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Review article: Biomedical intelligence

Vol. 148 No. 1718 (2018)

The role of molecular imaging in assessing degenerative parkinsonism – an updated review

  • Nicolas Nicastro
  • Valentina Garibotto
  • Pierre R. Burkhard
DOI
https://doi.org/10.4414/smw.2018.14621
Cite this as:
Swiss Med Wkly. 2018;148:w14621
Published
26.04.2018

Summary

Diagnosing degenerative forms of parkinsonism still relies on a thorough clinical assessment, which in Parkinson’s disease involves the presence of an asymmetric bradykinesia with rest tremor and/or rigidity that respond substantially to levodopa. Conversely, atypical forms, including multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, exhibit additional features (cerebellar or pyramidal signs, early postural instability), a poor response to dopamine replacement therapy and a bad prognosis.

Consensus diagnostic criteria have excellent specificity, but lack sensitivity, and a clear diagnosis solely based on clinical evaluation is not always accurate, hence the need for diagnostic biomarkers. Nuclear medicine imaging is definitely one of them, allowing a qualitative and quantitative evaluation of in vivo functional integrity of monoaminergic (e.g., dopaminergic) pathways, brain metabolism and protein deposition and representing a unique window into these complex diseases. It has proved useful for early and accurate diagnosis, and possibly represents a valid biomarker of disease pathogenesis, progression and response to neuroprotective therapies.

This review focuses on the nigrostriatal pathway dysfunctions (demonstrated with presynaptic dopamine positron emission tomography [PET] and single photon emission computed tomography [SPECT] ligands) that confirm a degenerative form of parkinsonism. In addition, 123I-metaiodobenzylguanidine cardiac scintigraphy can unveil postganglionic autonomic failure specifically encountered in Parkinson’s disease. Brain 18F-fluorodeoxyglucose PET may also show a distinct hypometabolism for each degenerative form of parkinsonism. Since a few years ago, the proteins that aggregate in the brain of subjects with neurodegenerative diseases (tau and alpha-synuclein) can be evaluated in vivo by novel radioligands. These developments open new perspectives both as diagnostic tools and to understand the regional topography and burden of protein deposition on motor impairment and cognitive decline. The last part of the review proposes a strategic workup in the practical evaluation of a patient with parkinsonism.

References

  1. Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79(4):368–76. doi:.https://doi.org/10.1136/jnnp.2007.131045
  2. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9(1):357–81. doi:.https://doi.org/10.1146/annurev.ne.09.030186.002041
  3. Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990. Neurology. 1999;52(6):1214–20. doi:.https://doi.org/10.1212/WNL.52.6.1214
  4. Nakashita S, Wada-Isoe K, Uemura Y, Tanaka K, Yamamoto M, Yamawaki M, et al. Clinical assessment and prevalence of parkinsonism in Japanese elderly people. Acta Neurol Scand. 2016;133(5):373–9. doi:.https://doi.org/10.1111/ane.12472
  5. Stefanova N, Bücke P, Duerr S, Wenning GK. Multiple system atrophy: an update. Lancet Neurol. 2009;8(12):1172–8. doi:.https://doi.org/10.1016/S1474-4422(09)70288-1
  6. Richardson JC, Steele J, Olszewski J. Supranuclear Ophthalmoplegia, Pseudobulbar Palsy, Nuchal Dystonia and Dementia. A Clinical Report on Eight Cases of “Heterogenous System Degeneration”. Trans Am Neurol Assoc. 1963;88:25–9.
