN, Quagliato E, da Silva BB, de Carvalho RM Jr, Ribeiro SC, de Carvalho DF (2003) Urinary symptoms in Parkinson’s disease: prevalence and associated factors. Arq Neuropsiquiatr 61(2B):359–363Google Scholar
  29. Carlsson A, Falck B, Hillarp NA (1962) Cellular localization of brain monoamines. Acta Physiol Scand Suppl 56(196):1–28PubMedGoogle Scholar
  30. Cash R, Ruberg M, Raisman R, Agid Y (1984) Adrenergic receptors in Parkinson’s disease. Brain Res 322(2):269–275PubMedGoogle Scholar
  31. Cash R, Dennis T, L’Heureux R, Raisman R, Javoy-Agid F, Scatton B (1987) Parkinson’s disease and dementia: norepinephrine and dopamine in locus ceruleus. Neurology 37(1):42–46PubMedGoogle Scholar
  32. Chan-Palay V (1988) Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer’s and Parkinson’s disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J Comp Neurol 273(4):543–557PubMedGoogle Scholar
  33. Chan-Palay V, Asan E (1989) Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson’s disease with and without dementia and depression. J Comp Neurol 287(3):373–392PubMedGoogle Scholar
  34. Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A (2005) Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease. Ann Neurol 58(6):963–967PubMedGoogle Scholar
  35. Cheng AV, Ferrier IN, Morris CM, Jabeen S, Sahgal A, McKeith IG, Edwardson JA, Perry RH, Perry EK (1991) Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer’s and Parkinson’s diseases. J Neurol Sci 106(1):50–55PubMedGoogle Scholar
  36. Chinaglia G, Landwehrmeyer B, Probst A, Palacios JM (1993) Serotoninergic terminal transporters are differentially affected in Parkinson’s disease and progressive supranuclear palsy: an autoradiographic study with [3H]citalopram. Neuroscience 54(3):691–699PubMedGoogle Scholar
  37. Cicchetti F, Brownell AL, Williams K, Chen YI, Livni E, Isacson O (2002) Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 15(6):991–998PubMedGoogle Scholar
  38. Cools R, Gibbs SE, Miyakawa A, Jagust W, D’Esposito M (2008) Working memory capacity predicts dopamine synthesis capacity in the human striatum. J Neurosci 28(5):1208–1212PubMedGoogle Scholar
  39. Coyle JT, Price DL, DeLong MR (1983) Alzheimer’s disease: a disorder of cortical cholinergic innervation. Science 219(4589):1184–1190PubMedGoogle Scholar
  40. Cumming P, Von Krosigk M, Reiner PB, McGeer EG, Vincent SR (1986) Absence of adrenaline neurons in the guinea pig brain: a combined immunohistochemical and high-performance liquid chromatography study. Neurosci Lett 63(2):125–130PubMedGoogle Scholar
  41. Cumming P, Munk OL, Doudet D (2001) Loss of metabolites from monkey striatum during PET with FDOPA. Synapse 41(3):212–218PubMedGoogle Scholar
  42. Cumming P, Pedersen MD, Minuzzi L, Mezzomo K, Danielsen EH, Iversen P, Aagaard D, Keiding S, Munk OL, Finsen B (2006) Distribution of PK11195 binding sites in porcine brain studied by autoradiography in vitro and by positron emission tomography. Synapse 59(7):418–426PubMedGoogle Scholar
  43. Defebvre LJ, Leduc V, Duhamel A, Lecouffe P, Pasquier F, Lamy-Lhullier C, Steinling M, Destee A (1999) Technetium HMPAO SPECT study in dementia with Lewy bodies, Alzheimer’s disease and idiopathic Parkinson’s disease. J Nucl Med 40(6):956–962PubMedGoogle Scholar
  44. Deguchi K, Sasaki I, Tsukaguchi M, Kamoda M, Touge T, Takeuchi H, Kuriyama S (2002) Abnormalities of rate-corrected QT intervals in Parkinson’s disease-a comparison with multiple system atrophy and progressive supranuclear palsy. J Neurol Sci 199(1–2):31–37PubMedGoogle Scholar
  45. Ding YS, Singhal T, Planeta-Wilson B, Gallezot JD, Nabulsi N, Labaree D, Ropchan J, Henry S, Williams W, Carson RE, Neumeister A, Malison RT (2010) PET imaging of the effects of age and cocaine on the norepinephrine transporter in the human brain using (S, S)-[(11)C]O-methylreboxetine and HRRT. Synapse 64(1):30–38PubMedGoogle Scholar
  46. Doudet DJ, Rosa-Neto P, Munk OL, Ruth TJ, Jivan S, Cumming P (2006) Effect of age on markers for monoaminergic neurons of normal and MPTP-lesioned rhesus monkeys: a multi-tracer PET study. Neuroimage 30(1):26–35PubMedGoogle Scholar
  47. Dukart J, Mueller K, Horstmann A, Vogt B, Frisch S, Barthel H, Becker G, Moller HE, Villringer A, Sabri O, Schroeter ML (2010) Differential effects of global and cerebellar normalization on detection and differentiation of dementia in FDG-PET studies. Neuroimage 49(2):1490–1495PubMedGoogle Scholar
  48. Eberling JL, Richardson BC, Reed BR, Wolfe N, Jagust WJ (1994) Cortical glucose metabolism in Parkinson’s disease without dementia. Neurobiol Aging 15(3):329–335PubMedGoogle Scholar
