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123I-FP-CIT SPECT findings and its clinical relevance in prodromal dementia with Lewy bodies

  • Koji Kasanuki
  • Eizo Iseki
  • Kazumi Ota
  • Daizo Kondo
  • Yosuke Ichimiya
  • Kiyoshi Sato
  • Heii Arai
Original Article

Abstract

Purpose

Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the 123I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance.

Methods

We enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer’s disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in 18F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of 123I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups.

Results

Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB.

Conclusion

123I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway.

Keywords

Dementia with Lewy bodies Early diagnosis 123I-FP-CIT SPECT Nigro-striatal dopaminergic pathway Olfactory dysfunction REM sleep behavior disorder 

Notes

Acknowledgments

None authors declare that they have conflicts of interest. The present study was supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology in Japan (grant number: 90648859).

References

  1. 1.
    McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65:1863–72.CrossRefPubMedGoogle Scholar
  2. 2.
    Chaudhuri KR, Martinez-Martin P, Schapira AH, et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study. Mov Disord. 2006;21:916–23.CrossRefPubMedGoogle Scholar
  3. 3.
    Chiba Y, Fujishiro H, Iseki E, et al. Retrospective survey of prodromal symptoms in dementia with Lewy bodies: comparison with Alzheimer's disease. Dement Geriatr Cogn Disord. 2012;33:273–81.CrossRefPubMedGoogle Scholar
  4. 4.
    Papathanasiou ND, Boutsiadis A, Dickson J, Bomanji JB. Diagnostic accuracy of 123I-FP-CIT (DaTSCAN) in dementia with Lewy bodies: a meta-analysis of published studies. Parkinsonism Relat Disord. 2012;18:225–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Fujishiro H, Iseki E, Kasanuki K, et al. Glucose hypometabolism in primary visual cortex is commonly associated with clinical features of dementia with Lewy bodies regardless of cognitive conditions. Int J Geriatr Psychiatr. 2012;27:1138–46.CrossRefGoogle Scholar
  6. 6.
    Petersen RC. Mild cognitive impairment as a diagnostic entity. J Int Med;256:183–194.Google Scholar
  7. 7.
    McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Scheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal lobes on MRI in ‘probable’ Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992;55:967–72.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Fazekas F, Kleinert R, Offenbacher H, et al. The morphologic correlate of incidental punctate white matter hyperintensities on MR images. Am J Neuroradiol. 1991;12:915–21.PubMedGoogle Scholar
  10. 10.
    E. Iseki, N. Murayama, R. Yamamoto, H, et al. Construction of a (18)F-FDG PET normative database of Japanese healthy elderly subjects and its application to demented and mild cognitive impairment patients. Int J Geriatr Psychiatry. 2010; 25: 352–361.Google Scholar
  11. 11.
    Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE. A diagnostic approach in Alzheimer’s disease using three-dimensional Stereotactic surface projections of Fluorine-19-FDG PET. J Nucl Med. 1995;36:1238–48.PubMedGoogle Scholar
  12. 12.
    Mizumura S, Kumita S, Cho K, et al. Development of quantitative analysis method for stereotactic brain image: assessment of reduced accumulation in extent and severity using anatomical segmentation. Ann Nucl Med. 2003;17:289–95.CrossRefPubMedGoogle Scholar
  13. 13.
    Japanese society of nuclear medicine. Japanese ioflupane guideline working group recommendation. http://www.jsnm.org/guideline/ioflupane. Accessed 3 Jun 2016.
  14. 14.
    Kuya K, Shinohara Y, Miyoshi F, Fujii S, Tanabe Y, Ogawa T. Correlation between neuromelanin-sensitive MR imaging and 123I-FP-CIT SPECT in patients with parkinsonism. Neuroradiology. 2016;58:351–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Dickson JC, Tossici-Bolt L, Sera T, et al. The impact of reconstruction method on the quantification of DaTSCAN images. Eur J Nucl Med Mol Imaging. 2010;37:23–35.CrossRefPubMedGoogle Scholar