  7. Wenning GK, Litvan I, Jankovic J, Granata R, Mangone CA, McKee A, et al. Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination. J Neurol Neurosurg Psychiatry. 1998;64(2):184–9. doi:.https://doi.org/10.1136/jnnp.64.2.184
  8. Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord. 2000;15(3):503–10. doi:.https://doi.org/10.1002/1531-8257(200005)15:3<503::AID-MDS1013>3.0.CO;2-V
  9. Lorberboym M, Treves TA, Melamed E, Lampl Y, Hellmann M, Djaldetti R. [123I]-FP/CIT SPECT imaging for distinguishing drug-induced parkinsonism from Parkinson’s disease. Mov Disord. 2006;21(4):510–4. doi:.https://doi.org/10.1002/mds.20748
  10. Savica R, Grossardt BR, Bower JH, Ahlskog JE, Rocca WA. Incidence and pathology of synucleinopathies and tauopathies related to parkinsonism. JAMA Neurol. 2013;70(7):859–66. doi:.https://doi.org/10.1001/jamaneurol.2013.114
  11. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29(13):1583–90. doi:.https://doi.org/10.1002/mds.25945
  12. Ascherio A, Schwarzschild MA. The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol. 2016;15(12):1257–72. doi:.https://doi.org/10.1016/S1474-4422(16)30230-7
  13. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591–601. doi:.https://doi.org/10.1002/mds.26424
  14. Braak H, Tredici KD, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197–211. doi:.https://doi.org/10.1016/S0197-4580(02)00065-9
  15. Irwin DJ, White MT, Toledo JB, Xie SX, Robinson JL, Van Deerlin V, et al. Neuropathologic substrates of Parkinson disease dementia. Ann Neurol. 2012;72(4):587–98. doi:.https://doi.org/10.1002/ana.23659
  16. Garcia-Esparcia P, López-González I, Grau-Rivera O, García-Garrido MF, Konetti A, Llorens F, et al. Dementia with Lewy Bodies: Molecular Pathology in the Frontal Cortex in Typical and Rapidly Progressive Forms. Front Neurol. 2017;8:89. doi:.https://doi.org/10.3389/fneur.2017.00089
  17. Jellinger KA. Dementia with Lewy bodies and Parkinson’s disease-dementia: current concepts and controversies. J Neural Transm (Vienna). 2018;125(4):615–50.
  18. Petrou M, Dwamena BA, Foerster BR, MacEachern MP, Bohnen NI, Müller ML, et al. Amyloid deposition in Parkinson’s disease and cognitive impairment: a systematic review. Mov Disord. 2015;30(7):928–35. doi:.https://doi.org/10.1002/mds.26191
  19. Vekrellis K, Xilouri M, Emmanouilidou E, Rideout HJ, Stefanis L. Pathological roles of α-synuclein in neurological disorders. Lancet Neurol. 2011;10(11):1015–25. doi:.https://doi.org/10.1016/S1474-4422(11)70213-7
  20. Dickson DW. Parkinson’s disease and parkinsonism: neuropathology. Cold Spring Harb Perspect Med. 2012;2(8):a009258. doi:.https://doi.org/10.1101/cshperspect.a009258
  21. Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015;372(3):249–63. doi:.https://doi.org/10.1056/NEJMra1311488
  22. Coyle-Gilchrist IT, Dick KM, Patterson K, Vázquez Rodríquez P, Wehmann E, Wilcox A, et al. Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes. Neurology. 2016;86(18):1736–43. doi:.https://doi.org/10.1212/WNL.0000000000002638
  23. Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al.; Movement Disorder Society-endorsed PSP Study Group. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017;32(6):853–64. doi:.https://doi.org/10.1002/mds.26987
  24. Armstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80(5):496–503. doi:.https://doi.org/10.1212/WNL.0b013e31827f0fd1
  25. Heim B, Krismer F, De Marzi R, Seppi K. Magnetic resonance imaging for the diagnosis of Parkinson’s disease. J Neural Transm (Vienna). 2017;124(8):915–64. doi:.https://doi.org/10.1007/s00702-017-1717-8
  26. Kaasinen V, Vahlberg T. Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies. Ann Neurol. 2017;82(6):873–82. doi:.https://doi.org/10.1002/ana.25103