  49. Eidelberg D, Moeller JR, Dhawan V, Spetsieris P, Takikawa S, Ishikawa T, Chaly T, Robeson W, Margouleff D, Przedborski S et al (1994) The metabolic topography of parkinsonism. J Cereb Blood Flow Metab 14(5):783–801PubMedGoogle Scholar
  50. Ellis JR, Nathan PJ, Villemagne VL, Mulligan RS, Saunder T, Young K, Smith CL, Welch J, Woodward M, Wesnes KA, Savage G, Rowe CC (2009) Galantamine-induced improvements in cognitive function are not related to alterations in alpha(4)beta (2) nicotinic receptors in early Alzheimer’s disease as measured in vivo by 2-[18F]fluoro-A-85380 PET. Psychopharmacology (Berl) 202(1–3):79–91Google Scholar
  51. Engber TM, Susel Z, Kuo S, Gerfen CR, Chase TN (1991) Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats. Brain Res 552(1):113–118PubMedGoogle Scholar
  52. Fernandez A, de Ceballos ML, Rose S, Jenner P, Marsden CD (1996) Alterations in peptide levels in Parkinson’s disease and incidental Lewy body disease. Brain 119(Pt 3):823–830PubMedGoogle Scholar
  53. Fornai F, di Poggio AB, Pellegrini A, Ruggieri S, Paparelli A (2007) Noradrenaline in Parkinson’s disease: from disease progression to current therapeutics. Curr Med Chem 14(22):2330–2334PubMedGoogle Scholar
  54. Fox PT, Mintun MA, Reiman EM, Raichle ME (1988) Enhanced detection of focal brain responses using intersubject averaging and change-distribution analysis of subtracted PET images. J Cereb Blood Flow Metab 8(5):642–653PubMedGoogle Scholar
  55. Frackowiak RS, Herold S, Petty RK, Morgan-Hughes JA (1988) The cerebral metabolism of glucose and oxygen measured with positron tomography in patients with mitochondrial diseases. Brain 111(Pt 5):1009–1024PubMedGoogle Scholar
  56. Frisina PG, Haroutunian V, Libow LS (2009) The neuropathological basis for depression in Parkinson’s disease. Parkinsonism Relat Disord 15(2):144–148PubMedGoogle Scholar
  57. Gai WP, Halliday GM, Blumbergs PC, Geffen LB, Blessing WW (1991) Substance P-containing neurons in the mesopontine tegmentum are severely affected in Parkinson’s disease. Brain 114(Pt 5):2253–2267PubMedGoogle Scholar
  58. Gai WP, Geffen LB, Denoroy L, Blessing WW (1993) Loss of C1 and C3 epinephrine-synthesizing neurons in the medulla oblongata in Parkinson’s disease. Ann Neurol 33(4):357–367PubMedGoogle Scholar
  59. Gaspar P, Duyckaerts C, Alvarez C, Javoy-Agid F, Berger B (1991) Alterations of dopaminergic and noradrenergic innervations in motor cortex in Parkinson’s disease. Ann Neurol 30(3):365–374PubMedGoogle Scholar
  60. Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, Eggert K, Oertel W, Banati RB, Brooks DJ (2006) In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis 21(2):404–412PubMedGoogle Scholar
  61. Ghaemi M, Raethjen J, Hilker R, Rudolf J, Sobesky J, Deuschl G, Heiss WD (2002) Monosymptomatic resting tremor and Parkinson’s disease: a multitracer positron emission tomographic study. Mov Disord 17(4):782–788PubMedGoogle Scholar
  62. Goldstein DS, Holmes CS, Dendi R, Bruce SR, Li ST (2002) Orthostatic hypotension from sympathetic denervation in Parkinson’s disease. Neurology 58(8):1247–1255PubMedGoogle Scholar
  63. Goto S, Hirano A (1991) Catecholaminergic neurons in the parabrachial nucleus of normal individuals and patients with idiopathic Parkinson’s disease. Ann Neurol 30(2):192–196PubMedGoogle Scholar
  64. Gulyas B, Brockschnieder D, Nag S, Pavlova E, Kasa P, Beliczai Z, Legradi A, Gulya K, Thiele A, Dyrks T, Halldin C (2010) The norepinephrine transporter (NET) radioligand (S, S)-[18F]FMeNER-D2 shows significant decreases in NET density in the human brain in Alzheimer’s disease: a post-mortem autoradiographic study. Neurochem Int 56(6–7):789–798PubMedGoogle Scholar
  65. Guttman M, Boileau I, Warsh J, Saint-Cyr JA, Ginovart N, McCluskey T, Houle S, Wilson A, Mundo E, Rusjan P, Meyer J, Kish SJ (2007) Brain serotonin transporter binding in non-depressed patients with Parkinson’s disease. Eur J Neurol 14(5):523–528PubMedGoogle Scholar
  66. Habeck CG (2010) Basics of multivariate analysis in neuroimaging data. J Vis Exp (41). pii. 1988.  doi:10.3791/1988
  67. Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4(11):600–609PubMedGoogle Scholar
  68. Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, Lehrke R, Koulousakis A, Herholz K, Sturm V, Heiss WD (2004) Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson's disease. J Cereb Blood Flow Metab 24(1):7--16Google Scholar
  69. Hosey LA, Thompson JL, Metman LV, van den Munckhof P, Braun AR (2005) Temporal dynamics of cortical and subcortical responses to apomorphine in Parkinson disease: an H2(15)O PET study. Clin Neuropharmacol 28(1):18–27PubMedGoogle Scholar
