Dement Geriatr Cogn Disord 2008;25:195–205
(DOI:10.1159/000113417)

Early Discriminatory Diagnosis of Dementia with Lewy Bodies

The Emerging Role of CSF and Imaging Biomarkers

Aarsland D.a, c · Kurz M.a · Beyer M.b · Bronnick K.a · Piepenstock Nore S.d · Ballard C.e
aNorwegian Centre for Movement Disorders and bDepartment of Radiology, Stavanger University Hospital, Stavanger, and cInstitute of Clinical Medicine, University of Bergen, and dGeriatric section, Haraldsplass Deaconess University Hospital, Bergen, Norway; eWolfson Centre for Age-Related Diseases, King’s College London, London, UK
email Corresponding Author


 goto top of outline Key Words

  • Dementia with Lewy bodies, early diagnosis
  • Cerebrospinal fluid
  • Imaging biomarkers

 goto top of outline Abstract

Background: The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer’s disease (AD). Method: We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB. Results: The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid β (aβ) isoforms as well as α-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level. Conclusion: Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.

Copyright © 2008 S. Karger AG, Basel


 goto top of outline References
  1. McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda JE, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez OL, Carlos Machado J, O’Brien J, Playfer J, Reid W; International Psychogeriatric Association Expert Meeting on DLB: Dementia with Lewy bodies. Lancet Neurol 2004;3:19–28.
  2. Wakisaka Y, Furuta A, Tanizaki Y, Kiyohara Y, Iida M, Iwaki T: Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study. Acta Neuropathol 2003;106:374–382.
  3. Zaccai J, McCracken C, Brayne C: A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age Ageing 2005;34:561–566.
  4. Lippa CF, Duda JF, Grossman M, Hurtig HI, Aarsland D, Boeve BF, Brooks DJ, Dickson DW, Dubois B, Emre M, Fahn S, Farmer JM, Galasko D, Galvin JE, Goetz CG, Growdon JH, Gwinn-Hardy KA, Hardy J, Heutink P, Iwatsubo T, Kosaka K, Lee VM, Leverenz JB, Masliah E, McKeith IG, Nussbaum RL, Olanow CW, Ravina BM, Singleton AB, Tanner CM, Trojanowski JQ, Wszolek ZK; DLB/PDD Working Group: DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 2007;68:812–819.
  5. Aarsland D, Zaccai J, Brayne C: A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord 2005;20:1255–1263.
  6. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996;47:1113–1124.
  7. McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M; Consortium on DLB: Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005;65:1863–1872.
  8. Mega MS, Masterman DL, Benson DF, Vinters HV, Tomiyasu U, Craig AH, Foti DJ, Kaufer D, Scharre DW, Fairbanks L, Cummings JL: Dementia with Lewy bodies: reliability and validity of clinical and pathologic criteria. Neurology 1996;47:1403–1409.
  9. Ferman TJ, Smith GE, Boeve BF, Ivnik RJ, Petersen RC, Knopman D, Graff-Radford N, Parisi J, Dickson DW: DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging. Neurology 2004;62:181–187.
  10. Fahn S, Elton RL; UPDRS Development Committee: Unified Parkinson’s Disease Rating Scale; in Fahn S, Marsden CD, Calne DB, Goldstein M (eds): Recent developments in Parkinson’s disease. Florham Park, Macmillan Health Care Information, 1987, vol 2, pp 153–164.
  11. Richards M, Marder K, Bell K, Dooneief G, Mayeux R, Stern Y: Interrater reliability of extrapyramidal signs in a group assessed for dementia. Arch Neurol 1991;48:1147–1149.
  12. Ballard C, McKeith I, Burn D, Harrison R, O’Brien J, Lowery K, Campbell M, Perry R, Ince P: The UPDRS scale as a means of identifying extrapyramidal signs in patients suffering from dementia with Lewy bodies. Acta Neurol Scand 1997;96:366–371.
  13. Ballard CG, Jacoby R, Del Ser T, Khan MN, Munoz DG, Holmes C, Nagy Z, Perry EK, Joachim C, Jaros E, O’Brien JT, Perry RH, McKeith IG: Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with lewy bodies. Am J Psychiatry 2004;161:843–849.
  14. Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B; EFNS: Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol 2007;14:e1–e26.
  15. McKeith I, Fairbairn A, Perry R, Thompson P, Perry E: Neuroleptic sensitivity in patients with senile dementia of Lewy body type. BMJ 1992;305:673–678.
  16. Aarsland D, Perry R, Larsen JP, McKeith IG, O’Brien JT, Perry EK, Burn D, Ballard CG: Neuroleptic sensitivity in Parkinson’s disease and parkinsonian dementias. J Clin Psychiatry 2005;66:633–637.
  17. Molloy SA, Rowan EN, O’Brien JT, McKeith IG, Wesnes K, Burn DJ: Effect of levodopa on cognitive function in Parkinson’s disease with and without dementia and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2006;77:1323–1328.
  18. McKeith IG, Rowan E, Askew K, Naidu A, Allan L, Barnett N, Lett D, Mosimann UP, Burn D, O’Brien JT: More severe functional impairment in dementia with Lewy bodies than Alzheimer disease is related to extrapyramidal motor dysfunction. Am J Geriatr Psychiatry 2006;14:582–588.
  19. Bostrom FMP, Jonsson L, Minthon L, Londos E: Patients with dementia with Lewy bodies have more impaired quality of life than patients with Alzheimer’s disease. Neurodegener Dis 2007;4:127.