  27. Booij J, Tissingh G, Boer GJ, Speelman JD, Stoof JC, Janssen AG, et al. [123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1997;62(2):133–40. doi:.https://doi.org/10.1136/jnnp.62.2.133
  28. Benamer HTS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: The [123I]-FP-CIT study group. Mov Disord. 2000;15(3):503–10. doi:.https://doi.org/10.1002/1531-8257(200005)15:3<503::AID-MDS1013>3.0.CO;2-V
  29. Tinazzi M, Antonini A, Bovi T, Pasquin I, Steinmayr M, Moretto G, et al. Clinical and [123I]FP-CIT SPET imaging follow-up in patients with drug-induced parkinsonism. J Neurol. 2009;256(6):910–5. doi:.https://doi.org/10.1007/s00415-009-5039-0
  30. Brücke T, Asenbaum S, Pirker W, Djamshidian S, Wenger S, Wöber C, et al. Measurement of the dopaminergic degeneration in Parkinson’s disease with [123I] beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy. J Neural Transm Suppl. 1997;50:9–24. doi:.https://doi.org/10.1007/978-3-7091-6842-4_2
  31. Plotkin M, Amthauer H, Klaffke S, Kühn A, Lüdemann L, Arnold G, et al. Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. J Neural Transm (Vienna). 2005;112(5):677–92. doi:.https://doi.org/10.1007/s00702-004-0208-x
  32. Im JH, Chung SJ, Kim JS, Lee MC. Differential patterns of dopamine transporter loss in the basal ganglia of progressive supranuclear palsy and Parkinson’s disease: analysis with [(123)I]IPT single photon emission computed tomography. J Neurol Sci. 2006;244(1-2):103–9. doi:.https://doi.org/10.1016/j.jns.2006.01.006
  33. Nicastro N, Garibotto V, Badoud S, Burkhard PR. Scan without evidence of dopaminergic deficit: A 10-year retrospective study. Parkinsonism Relat Disord. 2016;31:53–8. doi:.https://doi.org/10.1016/j.parkreldis.2016.07.002
  34. Walker Z, Jaros E, Walker RW, Lee L, Costa DC, Livingston G, et al. Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J Neurol Neurosurg Psychiatry. 2007;78(11):1176–81. doi:.https://doi.org/10.1136/jnnp.2006.110122
  35. Antonini A, Benti R, De Notaris R, Tesei S, Zecchinelli A, Sacilotto G, et al. 123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Neurol Sci. 2003;24(3):149–50. doi:.https://doi.org/10.1007/s10072-003-0103-5
  36. Cilia R, Rossi C, Frosini D, Volterrani D, Siri C, Pagni C, et al. Dopamine Transporter SPECT Imaging in Corticobasal Syndrome. PLoS One. 2011;6(5):e18301. doi:.https://doi.org/10.1371/journal.pone.0018301
  37. Kaasinen V, Gardberg M, Röyttä M, Seppänen M, Päivärinta M. Normal dopamine transporter SPECT in neuropathologically confirmed corticobasal degeneration. J Neurol. 2013;260(5):1410–1. doi:.https://doi.org/10.1007/s00415-013-6886-2
  38. O’Sullivan SS, Burn DJ, Holton JL, Lees AJ. Normal dopamine transporter single photon-emission CT scan in corticobasal degeneration. Mov Disord. 2008;23(16):2424–6. doi:.https://doi.org/10.1002/mds.22323
  39. McKinley J, O’Connell M, Farrell M, Lynch T. Normal dopamine transporter imaging does not exclude multiple system atrophy. Parkinsonism Relat Disord. 2014;20(8):933–4. doi:.https://doi.org/10.1016/j.parkreldis.2014.04.022
  40. Nicastro N, Garibotto V, Burkhard PR. 123I-FP-CIT SPECT Accurately Distinguishes Parkinsonian From Cerebellar Variant of Multiple System Atrophy. Clin Nucl Med. 2018;43(2):e33–6.https://doi.org/10.1097/RLU.0000000000001477
  41. Benamer HT, Patterson J, Wyper DJ, Hadley DM, Macphee GJ, Grosset DG. Correlation of Parkinson’s disease severity and duration with 123I-FP-CIT SPECT striatal uptake. Mov Disord. 2000;15(4):692–8. doi:.https://doi.org/10.1002/1531-8257(200007)15:4<692::AID-MDS1014>3.0.CO;2-V
  42. Del Sole A, Perini G, Lecchi M, Mariani C, Lucignani G, Clerici F. Correlation between 123I-FP-CIT brain SPECT and parkinsonism in dementia with Lewy bodies: caveat for clinical use. Clin Nucl Med. 2015;40(1):32–5. doi:.https://doi.org/10.1097/RLU.0000000000000602