  70. Hu MT, Taylor-Robinson SD, Chaudhuri KR, Bell JD, Labbe C, Cunningham VJ, Koepp MJ, Hammers A, Morris RG, Turjanski N, Brooks DJ (2000) Cortical dysfunction in non-demented Parkinson’s disease patients: a combined (31)P-MRS and (18)FDG-PET study. Brain 123(Pt 2):340–352PubMedGoogle Scholar
  71. Huang C, Tang C, Feigin A, Lesser M, Ma Y, Pourfar M, Dhawan V, Eidelberg D (2007) Changes in network activity with the progression of Parkinson’s disease. Brain 130(Pt 7):1834–1846PubMedGoogle Scholar
  72. Imon Y, Matsuda H, Ogawa M, Kogure D, Sunohara N (1999) SPECT image analysis using statistical parametric mapping in patients with Parkinson’s disease. J Nucl Med 40(10):1583–1589PubMedGoogle Scholar
  73. Iwanaga K, Wakabayashi K, Yoshimoto M, Tomita I, Satoh H, Takashima H, Satoh A, Seto M, Tsujihata M, Takahashi H (1999) Lewy body-type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases. Neurology 52(6):1269–1271PubMedGoogle Scholar
  74. Jakobsen S, Pedersen K, Smith DF, Jensen SB, Munk OL, Cumming P (2006) Detection of alpha2-adrenergic receptors in brain of living pig with 11C-yohimbine. J Nucl Med 47(12):2008–2015PubMedGoogle Scholar
  75. Javoy-Agid F, Ploska A, Agid Y (1981) Microtopography of tyrosine hydroxylase, glutamic acid decarboxylase, and choline acetyltransferase in the substantia nigra and ventral tegmental area of control and Parkinsonian brains. J Neurochem 37(5):1218–1227PubMedGoogle Scholar
  76. Jenner P, Taquet H, Mauborgne A, Benoliel JT, Cesselin F, Rose S, Javoy-Agid F, Agid Y, Marsden CD (1986) Lack of change in basal ganglia neuropeptide content following subacute 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine treatment of the common marmoset. J Neurochem 47(5):1548–1551PubMedGoogle Scholar
  77. Jokinen P, Bruck A, Aalto S, Forsback S, Parkkola R, Rinne JO (2009) Impaired cognitive performance in Parkinson’s disease is related to caudate dopaminergic hypofunction and hippocampal atrophy. Parkinsonism Relat Disord 15(2):88–93PubMedGoogle Scholar
  78. Kadir A, Almkvist O, Wall A, Langstrom B, Nordberg A (2006) PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer’s disease. Psychopharmacology (Berl) 188(4):509–520Google Scholar
  79. Kallio M, Suominen K, Haapaniemi T, Sotaniemi K, Myllyla VV, Astafiev S, Tolonen U (2004) Nocturnal cardiac autonomic regulation in Parkinson’s disease. Clin Auton Res 14(2):119–124PubMedGoogle Scholar
  80. Kalpouzos G, Chetelat G, Baron JC, Landeau B, Mevel K, Godeau C, Barre L, Constans JM, Viader F, Eustache F, Desgranges B (2009) Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging. Neurobiol Aging 30(1):112–124PubMedGoogle Scholar
  81. Kas A, Bottlaender M, Gallezot JD, Vidailhet M, Villafane G, Gregoire MC, Coulon C, Valette H, Dolle F, Ribeiro MJ, Hantraye P, Remy P (2009) Decrease of nicotinic receptors in the nigrostriatal system in Parkinson’s disease. J Cereb Blood Flow Metab 29(9):1601–1608PubMedGoogle Scholar
  82. Kawabata K, Tachibana H (1997) Evaluation of benzodiazepine receptor in the cerebral cortex of Parkinson’s disease using 123I-iomazenil SPECT. Nippon Rinsho 55(1):244–248PubMedGoogle Scholar
  83. Keeney PM, Xie J, Capaldi RA, Bennett JP Jr (2006) Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci 26(19):5256–5264PubMedGoogle Scholar
  84. Kitamura S, Ujike T, Kuroki S, Sakamoto S, Soeda T, Iio M, Terashi A (1988) Cerebral blood flow and oxygen metabolism in patients with Parkinson’s disease. No To Shinkei 40(10):979–985PubMedGoogle Scholar
  85. Koenigs M, Barbey AK, Postle BR, Grafman J (2009) Superior parietal cortex is critical for the manipulation of information in working memory. J Neurosci 29(47):14980–14986PubMedGoogle Scholar
  86. Koerts J, Leenders KL, Koning M, Portman AT, van Beilen M (2007) Striatal dopaminergic activity (FDOPA-PET) associated with cognitive items of a depression scale (MADRS) in Parkinson’s disease. Eur J Neurosci 25(10):3132–3136PubMedGoogle Scholar
  87. Koerts J, Leenders KL, Brouwer WH (2009) Cognitive dysfunction in non-demented Parkinson’s disease patients: controlled and automatic behavior. Cortex 45(8):922–929PubMedGoogle Scholar
  88. Koike Y, Takahashi A (1997) Autonomic dysfunction in Parkinson’s disease. Eur Neurol 38(2):8–12Google Scholar
  89. Kostic VS, Lecic D, Doder M, Marinkovic J, Filipovic S (1996) Prolactin and cortisol responses to fenfluramine in Parkinson’s disease. Biol Psychiatry 40(8):769–775PubMedGoogle Scholar