    External Resources

  20. Williams MM, Xiong C, Morris JC, Galvin JE: Survival and mortality differences between dementia with Lewy bodies vs. Alzheimer disease. Neurology 2006;67:1935–1941.
  21. Bostrom F, Jonsson L, Minthon L, Londos E: Patients with Lewy body dementia use more resources than those with Alzheimer’s disease. Int J Geriatr Psychiatry 2006, E-pub ahead of print. DOI: 10.1002/gps.1738.
  22. McNaught KS, Perl DP, Brownell AL, Olanow CW: Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease. Ann Neurol 2004;56:149–162.
  23. Crystal HA, Dickson DW, Lizardi JE, Davies P, Wolfson LI: Antemortem diagnosis of diffuse Lewy body disease. Neurology 1990;40:1523–1528.
  24. Calzetti S, Bortone E, Negrotti A, Zinno L, Mancia D: Frontal intermittent rhythmic delta activity (FIRDA) in patients with dementia with Lewy bodies: a diagnostic tool? Neurol Sci 2002;23(suppl 2):S65–S66.
  25. Briel RC, McKeith IG, Barker WA, Hewitt Y, Perry RH, Ince PG, Fairbairn AF: EEG findings in dementia with Lewy bodies and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1999;66:401–403.
  26. Barber PA, Varma AR, Lloyd JJ, Haworth B, Snowden JS, Neary D: The electroencephalogram in dementia with Lewy bodies. Acta Neurol Scand 2000;101:53–56.
  27. Londos E, Passant U, Brun A, Rosén I, Risberg J, Gustafson L: Regional cerebral blood flow and EEG in clinically diagnosed dementia with Lewy bodies and Alzheimer’s disease. Arch Gerontol Geriatr 2003;36:231–245.
  28. Kai T, Asai Y, Sakuma K, Koeda T, Nakashima K: Quantitative electroencephalogram analysis in dementia with Lewy bodies and Alzheimer’s disease. J Neurol Sci 2005;237:89–95.
  29. Walker MP, Ayre GA, Perry EK, Wesnes K, McKeith IG, Tovee M, Edwardson JA, Ballard CG: Quantification and characterization of fluctuating cognition in dementia with Lewy bodies and Alzheimer’s disease. Dement Geriatr Cogn Disord 2000;11:327–335.
  30. Walker MP, Ayre GA, Cummings JL, Wesnes K, McKeith IG, O’Brien JT, Ballard CG: Quantifying fluctuation in dementia with Lewy bodies, Alzheimer’s disease, and vascular dementia. Neurology 2000;54:1616–1625.
  31. Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A: Genetics of Parkinson’s disease and parkinsonism. Ann Neurol 2006;60:389–398.
  32. Blennow K, de Leon MJ, Zetterberg H: Alzheimer’s disease. Lancet 2006;368:387–403.
  33. Kurz MW, Larsen JP, Kvaloy JT, Aarsland D: Associations between family history of Parkinson’s disease and dementia and risk of dementia in Parkinson’s disease: a community-based, longitudinal study. Mov Disord 2006;21:2170–2174.
  34. Woodruff BK, Graff-Radford NR, Ferman TJ, Dickson DW, DeLucia MW, Crook JE, Arvanitakis Z, Brassler S, Waters C, Barker W, Duara R: Family history of dementia is a risk factor for Lewy body disease. Neurology 2006;66:1949–1950.
  35. McKeith IG: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis 2006;9:417–423.