  43. Kraemmer J, Kovacs GG, Perju-Dumbrava L, Pirker S, Traub-Weidinger T, Pirker W. Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts. Mov Disord. 2014;29(14):1767–73. doi:.https://doi.org/10.1002/mds.25975
  44. Saari L, Kivinen K, Gardberg M, Joutsa J, Noponen T, Kaasinen V. Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease. Neurology. 2017;88(15):1461–7. doi:.https://doi.org/10.1212/WNL.0000000000003810
  45. Darcourt J, Booij J, Tatsch K, Varrone A, Vander Borght T, Kapucu OL, et al. EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled dopamine transporter ligands, version 2. Eur J Nucl Med Mol Imaging. 2010;37(2):443–50. doi:.https://doi.org/10.1007/s00259-009-1267-x
  46. Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, et al. In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease. Ann Neurol. 2000;47(4):493–503. doi:.https://doi.org/10.1002/1531-8249(200004)47:4<493::AID-ANA13>3.0.CO;2-4
  47. Frey KA. Can SPET imaging of dopamine uptake sites replace PET imaging in Parkinson’s disease? Against. Eur J Nucl Med Mol Imaging. 2002;29(5):715–7. doi:.https://doi.org/10.1007/s00259-002-0815-4
  48. Okamura N, Villemagne VL, Drago J, Pejoska S, Dhamija RK, Mulligan RS, et al. In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with (18)F-AV-133. J Nucl Med. 2010;51(2):223–8. doi:.https://doi.org/10.2967/jnumed.109.070094
  49. Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, et al., Parkinson Study Group. Levodopa and the progression of Parkinson’s disease. N Engl J Med. 2004;351(24):2498–508. doi:.https://doi.org/10.1056/NEJMoa033447
  50. Parkinson Study Group. A randomized controlled trial comparing pramipexole with levodopa in early Parkinson’s disease: design and methods of the CALM-PD Study. Clin Neuropharmacol. 2000;23(1):34–44. doi:.https://doi.org/10.1097/00002826-200001000-00007
  51. Parkinson Study Group PRECEPT Investigators. Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease. Neurology. 2007;69(15):1480–90. doi:.https://doi.org/10.1212/01.wnl.0000277648.63931.c0
  52. Marek K, Seibyl J, Eberly S, Oakes D, Shoulson I, Lang AE, et al.; Parkinson Study Group PRECEPT Investigators. Longitudinal follow-up of SWEDD subjects in the PRECEPT Study. Neurology. 2014;82(20):1791–7. doi:.https://doi.org/10.1212/WNL.0000000000000424
  53. Erro R, Schneider SA, Stamelou M, Quinn NP, Bhatia KP. What do patients with scans without evidence of dopaminergic deficit (SWEDD) have? New evidence and continuing controversies. J Neurol Neurosurg Psychiatry. 2016;87(3):319–23. doi:.https://doi.org/10.1136/jnnp-2014-310256
  54. Sixel-Döring F, Liepe K, Mollenhauer B, Trautmann E, Trenkwalder C. The role of 123I-FP-CIT-SPECT in the differential diagnosis of Parkinson and tremor syndromes: a critical assessment of 125 cases. J Neurol. 2011;258(12):2147–54. doi:.https://doi.org/10.1007/s00415-011-6076-z
  55. Nicastro N, Burkhard PR, Garibotto V. Scan without evidence of dopaminergic deficit (SWEDD) in degenerative parkinsonism and dementia with Lewy bodies: A prospective study. J Neurol Sci. 2018;385:17–21. doi:.https://doi.org/10.1016/j.jns.2017.11.039
  56. Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain. 2002;125(Pt 4):861–70. doi:.https://doi.org/10.1093/brain/awf080
  57. Schrag A, Ben-Shlomo Y, Quinn N. How valid is the clinical diagnosis of Parkinson’s disease in the community? J Neurol Neurosurg Psychiatry. 2002;73(5):529–34. doi:.https://doi.org/10.1136/jnnp.73.5.529
  58. Meyer PT, Hellwig S. Update on SPECT and PET in parkinsonism - part 1: imaging for differential diagnosis. Curr Opin Neurol. 2014;27(4):390–7. doi:.https://doi.org/10.1097/WCO.0000000000000106