  90. Kumakura Y, Cumming P (2009) PET studies of cerebral levodopa metabolism: a review of clinical findings and modeling approaches. Neuroscientist 15(6):635–650PubMedGoogle Scholar
  91. Kumakura Y, Gjedde A, Danielsen EH, Christensen S, Cumming P (2006) Dopamine storage capacity in caudate and putamen of patients with early Parkinson’s disease: correlation with asymmetry of motor symptoms. J Cereb Blood Flow Metab 26(3):358–370PubMedGoogle Scholar
  92. Kumakura Y, Danielsen EH, Gjedde A, Vernaleken I, Buchholz HG, Heinz A, Grunder G, Bartenstein P, Cumming P (2010a) Elevated [(18)F]FDOPA utilization in the periaqueductal gray and medial nucleus accumbens of patients with early Parkinson’s disease. Neuroimage 49(4):2933–2939Google Scholar
  93. Kumakura Y, Vernaleken I, Buchholz HG, Borghammer P, Danielsen E, Grunder G, Heinz A, Bartenstein P, Cumming P (2010b) Age-dependent decline of steady state dopamine storage capacity of human brain: an FDOPA PET study. Neurobiol Aging 31(3):447–463Google Scholar
  94. la Fougere C, Grant S, Kostikov A, Schirrmacher R, Gravel P, Schipper H, Reader AEvans A, Thiel A (2010a) Where in vivo imaging meets cytoarchitectonics: the relationship between cortical thickness and neuronal density measured with high-resolution [(18)F]flumazenil-PET. Neuroimage 56(3):951–960Google Scholar
  95. la Fougere C, Popperl G, Levin J, Wangler B, Boning G, Uebleis C, Cumming P, Bartenstein P, Botzel K, Tatsch K (2010b) The value of the dopamine D2/3 receptor ligand 18F-desmethoxyfallypride for the differentiation of idiopathic and nonidiopathic parkinsonian syndromes. J Nucl Med 51(4):581–587Google Scholar
  96. Le Jeune F, Péron J, Grandjean D, Drapier S, Haegelen C, Garin E, Millet B, Vérin M (2010) Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study. Eur J Nucl Med Mol Imag 37(8):1512--1520Google Scholar
  97. Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, Wudel J, Pal PK, de la Fuente-Fernandez R, Calne DB, Stoessl AJ (2000) In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease. Ann Neurol 47(4):493–503PubMedGoogle Scholar
  98. Leenders KL, Wolfson L, Gibbs JM, Wise RJ, Causon R, Jones T, Legg NJ (1985) The effects of L-DOPA on regional cerebral blood flow and oxygen metabolism in patients with Parkinson’s disease. Brain 108(Pt 1):171–191PubMedGoogle Scholar
  99. Leenders KL, Perani D, Lammertsma AA, Heather JD, Buckingham P, Healy MJ, Gibbs JM, Wise RJ, Hatazawa J, Herold S et al (1990) Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. Brain 113(Pt 1):27–47PubMedGoogle Scholar
  100. Levin BE, Llabre MM, Reisman S, Weiner WJ, Sanchez-Ramos J, Singer C, Brown MC (1991) Visuospatial impairment in Parkinson’s disease. Neurology 41(3):365–369PubMedGoogle Scholar
  101. Lloyd K, Hornykiewicz O (1970) Parkinson’s disease: activity of L-dopa decarboxylase in discrete brain regions. Science 170(963):1212–1213PubMedGoogle Scholar
  102. Lotze M, Reimold M, Heymans U, Laihinen A, Patt M, Halsband U (2009) Reduced ventrolateral fMRI response during observation of emotional gestures related to the degree of dopaminergic impairment in Parkinson disease. J Cogn Neurosci 21(7):1321–1331PubMedGoogle Scholar
  103. Loughlin SE, Foote SL, Fallon JH (1982) Locus coeruleus projections to cortex: topography, morphology and collateralization. Brain Res Bull 9(1–6):287–294PubMedGoogle Scholar
  104. Ma Y, Tang C, Spetsieris PG, Dhawan V, Eidelberg D (2007) Abnormal metabolic network activity in Parkinson’s disease: test–retest reproducibility. J Cereb Blood Flow Metab 27(3):597–605PubMedGoogle Scholar
  105. Makuuchi M, Kaminaga T, Sugishita M (2003) Both parietal lobes are involved in drawing: a functional MRI study and implications for constructional apraxia. Brain Res Cogn Brain Res 16(3):338–347PubMedGoogle Scholar
  106. Malessa S, Hirsch EC, Cervera P, Duyckaerts C, Agid Y (1990) Catecholaminergic systems in the medulla oblongata in parkinsonian syndromes: a quantitative immunohistochemical study in Parkinson’s disease, progressive supranuclear palsy, and striatonigral degeneration. Neurology 40(11):1739–1743PubMedGoogle Scholar
  107. Maloteaux JM, Laterre EC, Laduron PM, Javoy-Agid F, Agid Y (1988a) Decrease of serotonin-S2 receptors in temporal cortex of patients with Parkinson’s disease and progressive supranuclear palsy. Mov Disord 3(3):255–262Google Scholar
  108. Maloteaux JM, Luabeya MA, Vanisberg MA, Laterre EC, Laduron PM, Javoy-Agid F, Agid Y (1988b) Benzodiazepine receptors in normal human brain, in Parkinson’s disease and in progressive supranuclear palsy. Brain Res 446(2):321–332Google Scholar