    External Resources

  36. Aarsland D, Perry R, Brown A, Larsen JP, Ballard C: Neuropathology of dementia in Parkinson’s disease: a prospective, community-based study. Ann Neurol 2005;58:773–776.
  37. Wszolek ZK, Pfeiffer RF, Tsuboi Y, Uitti RJ, McComb RD, Stoessl AJ, Strongosky AJ, Zimprich A, Müller-Myhsok B, Farrer MJ, Gasser T, Calne DB, Dickson DW: Autosomal dominant parkinsonism associated with variable synuclein and tau pathology. Neurology 2004;62:1619–1622.
  38. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Müller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T: Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 2004;44:601–607.
  39. Berg D, Schweitzer K, Leitner P, Zimprich A, Lichtner P, Belcredi P, Brussel T, Schulte C, Maass S, Nagele T: Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson’s disease. Brain 2005;128:3000–3011.

    External Resources

  40. Zhu X, Babar A, Siedlak SL, Yang Q, Ito G, Iwatsubo T, Smith MA, Perry G, Chen SG: LRRK2 in Parkinson’s disease and dementia with Lewy bodies. Mol Neurodegener 2006;1:17.

    External Resources

  41. Mayeux R, Saunders AM, Shea S, Mirra S, Evans D, Roses AD, Hyman BT, Crain B, Tang MX, Phelps CH; Alzheimer’s Disease Centers Consortium on Apolipoprotein E and Alzheimer’s Disease: Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. N Engl J Med 1998;338:506–511.
  42. Borroni B, Grassi M, Costanzi C, Archetti S, Caimi L, Padovani A: APOE genotype and cholesterol levels in Lewy body dementia and Alzheimer disease: investigating genotype-phenotype effect on disease risk. Am J Geriatr Psychiatry 2006;14:1022–1031.
  43. Singleton AB, Wharton A, O’Brien KK, Walker MP, McKeith IG, Ballard CG, O’Brien J, Perry RH, Ince PG, Edwardson JA, Morris CM: Clinical and neuropathological correlates of apolipoprotein E genotype in dementia with Lewy bodies. Dement Geriatr Cogn Disord 2002;14:167–175.
  44. Engelborghs S, Dermaut B, Goeman J, Saerens J, Mariën P, Pickut BA, Van den Broeck M, Serneels S, Cruts M, Van Broeckhoven C, De Deyn PP: Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects. J Neurol Neurosurg Psychiatry 2003;74:1148–1151.
  45. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L: Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006;5:228–234.
  46. Gómez-Tortosa E, Gonzalo I, Fanjul S, Sainz MJ, Cantarero S, Cemillán C, Yébenes JG, del Ser T: Cerebrospinal fluid markers in dementia with Lewy bodies compared with Alzheimer disease. Arch Neurol 2003;60:1218–1222.
  47. Vanderstichele H, De Vreese K, Blennow K, Andreasen N, Sindic C, Ivanoiu A, Hampel H, Bürger K, Parnetti L, Lanari A, Padovani A, DiLuca M, Bläser M, Olsson AO, Pottel H, Hulstaert F, Vanmechelen E: Analytical performance and clinical utility of the INNOTEST PHOSPHO-TAU181P assay for discrimination between Alzheimer’s disease and dementia with Lewy bodies. Clin Chem Lab Med 2006;44:1472–1480.
  48. Bibl M, Mollenhauer B, Esselmann H, Lewczuk P, Klafki HW, Sparbier K, Smirnov A, Cepek L, Trenkwalder C, Rüther E, Kornhuber J, Otto M, Wiltfang J: CSF amyloid-beta-peptides in Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease dementia. Brain 2006;129:1177–1187.
  49. Bibl M, Mollenhauer B, Lewczuk P, Esselmann H, Wolf S, Trenkwalder C, Otto M, Stiens G, Rüther E, Kornhuber J, Wiltfang J: Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias. Mol Psychiatry 2007;12:671–680.
  50. Clark CM, Xie S, Chittams J, Ewbank D, Peskind E, Galasko D, Morris JC, McKeel DW, Farlow M, Weitlauf SL, Quinn J, Kaye J, Knopman D, Arai H, Doody RS, De Carli C, Leight S, Lee VM, Trojanowski JQ: Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses? Arch Neurol 2003;60:1696–1702.
  51. Mollenhauer B, Cepek L, Bibl M, Wiltfang J, Schulz-Schaeffer WJ, Ciesielczyk B, Neumann M, Steinacker P, Kretzschmar HA, Poser S, Trenkwalder C, Otto M: Tau protein, Abeta42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies. Dement Geriatr Cogn Disord 2005;19:164–170.
  52. Mollenhauer B, Bibl M, Wiltfang J, Steinacker P, Ciesielczyk B, Neubert K, Trenkwalder C, Otto M: Total tau protein, phosphorylated tau (181p) protein, beta- amyloid(1–42), and beta-amyloid(1–40) in cerebrospinal fluid of patients with dementia with Lewy bodies. Clin Chem Lab Med 2006;44:192–195.
  53. El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, Court JA, Schlossmacher MG, Allsop D: 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.
  54. Tokuda T, Salem SA, Allsop D, Mizuno T, Nakagawa M, Qureshi MM, Locascio JJ, Schlossmacher MG, El-Agnaf OM: Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s disease. Biochem Biophys Res Commun 2006;349:162–166.
  55. Mollenhauer B, Trenkwalder C, Cullen V, Krastins, B, Kahn I, El-Agnaf OAA, Locascio JJ, Kretzchmar HA, Sarracino D, Von Sattel JP, Schlossmacher MG: A platform for the quantification of alpha-synuclein in cerebrospinal fluid: evidence for a potential biomarker for synucleinopathies. Neurodegener Dis 2007;4:156.