  16. 16.
    Tossici-Bolt L, Hoffmann SM, Kemp PM, Mehta RL, Fleming JS. Quantification of [123I] FP-CIT SPECT brain images: an accurate technique for measurement of the specific binding ratio. Eur J Nucl Med Mol Imaging. 2006;33:1491–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Boeve BF. REM sleep behavior disorder: Updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci. 2010;1184:15–54.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tolosa E, Borght TV, Moreno E. Accuracy of DaTSCAN (123I-Ioflupane) SPECT in diagnosis of patients with clinically uncertain parkinsonism: 2-year follow-up of an open-label study. Mov Disord. 2007;22:2346–51.CrossRefPubMedGoogle Scholar
  19. 19.
    Siepel FJ, Rongve A, Buter TC, et al. FP-CIT SPECT in suspected dementia with Lewy bodies: A longitudinal case study. BMJ Open. 123I. doi: 10.1136/bmjopen-2013-002642.
  20. 20.
    Fujishiro H, Iseki E, Murayama N, et al. Diffuse occipital hypometabolism on [18F]-FDG PET scans in patients with idiopathic REM sleep behavior disorder: Prodomal dementia with Lewy bodies? Psychogeriatrics. 2010;10:144–52.CrossRefPubMedGoogle Scholar
  21. 21.
    Fujishiro H, Iseki E, Kasanuki K, et al. A follow up study of non-demented patients with primary visual cortical hypometabolism: prodromal dementia with Lewy bodies. J Neurol Sci. 2013;334:48–54.CrossRefPubMedGoogle Scholar
  22. 22.
    Bohnen NI, Koeppe RA, Minoshima S, et al. Cerebral glucose metabolic features of Parkinson disease and incident dementia: longitudinal study. J Nucl Med. 2011;52:848–55.CrossRefPubMedGoogle Scholar
  23. 23.
    Booij J, Tissingh G, Boer GJ, 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 Psych. 1997;62:133–40.CrossRefGoogle Scholar
  24. 24.
    Rektorova I, Srovnalova H, Kubikova R, Prasek J. Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson’s disease. Mov Disord. 2008;23:1580–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain. 2005;128:1314–22.CrossRefPubMedGoogle Scholar
  26. 26.
    Burruss JW, Hurley RA, Taber KH, Rauch RA, Norton RE, Hayman LA. Functional neuroanatomy of the frontal lobe circuits. Radiology. 2000;214:227–30.CrossRefPubMedGoogle Scholar
  27. 27.
    Ziebell M, Andersen BB, Pinborg LH, et al. Striatal dopamine transporter binding does not correlate with clinical severity in dementia with Lewy bodies. J Nucl Med. 2013;54:1072–6.CrossRefPubMedGoogle Scholar
  28. 28.
    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;40:32–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Roselli F, Pisciotta NM, Perneczky R, et al. Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: A 123I-FP-CIT SPECT study. Mov Disord. 2009;24:2097–103.CrossRefPubMedGoogle Scholar
  30. 30.
    Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24:197–211.CrossRefPubMedGoogle Scholar
  31. 31.
    Marsden CD. Parkinson’s disease. Lancet. 1990;335:948–52.CrossRefPubMedGoogle Scholar
  32. 32.
    Attems J, Quass M, Jellinger KA. Tau and alpha-synuclein brainstem pathology in Alzheimer disease: relation with extrapyramidal signs. Acta Neuropathol. 2007;113:53–62.CrossRefPubMedGoogle Scholar
  33. 33.
    Walker Z, Jaros E, Walker RW, 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;78:1176–81.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Taylor JP, Colloby SJ, McKeith IG, et al. Cholinesterase inhibitor use does not significantly influence the ability of 123I-FP-CIT imaging to distinguish Alzheimer’s disease from dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2007;78:1069–71.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA. 2002;287:1653–61.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Koji Kasanuki
    • 1
    • 2
    • 3
  • Eizo Iseki
    • 1
    • 2
  • Kazumi Ota
    • 1
    • 2
  • Daizo Kondo
    • 1
  • Yosuke Ichimiya
    • 2
  • Kiyoshi Sato
    • 1
  • Heii Arai
    • 2
  1. 1.PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical CenterJuntendo University School of MedicineTokyoJapan
  2. 2.Department of PsychiatryJuntendo University School of MedicineTokyoJapan
  3. 3.Department of NeuroscienceMayo ClinicJacksonvilleUSA

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