  109. Marie RM, Barre L, Rioux P, Allain P, Lechevalier B, Baron JC (1995) PET imaging of neocortical monoaminergic terminals in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 9(1):55–71PubMedGoogle Scholar
  110. Marie RM, Barre L, Dupuy B, Viader F, Defer G, Baron JC (1999) Relationships between striatal dopamine denervation and frontal executive tests in Parkinson’s disease. Neurosci Lett 260(2):77–80PubMedGoogle Scholar
  111. Mattila PM, Roytta M, Lonnberg P, Marjamaki P, Helenius H, Rinne JO (2001) Choline acetytransferase activity and striatal dopamine receptors in Parkinson’s disease in relation to cognitive impairment. Acta Neuropathol 102(2):160–166PubMedGoogle Scholar
  112. Mavridis M, Degryse AD, Lategan AJ, Marien MR, Colpaert FC (1991) Effects of locus coeruleus lesions on parkinsonian signs, striatal dopamine and substantia nigra cell loss after 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine in monkeys: a possible role for the locus coeruleus in the progression of Parkinson’s disease. Neuroscience 41(2–3):507–523PubMedGoogle Scholar
  113. McGeer PL, Schwab C, Parent A, Doudet D (2003) Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine administration. Ann Neurol 54(5):599–604PubMedGoogle Scholar
  114. Mehta MA, Sahakian BJ, McKenna PJ, Robbins TW (1999) Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in Parkinson’s disease. Psychopharmacology (Berl) 146(2):162–174Google Scholar
  115. Mehta MA, Montgomery AJ, Kitamura Y, Grasby PM (2008) Dopamine D2 receptor occupancy levels of acute sulpiride challenges that produce working memory and learning impairments in healthy volunteers. Psychopharmacology (Berl) 196(1):157–165Google Scholar
  116. Melzer TR, Watts R, Macaskill MR, Pearson JF, Rueger S, Pitcher TL, Livingston L, Graham C, Keenan R, Shankaranarayanan A, Alsop DC, Dalrymple-Alford JC, Anderson TJ (2011) Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson’s disease. Brain 134(Pt 3):845–855Google Scholar
  117. Minoshima S, Frey KA, Foster NL, Kuhl DE (1995) Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr 19(4):541–547PubMedGoogle Scholar
  118. Moeller JR, Ishikawa T, Dhawan V, Spetsieris P, Mandel F, Alexander GE, Grady C, Pietrini P, Eidelberg D (1996) The metabolic topography of normal aging. J Cereb Blood Flow Metab 16(3):385–398PubMedGoogle Scholar
  119. Mohanakumar KP, Muralikrishnan D, Thomas B (2000) Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced neurotoxicity. Brain Res 864(2):281–290PubMedGoogle Scholar
  120. Moore RY, Whone AL, Brooks DJ (2008) Extrastriatal monoamine neuron function in Parkinson’s disease: an 18F-dopa PET study. Neurobiol Dis 29(3):381–390PubMedGoogle Scholar
  121. Muslimovic D, Post B, Speelman JD, Schmand B (2005) Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 65(8):1239–1245PubMedGoogle Scholar
  122. Nagano-Saito A, Kato T, Arahata Y, Washimi Y, Nakamura A, Abe Y, Yamada T, Iwai K, Hatano K, Kawasumi Y, Kachi T, Dagher A, Ito K (2004) Cognitive- and motor-related regions in Parkinson’s disease: FDOPA and FDG PET studies. Neuroimage 22(2):553–561PubMedGoogle Scholar
  123. Nagatsu T, Kato T, Numata Y, Ikuta K, Sano M (1977) Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain. Clin Chim Acta 75(2):221–232PubMedGoogle Scholar
  124. Nahmias C, Garnett ES, Firnau G, Lang A (1985) Striatal dopamine distribution in parkinsonian patients during life. J Neurol Sci 69(3):223–230PubMedGoogle Scholar
  125. Obeso JA, Marin C, Rodriguez-Oroz C, Blesa J, Benitez-Temino B, Mena-Segovia J, Rodriguez M, Olanow CW (2008) The basal ganglia in Parkinson’s disease: current concepts and unexplained observations. Ann Neurol 64(2):S30–S46Google Scholar
  126. Ohama E, Ikuta F (1976) Parkinson’s disease: distribution of Lewy bodies and monoamine neuron system. Acta Neuropathol 34(4):311–319PubMedGoogle Scholar
  127. Ohm TG, Busch C, Bohl J (1997) Unbiased estimation of neuronal numbers in the human nucleus coeruleus during aging. Neurobiol Aging 18(4):393–399PubMedGoogle Scholar
  128. Ohyama M, Senda M, Ishiwata K, Kitamura S, Mishina M, Ishii K, Toyama H, Oda K, Katayama Y (1999) Preserved benzodiazepine receptors in Alzheimer’s disease measured with C-11 flumazenil PET and I-123 iomazenil SPECT in comparison with CBF. Ann Nucl Med 13(5):309–315PubMedGoogle Scholar
  129. Orskov L, Jakobsen J, Dupont E, de Fine Olivarius B, Christensen NJ (1987) Autonomic function in parkinsonian patients relates to duration of disease. Neurology 37(7):1173–1178PubMedGoogle Scholar