  59. Eckert T, Barnes A, Dhawan V, Frucht S, Gordon MF, Feigin AS, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage. 2005;26(3):912–21. doi:.https://doi.org/10.1016/j.neuroimage.2005.03.012
  60. Zhao P, Zhang B, Gao S. 18F-FDG PET study on the idiopathic Parkinson’s disease from several parkinsonian-plus syndromes. Parkinsonism Relat Disord. 2012;18(Suppl 1):S60–2. doi:.https://doi.org/10.1016/S1353-8020(11)70020-7
  61. Juh R, Kim J, Moon D, Choe B, Suh T. Different metabolic patterns analysis of Parkinsonism on the 18F-FDG PET. Eur J Radiol. 2004;51(3):223–33. doi:.https://doi.org/10.1016/S0720-048X(03)00214-6
  62. Niethammer M, Tang CC, Feigin A, Allen PJ, Heinen L, Hellwig S, et al. A disease-specific metabolic brain network associated with corticobasal degeneration. Brain. 2014;137(Pt 11):3036–46. doi:.https://doi.org/10.1093/brain/awu256
  63. Antonini A, Schwarz J, Oertel WH, Beer HF, Madeja UD, Leenders KL. [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. 1994;44(7):1325–9. doi:.https://doi.org/10.1212/WNL.44.7.1325
  64. Brooks DJ, Ibanez V, Sawle GV, Playford ED, Quinn N, Mathias CJ, et al. Striatal D2 receptor status in patients with Parkinson’s disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography. Ann Neurol. 1992;31(2):184–92. doi:.https://doi.org/10.1002/ana.410310209
  65. Kim YJ, Ichise M, Ballinger JR, Vines D, Erami SS, Tatschida T, et al. Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov Disord. 2002;17(2):303–12. doi:.https://doi.org/10.1002/mds.10042
  66. Klaffke S, Kuhn AA, Plotkin M, Amthauer H, Harnack D, Felix R, et al. Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration. Mov Disord. 2006;21(10):1724–7. doi:.https://doi.org/10.1002/mds.21004
  67. Takatsu H, Nishida H, Matsuo H, Watanabe S, Nagashima K, Wada H, et al. Cardiac sympathetic denervation from the early stage of Parkinson’s disease: clinical and experimental studies with radiolabeled MIBG. J Nucl Med. 2000;41(1):71–7.
  68. Raffel DM, Koeppe RA, Little R, Wang CN, Liu S, Junck L, et al. PET measurement of cardiac and nigrostriatal denervation in Parkinsonian syndromes. J Nucl Med. 2006;47(11):1769–77.
  69. King AE, Mintz J, Royall DR. Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov Disord. 2011;26(7):1218–24. doi:.https://doi.org/10.1002/mds.23659
  70. Druschky A, Hilz MJ, Platsch G, Radespiel-Tröger M, Druschky K, Kuwert T, et al. Differentiation of Parkinson’s disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT. J Neurol Sci. 2000;175(1):3–12. doi:.https://doi.org/10.1016/S0022-510X(00)00279-3
  71. Südmeyer M, Antke C, Zizek T, Beu M, Nikolaus S, Wojtecki L, et al. Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach. J Nucl Med. 2011;52(5):733–40. doi:.https://doi.org/10.2967/jnumed.110.086959
  72. Berardelli A, Wenning GK, Antonini A, Berg D, Bloem BR, Bonifati V, et al. EFNS/MDS-ES/ENS recommendations for the diagnosis of Parkinson’s disease. Eur J Neurol. 2013;20(1):16–34. doi:.https://doi.org/10.1111/ene.12022
  73. Vlaar AM, de Nijs T, Kessels AG, Vreeling FW, Winogrodzka A, Mess WH, et al. Diagnostic value of 123I-ioflupane and 123I-iodobenzamide SPECT scans in 248 patients with parkinsonian syndromes. Eur Neurol. 2008;59(5):258–66. doi:.https://doi.org/10.1159/000115640
  74. Garibotto V, Montandon ML, Viaud CT, Allaoua M, Assal F, Burkhard PR, et al. Regions of interest-based discriminant analysis of DaTSCAN SPECT and FDG-PET for the classification of dementia. Clin Nucl Med. 2013;38(3):e112–7. doi:.https://doi.org/10.1097/RLU.0b013e318279b991
  75. Pilotto A, Premi E, Paola Caminiti S, Presotto L, Turrone R, Alberici A, et al. Single-subject SPM FDG-PET patterns predict risk of dementia progression in Parkinson disease. Neurology. 2018;90(12):e1029–37. doi:.https://doi.org/10.1212/WNL.0000000000005161