    External Resources

  56. Schlossmacher MG: Quantification of alpha-synuclein in dopamine cells, peripheral blood, genotyped brain and CSF. Neurodegener Dis 2007;4:187.
  57. Shukla R, Rajani M, Srivastava N, Barthwal MK, Dikshit M: Nitrite and malondialdehyde content in cerebrospinal fluid of patients with Parkinson’s disease. Int J Neurosci 2006;116:1391–1402.
  58. Waragai M, Wei J, Fujita M, Nakai M, Ho GJ, Masliah E, Akatsu H, Yamada T, Hashimoto MW: Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson’s disease. Biochem Biophys Res Comm 2006;345:967–972.
  59. Isobe C, Murata T, Sato C, Terayama Y: Increase of total homocysteine concentration in cerebrospinal fluid in patients with Alzheimer’s disease and Parkinson’s disease. Life Sci 2005;77:1836–1843.
  60. Hashimoto M, Rockenstein E, Crews L, Masliah E: Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases. Neuromolecular Med 2003;4:21–36.
  61. Hyun DH, Lee M, Halliwell B, Jenner P: Proteasomal inhibition causes the formation of protein aggregates containing a wide range of proteins, including nitrated proteins. J Neurochem 2003;86:363–373.
  62. Abdi F, Quinn JF, Jankovic J, McIntosh M, Leverenz JB, Peskind E, Nixon R, Nutt J, Chung K, Zabetian C, Samii A, Lin M, Hattan S, Pan C, Wang Y, Jin J, Zhu D, Li GJ, Liu Y, Waichunas D, Montine TJ, Zhang J: Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J Alzheimer Dis 2006;9:293–348.
  63. Gao FQ, Black SE, Leibovitch FS, Callen DJ, Rockel CP, Szalai JP: Linear width of the medial temporal lobe can discriminate Alzheimer’s disease from normal aging: the Sunnybrook dementia study. Neurobiol Aging 2004;25:441–448.
  64. Burton EJ, Karas G, Paling SM, Barber R, Williams ED, Ballard CG, McKeith IG, Scheltens P, Barkhof F, O’Brien JT: Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry. Neuroimage 2002;17:618–630.
  65. Barber R, Gholkar A, Scheltens P, Ballard C, McKeith IG, O’Brien JT: Medial temporal lobe atrophy on MRI in dementia with Lewy bodies. Neurology 1999;52:1153–1158.
  66. Barber R, Ballard C, McKeith IG, Gholkar A, O’Brien JT: MRI volumetric study of dementia with Lewy bodies: a comparison with AD and vascular dementia. Neurology 2000;54:1304–1309.
  67. Cousins DA, Burton EJ, Burn D, Gholkar A, McKeith IG, O’Brien JT: Atrophy of the putamen in dementia with Lewy bodies but not Alzheimer’s disease: an MRI study. Neurology 2003;61:1191–1195.
  68. Brenneis C, Wenning GK, Egger KE, Schocke M, Trieb T, Seppi K, Marksteiner J, Ransmayr G, Benke T, Poewe W: Basal forebrain atrophy is a distinctive pattern in dementia with Lewy bodies. Neuroreport 2004;15:1711–1714.
  69. Hanyu H, Shimizu S, Tanaka Y, Hirao K, Iwamoto T, Abe K: MR features of the substantia innominata and therapeutic implications in dementias. Neurobiol Aging 2007;28:548–554.