  130. Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T (2005) Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol 57(2):168–175PubMedGoogle Scholar
  131. Palner M, Kjaerby C, Knudsen GM, Cumming P (2010) Effects of unilateral 6-OHDA lesions on [(3)H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat. Neurochem Int 58(3):243–247Google Scholar
  132. Paulus W, Jellinger K (1991) The neuropathologic basis of different clinical subgroups of Parkinson’s disease. J Neuropathol Exp Neurol 50(6):743–755PubMedGoogle Scholar
  133. Pavese N, Metta V, Bose SK, Chaudhuri KR, Brooks DJ (2010) Fatigue in Parkinson’s disease is linked to striatal and limbic serotonergic dysfunction. Brain 133(11):3434–3443PubMedGoogle Scholar
  134. Perez-Otano I, Luquin MR, Oset C, Herrero MT, Kupsch A, Oertel W, Obeso JA, Del Rio J (1995) Neurotoxicity induced by prenatal exposure to MPTP on the monoaminergic and peptidergic systems of the marmoset brain. Exp Neurol 131(1):108–113PubMedGoogle Scholar
  135. Perry EK, Perry RH, Candy JM, Fairbairn AF, Blessed G, Dick DJ, Tomlinson BE (1984) Cortical serotonin-S2 receptor binding abnormalities in patients with Alzheimer’s disease: comparisons with Parkinson’s disease. Neurosci Lett 51(3):353–357PubMedGoogle Scholar
  136. Perry EK, McKeith I, Thompson P, Marshall E, Kerwin J, Jabeen S, Edwardson JA, Ince P, Blessed G, Irving D et al (1991) Topography, extent, and clinical relevance of neurochemical deficits in dementia of Lewy body type, Parkinson’s disease, and Alzheimer’s disease. Ann N Y Acad Sci 640:197–202PubMedGoogle Scholar
  137. Piccini P, Weeks RA, Brooks DJ (1997) Alterations in opioid receptor binding in Parkinson’s disease patients with levodopa-induced dyskinesias. Ann Neurol 42(5):720–726PubMedGoogle Scholar
  138. Pifl C, Hornykiewicz O (2006) Dopamine turnover is upregulated in the caudate/putamen of asymptomatic MPTP-treated rhesus monkeys. Neurochem Int 49(5):519–524PubMedGoogle Scholar
  139. Politis M, Wu K, Loane C, Turkheimer FE, Molloy S, Brooks DJ, Piccini P (2010) Depressive symptoms in PD correlate with higher 5-HTT binding in raphe and limbic structures. Neurology 75(21):1920–1927PubMedGoogle Scholar
  140. Powers WJ, Videen TO, Markham J, Black KJ, Golchin N, Perlmutter JS (2008) Cerebral mitochondrial metabolism in early Parkinson’s disease. J Cereb Blood Flow Metab 28(10):1754–1760PubMedGoogle Scholar
  141. Purba JS, Hofman MA, Swaab DF (1994) Decreased number of oxytocin-immunoreactive neurons in the paraventricular nucleus of the hypothalamus in Parkinson’s disease. Neurology 44(1):84–89PubMedGoogle Scholar
  142. Raffel DM, Koeppe RA, Little R, Wang CN, Liu S, Junck L, Heumann M, Gilman S (2006) PET measurement of cardiac and nigrostriatal denervation in Parkinsonian syndromes. J Nucl Med 47(11):1769–1777PubMedGoogle Scholar
  143. Rektorova I, Srovnalova H, Kubikova R, Prasek J (2008) Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson’s disease. Mov Disord 23(11):1580–1587PubMedGoogle Scholar
  144. Remy P, Doder M, Lees A, Turjanski N, Brooks D (2005) Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128(Pt 6):1314–1322PubMedGoogle Scholar
  145. Rodriguez-Ferreiro J, Cuetos F, Herrera E, Menendez M, Ribacoba R (2010) Cognitive impairment in Parkinson’s disease without dementia. Mov Disord 25(13):2136–2141PubMedGoogle Scholar
  146. Rommelfanger KS, Weinshenker D (2007) Norepinephrine: the redheaded stepchild of Parkinson’s disease. Biochem Pharmacol 74(2):177–190PubMedGoogle Scholar
  147. Sakakibara R, Shinotoh H, Uchiyama T, Yoshiyama M, Hattori T, Yamanishi T (2001) SPECT imaging of the dopamine transporter with [(123)I]-beta-CIT reveals marked decline of nigrostriatal dopaminergic function in Parkinson’s disease with urinary dysfunction. J Neurol Sci 187(1–2):55–59PubMedGoogle Scholar
  148. Sakakibara R, Odaka T, Uchiyama T, Asahina M, Yamaguchi K, Yamaguchi T, Yamanishi T, Hattori T (2003) Colonic transit time and rectoanal videomanometry in Parkinson’s disease. J Neurol Neurosurg Psychiatry 74(2):268–272PubMedGoogle Scholar
  149. Saper CB, Sorrentino DM, German DC, de Lacalle S (1991) Medullary catecholaminergic neurons in the normal human brain and in Parkinson’s disease. Ann Neurol 29(6):577–584PubMedGoogle Scholar
  150. Scatton B, Javoy-Agid F, Rouquier L, Dubois B, Agid Y (1983) Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease. Brain Res 275(2):321–328PubMedGoogle Scholar
  151. Scatton B, Dennis T, L’Heureux R, Monfort JC, Duyckaerts C, Javoy-Agid F (1986) Degeneration of noradrenergic and serotonergic but not dopaminergic neurones in the lumbar spinal cord of parkinsonian patients. Brain Res 380(1):181–185PubMedGoogle Scholar