  76. Hellwig S, Amtage F, Kreft A, Buchert R, Winz OH, Vach W, et al. [18F]FDG-PET is superior to [123I]IBZM-SPECT for the differential diagnosis of parkinsonism. Neurology. 2012;79(13):1314–22. doi:.https://doi.org/10.1212/WNL.0b013e31826c1b0a
  77. Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol. 2003;106(6):518–26. doi:.https://doi.org/10.1007/s00401-003-0766-2
  78. Banati RB, Myers R, Kreutzberg GWPK. PK (‘peripheral benzodiazepine’)--binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to activated microglia. J Neurocytol. 1997;26(2):77–82. doi:.https://doi.org/10.1023/A:1018567510105
  79. Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis. 2006;21(2):404–12. doi:.https://doi.org/10.1016/j.nbd.2005.08.002
  80. Iannaccone S, Cerami C, Alessio M, Garibotto V, Panzacchi A, Olivieri S, et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord. 2013;19(1):47–52. doi:. Correction in: Parkinsomism Rel disord. 2013;19(10):921.https://doi.org/10.1016/j.parkreldis.2012.07.002
  81. Surendranathan A, Rowe JB, O’Brien JT. Neuroinflammation in Lewy body dementia. Parkinsonism Relat Disord. 2015;21(12):1398–406. doi:.https://doi.org/10.1016/j.parkreldis.2015.10.009
  82. Gerhard A, Banati RB, Goerres GB, Cagnin A, Myers R, Gunn RN, et al. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology. 2003;61(5):686–9. doi:.https://doi.org/10.1212/01.WNL.0000078192.95645.E6
  83. Gerhard A, Watts J, Trender-Gerhard I, Turkheimer F, Banati RB, Bhatia K, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration. Mov Disord. 2004;19(10):1221–6. doi:.https://doi.org/10.1002/mds.20162
  84. Kepe V, Bordelon Y, Boxer A, Huang SC, Liu J, Thiede FC, et al. PET imaging of neuropathology in tauopathies: progressive supranuclear palsy. J Alzheimers Dis. 2013;36(1):145–53.
  85. Marquié M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA, Rycyna LG, et al. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol. 2015;78(5):787–800. doi:.https://doi.org/10.1002/ana.24517
  86. Cho H, Choi JY, Hwang MS, Lee SH, Ryu YH, Lee MS, et al. Subcortical18F-AV-1451 binding patterns in progressive supranuclear palsy. Mov Disord. 2017;32(1):134–40. doi:.https://doi.org/10.1002/mds.26844
  87. Fodero-Tavoletti MT, Mulligan RS, Okamura N, Furumoto S, Rowe CC, Kudo Y, et al. In vitro characterisation of BF227 binding to alpha-synuclein/Lewy bodies. Eur J Pharmacol. 2009;617(1-3):54–8. doi:.https://doi.org/10.1016/j.ejphar.2009.06.042
  88. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al.; 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(15):2129–70. doi:.https://doi.org/10.1002/mds.22340
  89. Rosso AL, Bohnen NI, Launer LJ, Aizenstein HJ, Yaffe K, Rosano C. Vascular and dopaminergic contributors to mild parkinsonian signs in older adults. Neurology. 2018;90(3):e223–9. doi:.https://doi.org/10.1212/WNL.0000000000004842
  90. Ba F, Martin WR. Dopamine transporter imaging as a diagnostic tool for parkinsonism and related disorders in clinical practice. Parkinsonism Relat Disord. 2015;21(2):87–94. doi:.https://doi.org/10.1016/j.parkreldis.2014.11.007
  91. Berendse HW, Booij J, Francot CM, Bergmans PL, Hijman R, Stoof JC, et al. Subclinical dopaminergic dysfunction in asymptomatic Parkinson’s disease patients’ relatives with a decreased sense of smell. Ann Neurol. 2001;50(1):34–41. doi:.https://doi.org/10.1002/ana.1049
  92. Sommer U, Hummel T, Cormann K, Mueller A, Frasnelli J, Kropp J, et al. Detection of presymptomatic Parkinson’s disease: combining smell tests, transcranial sonography, and SPECT. Mov Disord. 2004;19(10):1196–202. doi:.https://doi.org/10.1002/mds.20141
  93. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670–6. doi:.https://doi.org/10.1212/01.wnl.0000324625.00404.15

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