  70. O’Brien JT, Paling S, Barber R, Williams ED, Ballard C, McKeith IG, Gholkar A, Crum WR, Rossor MN, Fox NC: Progressive brain atrophy on serial MRI in dementia with Lewy bodies, AD, and vascular dementia. Neurology 2001;56:1386–1388.
  71. Whitwell JL, Weigand SD, Shiung MM, Boeve BF, Ferman TJ, Smith GE, Knopman DS, Petersen RC, Benarroch EE, Josephs KA, Jack CR: Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer’s disease. Brain 2007;130:708–719.
  72. Lobotesis K, Fenwick JD, Phipps A, Ryman A, Swann A, Ballard C, McKeith IG, O’Brien JT: Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD. Neurology 2001;56:643–649.
  73. Shimizu S, Hanyu H, Kanetaka H, Iwamoto T, Koizumi K, Abe K: Differentiation of dementia with Lewy bodies from Alzheimer’s disease using brain SPECT. Dement Geriatr Cogn Disord 2005;20:25–30.
  74. Hanyu H, Shimizu S, Hirao K, Kanetaka H, Sakurai H, Iwamoto T, Koizumi K, Abe K: Differentiation of dementia with Lewy bodies from Alzheimer’s disease using Mini-Mental State Examination and brain perfusion SPECT. J Neurol Sci 2006;250:97–102.
  75. Kemp PM, Hoffmann SA, Tossici-Bolt L, Fleming JS, Holmes C: Limitations of the HMPAO SPECT appearances of occipital lobe perfusion in the differential diagnosis of dementia with Lewy bodies. Nucl Med Commun 2007;28:451–456.
  76. Kemp PM, Holmes C: Imaging in dementia with Lewy bodies: a review. Nucl Med Commun 2007;28:511–519.
  77. Allan LM, Ballard CG, Allen J, Murray A, Davidson AW, McKeith IG, Kenny RA: Autonomic dysfunction in dementia. J Neurol Neurosurg Psychiatry 2007;78:671–677.
  78. Orimo S, Amino T, Itoh Y, Takahashi A, Kojo T, Uchihara T, Tsuchiya K, Mori F, Wakabayashi K, Takahashi H: Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol (Berl) 2005;109:583–588.
  79. Spiegel J, Möllers MO, Jost WH, Fuss G, Samnick S, Dillmann U, Becker G, Kirsch CM: FP-CIT and MIBG scintigraphy in early Parkinson’s disease. Mov Disord 2005;20:552–561.
  80. Watanabe H, Ieda T, Katayama T, Takeda A, Aiba I, Doyu M, Hirayama M, Sobue G: Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2001;70:781–783.
  81. Yoshita M, Taki J, Yamada M: A clinical role for [123I]MIBG myocardial scintigraphy in the distinction between dementia of the Alzheimer type and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2001;71:583–588.
  82. Oide T, Tokuda T, Momose M, Oguchi K, Nakamura A, Ohara S, Ikeda S: Usefulness of [123I]metaiodobenzylguanidine ([123I]MIBG) myocardial scintigraphy in differentiating between Alzheimer’s disease and dementia with Lewy bodies. Intern Med 2003;42:686–690.
  83. Jindahra P, Vejjajiva A, Witoonpanich R, Sirisriro R, Sritara C, Pulkes T: Differentiation of dementia with Lewy bodies, Alzheimer’s disease and vascular dementia by cardiac 131I-meta-iodobenzylguanidine (MIBG) uptake (preliminary report). J Med Assoc Thai 2004;87:1176–1181.