  152. Schenck CH, Bundlie SR, Mahowald MW (1996) Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 46(2):388–393PubMedGoogle Scholar
  153. Schneider JS (1990) Chronic exposure to low doses of MPTP II. Neurochemical and pathological consequences in cognitively-impaired, motor asymptomatic monkeys. Brain Res 534(1–2):25–36PubMedGoogle Scholar
  154. Selby G (1968) Stereotactic surgery for the relief of Parkinson's disease. 2. An analysis of the results in a series of 303 patients (413 operations). J Neurol Sci 5(2):343--375Google Scholar
  155. Shannak K, Rajput A, Rozdilsky B, Kish S, Gilbert J, Hornykiewicz O (1994) Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson’s disease and normal subjects. Brain Res 639(1):33–41PubMedGoogle Scholar
  156. Siessmeier T, Kienast T, Wrase J, Larsen JL, Braus DF, Smolka MN, Buchholz HG, Schreckenberger M, Rosch F, Cumming P, Mann K, Bartenstein P, Heinz A (2006) Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum correlates with prefrontal processing of affective stimuli. Eur J Neurosci 24(1):305–313PubMedGoogle Scholar
  157. Singaram C, Ashraf W, Gaumnitz EA, Torbey C, Sengupta A, Pfeiffer R, Quigley EM (1995) Dopaminergic defect of enteric nervous system in Parkinson’s disease patients with chronic constipation. Lancet 346(8979):861–864PubMedGoogle Scholar
  158. Singer C, Weiner WJ, Sanchez-Ramos JR (1992) Autonomic dysfunction in men with Parkinson’s disease. Eur Neurol 32(3):134–140PubMedGoogle Scholar
  159. Smith DF, Dyve S, Minuzzi L, Jakobsen S, Munk OL, Marthi K, Cumming P (2006) Inhibition of [11C]mirtazapine binding by alpha2-adrenoceptor antagonists studied by positron emission tomography in living porcine brain. Synapse 59(8):463–471PubMedGoogle Scholar
  160. Smith DF, Stork BS, Wegener G, Ashkanian M, Jakobsen S, Bender D, Audrain H, Vase KH, Hansen SB, Videbech P, Rosenberg R (2009) [11C]Mirtazapine binding in depressed antidepressant nonresponders studied by PET neuroimaging. Psychopharmacology (Berl) 206(1):133–140Google Scholar
  161. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28(5):897–916PubMedGoogle Scholar
  162. Stella F, Gobbi LT, Gobbi S, Oliani MM, Tanaka K, Pieruccini-Faria F (2007) Early impairment of cognitive functions in Parkinson’s disease. Arq Neuropsiquiatr 65(2B):406–410Google Scholar
  163. Stiasny-Kolster K, Doerr Y, Moller JC, Hoffken H, Behr TM, Oertel WH, Mayer G (2005) Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 128(Pt 1):126–137PubMedGoogle Scholar
  164. Suzuki M, Kurita A, Hashimoto M, Fukumitsu N, Abo M, Ito Y, Urashima M, Inoue K (2006) Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson’s disease. J Neurol Sci 240(1–2):15–19PubMedGoogle Scholar
  165. Swinn L, Schrag A, Viswanathan R, Bloem BR, Lees A, Quinn N (2003) Sweating dysfunction in Parkinson’s disease. Mov Disord 18(12):1459–1463PubMedGoogle Scholar
  166. Takahashi H, Kato M, Takano H, Arakawa R, Okumura M, Otsuka T, Kodaka F, Hayashi M, Okubo Y, Ito H, Suhara T (2008) Differential contributions of prefrontal and hippocampal dopamine D(1) and D(2) receptors in human cognitive functions. J Neurosci 28(46):12032--12038Google Scholar
  167. Takahashi S, Tohgi H, Yonezawa H, Obara S, Yamazaki E (1999) The effect of trihexyphenidyl, an anticholinergic agent, on regional cerebral blood flow and oxygen metabolism in patients with Parkinson’s disease. J Neurol Sci 167(1):56–61PubMedGoogle Scholar
  168. Tang CC, Poston KL, Eckert T, Feigin A, Frucht S, Gudesblatt M, Dhawan V, Lesser M, Vonsattel JP, Fahn S, Eidelberg D (2010) Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet Neurol 9(2):149–158PubMedGoogle Scholar
  169. Thal LJ, Sharpless NS, Hirschhorn ID, Horowitz SG, Makman MH (1983) Striatal met-enkephalin concentration increases following nigrostriatal denervation. Biochem Pharmacol 32(22):3297–3301PubMedGoogle Scholar
  170. Tohgi H, Abe T, Takahashi S, Takahashi J, Hamato H (1993) Concentrations of serotonin and its related substances in the cerebrospinal fluid of parkinsonian patients and their relations to the severity of symptoms. Neurosci Lett 150(1):71–74PubMedGoogle Scholar
  171. Vafaee MS, Østergaard K, Sunde N, Gjedde A, Dupont E, Cumming P (2004) Focal changes of oxygen consumption in cerebral cortex of patients with Parkinson's disease during subthalamic stimulation. Neuroimage 22(2):966--974Google Scholar
  172. van Beilen M, Portman AT, Kiers HA, Maguire RP, Kaasinen V, Koning M, Pruim J, Leenders KL (2008) Striatal FDOPA uptake and cognition in advanced non-demented Parkinson’s disease: a clinical and FDOPA-PET study. Parkinsonism Relat Disord 14(3):224–228PubMedGoogle Scholar
  173. Van Camp N, Boisgard R, Kuhnast B, Theze B, Viel T, Gregoire MC, Chauveau F, Boutin H, Katsifis A, Dolle F, Tavitian B (2010) In vivo imaging of neuroinflammation: a comparative study between [(18)F]PBR111, [(11)C]CLINME and [(11)C]PK11195 in an acute rodent model. Eur J Nucl Med Mol Imaging 37(5):962–972PubMedGoogle Scholar
  174. Vernaleken I, Buchholz HG, Kumakura Y, Siessmeier T, Stoeter P, Bartenstein P, Cumming P, Grunder G (2007) ‘Prefrontal’ cognitive performance of healthy subjects positively correlates with cerebral FDOPA influx: an exploratory [18F]-fluoro-L-DOPA-PET investigation. Hum Brain Mapp 28(10):931–939PubMedGoogle Scholar
  175. Volpi R, Caffarra P, Scaglioni A, Maestri D, Chiodera P, Coiro V (1994) Restoration of ACTH/cortisol and LH responses to naloxone by chronic dopaminergic treatment in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 7(1):1–11PubMedGoogle Scholar
  176. Volpi R, Caffarra P, Boni S, Scaglioni A, Malvezzi L, Saginario A, Chiodera P, Coiro V (1997a) ACTH/cortisol involvement in the serotonergic disorder affecting the parkinsonian brain. Neuropsychobiology 35(2):73–78Google Scholar
  177. Volpi R, Caffarra P, Scaglioni A, Boni S, Saginario A, Chiodera P, Coiro V (1997b) Defective 5-HT 1-receptor-mediated neurotransmission in the control of growth hormone secretion in Parkinson’s disease. Neuropsychobiology 35(2):79–83Google Scholar
  178. von Economo C (1931) Encephalitis lethargica. Its sequelae and treatment. (trans: Newman KO). Oxford University Press, LondonGoogle Scholar
  179. Wakabayashi K, Takahashi H (1997) The intermediolateral nucleus and Clarke’s column in Parkinson’s disease. Acta Neuropathol 94(3):287–289PubMedGoogle Scholar
  180. Weder B, Azari NP, Knorr U, Seitz RJ, Keel A, Nienhusmeier M, Maguire RP, Leenders KL, Ludin HP (2000) Disturbed functional brain interactions underlying deficient tactile object discrimination in Parkinson’s disease. Hum Brain Mapp 11(3):131–145PubMedGoogle Scholar
  181. Weihe E, Schutz B, Hartschuh W, Anlauf M, Schafer MK, Eiden LE (2005) Coexpression of cholinergic and noradrenergic phenotypes in human and nonhuman autonomic nervous system. J Comp Neurol 492(3):370–379PubMedGoogle Scholar
  182. Weintraub D, Newberg AB, Cary MS, Siderowf AD, Moberg PJ, Kleiner-Fisman G, Duda JE, Stern MB, Mozley D, Katz IR (2005) Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson’s disease. J Nucl Med 46(2):227–232PubMedGoogle Scholar
  183. Whittington CJ, Podd J, Stewart-Williams S (2006) Memory deficits in Parkinson’s disease. J Clin Exp Neuropsychol 28(5):738–754PubMedGoogle Scholar
  184. Williams-Gray CH, Foltynie T, Brayne CE, Robbins TW, Barker RA (2007) Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain 130(Pt 7):1787–1798PubMedGoogle Scholar
  185. Winge K, Werdelin LM, Nielsen KK, Stimpel H (2004) Effects of dopaminergic treatment on bladder function in Parkinson’s disease. Neurourol Urodyn 23(7):689–696PubMedGoogle Scholar
  186. Winge K, Friberg L, Werdelin L, Nielsen KK, Stimpel H (2005) Relationship between nigrostriatal dopaminergic degeneration, urinary symptoms, and bladder control in Parkinson’s disease. Eur J Neurol 12(11):842–850PubMedGoogle Scholar
  187. Wong KK, Muller ML, Kuwabara H, Studenski SA, Bohnen NI (2010) Olfactory loss and nigrostriatal dopaminergic denervation in the elderly. Neurosci Lett 484(3):163–167PubMedGoogle Scholar
  188. Yakushev I, Hammers A, Fellgiebel A, Schmidtmann I, Scheurich A, Buchholz HG, Peters J, Bartenstein P, Lieb K, Schreckenberger M (2009) SPM-based count normalization provides excellent discrimination of mild Alzheimer’s disease and amnestic mild cognitive impairment from healthy aging. Neuroimage 44(1):43–50PubMedGoogle Scholar
  189. Yoshita M (1998) Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 155(1):60–67PubMedGoogle Scholar
  190. Zarow C, Lyness SA, Mortimer JA, Chui HC (2003) Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 60(3):337–341PubMedGoogle Scholar
  191. Zweig RM, Cardillo JE, Cohen M, Giere S, Hedreen JC (1993) The locus ceruleus and dementia in Parkinson’s disease. Neurology 43(5):986–991PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Nuclear MedicineLudwig-Maximilian’s University of MunichMunichGermany
  2. 2.Department of Nuclear Medicine and PET CenterAarhus University HospitalAarhusDenmark
  3. 3.Department of Nuclear MedicineKlinikum GrosshadernMunichGermany

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