    External Resources

  84. Yoshita M, Taki J, Yokoyama K, Noguchi-Shinohara M, Matsumoto Y, Nakajima K, Yamada M: Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD. Neurology 2006;66:1850–1854.
  85. Kashihara K, Ohno M, Kawada S, Okumura Y: Reduced cardiac uptake and enhanced washout of 123I-MIBG in pure autonomic failure occurs conjointly with Parkinson’s disease and dementia with Lewy bodies. J Nucl Med 2006;47:1099–1101.
  86. Hanyu H, Shimizu S, Hirao K, Sakurai H, Iwamoto T, Chikamori T, Hida S, Yamashina A, Koizumi K, Abe K: The role of 123I-metaiodobenzylguanidine myocardial scintigraphy in the diagnosis of Lewy body disease in patients with dementia in a memory clinic. Dement Geriatr Cogn Disord 2006;22:379–384.
  87. Hanyu H, Shimizu S, Hirao K, Kanetaka H, Iwamoto T, Chikamori T, Usui Y, Yamashina A, Koizumi K, Abe K: Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2006;33:248–253.
  88. Suzuki M, Kurita A, Hashimoto M, Fukumitsu N, Abo M, Ito Y, Urashima M, Inoue K: Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson’s disease. J Neurol Sci 2006;240:15–19.
  89. Wada-Isoe K, Kitayama M, Nakaso K, Nakashima K: Diagnostic markers for diagnosing dementia with Lewy bodies: CSF and MIBG cardiac scintigraphy study. J Neurol Sci 2007;260:33–37.
  90. Oka H, Morita M, Onouchi K, Yoshioka M, Mochio S, Inoue K: Cardiovascular autonomic dysfunction in dementia with Lewy bodies and Parkinson’s disease. J Neurol Sci 2007;254:72–77.
  91. Yoshita M, Yamada M: Occipital cerebral hypoperfusion and cardiac sympathetic dysfunction in dementia with Lewy bodies and dementia of the Alzheimer type. Neurology 2003;60:A208.

    External Resources

  92. Piggott MA, Marshall EF, Thomas N, Lloyd S, Court JA, Jaros E, Burn D, Johnson M, Perry RH, McKeith IG, Ballard C, Perry EK: Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer’s and Parkinson’s diseases: rostrocaudal distribution. Brain 1999;122:1449–1468.
  93. Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, Speelman JD, Horstink MH, Sips HJ, Dierckx RA, Versijpt J, Decoo D, Van Der Linden C, Hadley DM, Doder M, Lees AJ, Costa DC, Gacinovic S, Oertel WH, Pogarell O, Hoeffken H, Joseph K, Tatsch K, Schwarz J, Ries V: 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;15:503–510.
  94. O’Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn D, Aarsland D, McKeith IG: Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol 2004;61:919–925.
  95. Walker Z, Costa DC, Walker RW, Shaw K, Gacinovic S, Stevens T, Livingston G, Ince P, McKeith IG, Katona CL: Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry 2002;73:134–140.
  96. Donnemiller E, Heilmann J, Wenning GK, Berger W, Decristoforo C, Moncayo R, Poewe W, Ransmayr G: Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT single-photon emission tomography in dementia of the Alzheimer type and diffuse Lewy body disease. Eur J Nucl Med 1997;24:320–325.
  97. Walker Z, Jaros E, Walker RW, Lee L, Costa DC, Livingston G, Ince P, Perry R, McKeith I, Katona CL: Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT SPECT imaging and autopsy. J Neurol Neurosurg Psychiatry 2007;78:1176–1181.
  98. Colloby SJ, Williams ED, Burn DJ, Lloyd JJ, McKeith IG, O’Brien JT: Progression of dopaminergic degeneration in dementia with Lewy bodies and Parkinson’s disease with and without dementia assessed using 123I-FP-CIT SPECT. Eur J Nucl Med Mol Imaging 2005;32:1176–1185.
  99. McKeith I, O’Brien J, Walker Z, Tatsch K, Booij J, Darcourt J, Padovani A, Giubbini R, Bonuccelli U, Volterrani D, Holmes C, Kemp P, Tabet N, Meyer I, Reininger C; DLB Study Group: Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol 2007;6:305–313.
  100. Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group: Consensus report of the Working Group on: Molecular and Biochemical Markers of Alzheimer’s Disease. Neurobiol Aging 1998;19:109–116.

 goto top of outline Author Contacts

Dag Aarsland
Stavanger University Hospital
Arm Hansen v 20
NO–4005 Stavanger (Norway)
Tel. +47 5151 5062, Fax +47 5151 5195, E-Mail daarsland@gmail.com


 goto top of outline Article Information

Accepted: October 21, 2007
Published online: January 17, 2008
Number of Print Pages : 11
Number of Figures : 0, Number of Tables : 1, Number of References : 100


 goto top of outline Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 25, No. 3, Year 2008 (Cover Date: March 2008)

Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420–8008 (Print), eISSN: 1421–9824 (Online)

For additional information: http://www.karger.com/DEM


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