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Cingulate island sign on FDG-PET is associated with medial temporal lobe atrophy in dementia with Lewy bodies

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Abstract

Objective

The cingulate island sign (CIS), which refers to sparing of the posterior cingulate relative to the precuneus and cuneus, has been proposed as an FDG-PET imaging feature of dementia with Lewy bodies (DLB). The sign is reportedly associated with Alzheimer’s disease (AD) type neurofibrillary tangle (NFT) pathology in autopsy cases. To confirm this relationship using neuroimaging modalities in vivo, we investigated associations between CIS and the medial temporal lobe (MTL) atrophy in DLB.

Methods

Twenty-four patients each of DLB and AD underwent both 18F-FDG-PET and MRI with voxel-based morphometry. Dopamine transporter (DAT) density was also measured by DAT-SPECT in all those with DLB and in five with AD. The accumulation of FDG in the posterior cingulate ROI was divided by that in the precuneus plus cuneus ROI to derive the CIS ratio from the FDG-PET images. Values for cognitive function of Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Ray Auditory Verbal Learning Test (RAVLT) and scores for the core-feature triad of fluctuation, hallucination and parkinsonism were also statistically analyzed.

Results

The CIS ratio was higher in DLB than in AD (p < 0.001). The degree of MTL atrophy was lower in DLB than in AD (p < 0.001). The CIS ratio and the degree of MTL atrophy were inversely correlated with DLB (p < 0.001) and with AD (p < 0.05). The CIS ratio did not significantly correlate with DAT density in DLB or with MMSE, FAB, fluctuation score and parkinsonism score. However, the CIS ratio significantly correlated with RAVLT and hallucination scores (both, p < 0.05).

Conclusions

The CIS on FDG-PET in DLB was associated with MTL atrophy but not with striatal DAT density, suggesting that the CIS is a useful neuroimaging biomarker to evaluate coexisting AD-type NFT pathology in vivo. The CIS was also associated with memory impairment and visual hallucination in DLB.

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References

  1. McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, et al. Diagnosis andmanagement of dementia with Lewy bodies:third report of the DLB Consortium. Neurology. 2005;65:1863–72.

    Article  CAS  PubMed  Google Scholar 

  2. Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69:2197–204.

    Article  PubMed  Google Scholar 

  3. Gomez-Tortosa E, Newell K, Irizarry MC, Albert M, Growdon JH, Hyman BT. Clinical and quantitative pathologic correlates of dementia with Lewy bodies. Neurology. 1999;53:1284–91.

    Article  CAS  PubMed  Google Scholar 

  4. Merdes AR, Hansen LA, Jeste DV, Galasko D, Hofstetter CR, Ho GJ, et al. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology. 2003;60(10):1586–90.

    Article  CAS  PubMed  Google Scholar 

  5. Albin RL, Minoshima S, D’Amato CJ, Frey KA, Kuhl DA, Sima AA. Fluoro-deoxyglucose positron emission tomography in diffuse Lewy body disease. Neurology. 1996;47(2):462–6.

    Article  CAS  PubMed  Google Scholar 

  6. Imamura T, Ishii K, Sasaki M, Kitagaki H, Yamaji S, Hirono N, et al. Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer’s disease: a comparative study using positron emission tomography. Neurosci Lett. 1997;235(1–2):49–52.

    Article  CAS  PubMed  Google Scholar 

  7. Ishii K, Imamura T, Sasaki M, Yamaji S, Sakamoto S, Kitagaki H, et al. Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer’s disease. Neurology. 1998;51(1):125–30.

    Article  CAS  PubMed  Google Scholar 

  8. Minoshima S, Foster NL, Sima AA, Frey KA, Albin RL, Kuhl DE. Alzheimer’s disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol. 2001;50(3):358–65.

    Article  CAS  PubMed  Google Scholar 

  9. Shimada H, Hirano S, Shinotoh H, Aotsuka A, Sato K, Tanaka N, et al. Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. Neurology. 2009;73(4):273–8.

    Article  CAS  PubMed  Google Scholar 

  10. Perry EK, Haroutunian V, Davis KL, Levy R, Lantos P, Eagger S, et al. Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer’s disease. Neuroreport. 1994;5(7):747–9.

    Article  CAS  PubMed  Google Scholar 

  11. Higuchi M, Tashiro M, Arai H, Okamura N, Hara S, Higuchi S, et al. Glucose hypometabolism and neuropathological correlates in brains of dementia with Lewy bodies. Exp Neurol. 2000;162(2):247–56.

    Article  CAS  PubMed  Google Scholar 

  12. Mukaetova-Ladinska EB, Andras A, Milne J, Abdel-All Z, Borr I, Jaros E, et al. Synaptic proteins and choline acetyltransferase loss in visual cortexin dementia with Lewy bodies. J Neuropathol Exp Neurol. 2013;72(1):53–60.

    Article  CAS  PubMed  Google Scholar 

  13. Kantarci K, Avula R, Senjem ML, Samikoglu AR, Zhang B, Weigand SD, et al. Dementia with Lewy bodies and Alzheimer disease: neurodegenerative patterns characterized by DTI. Neurology. 2010;74(22):1814–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain. 2002;125(2):391–403.

    Article  CAS  PubMed  Google Scholar 

  15. Klein JC, Eggers C, Kalbe E, Weisenbach S, Hohmann C, Vollmar S, et al. Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo. Neurology. 2010;74(11):885–92.

    Article  CAS  PubMed  Google Scholar 

  16. 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;15:503–10.

    Article  CAS  PubMed  Google Scholar 

  17. Booij J, Speelman JD, Horstink MW, Wolters EC. The clinical benefit of imaging striatal dopamine transporters with [123I]FPCIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. Eur J Nucl Med. 2001;28:266–72.

    Article  CAS  PubMed  Google Scholar 

  18. Shimizu S, Hirao K, Kanetaka H, Namioka N, Hatanaka H, Hirose D, et al. Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2016;43(1):184–92.

    Article  CAS  PubMed  Google Scholar 

  19. Braak H, Ghebremedhin E, Rüb U, Bratzke H, Del Tredici K. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res. 2004;318(1):121–34.

    Article  PubMed  Google Scholar 

  20. Jellinger KA. A critical evaluation of current staging of alpha-synuclein pathology in Lewy body disorders. Biochim Biophys Acta. 2009;1792(7):730–40.

    Article  CAS  PubMed  Google Scholar 

  21. Colloby SJ, McParland S, O’Brien JT, Attems J. Neuropathological correlates of dopaminergic imaging in Alzheimer’s disease and Lewy body dementias. Brain. 2012;135(9):2798–808.

    Article  PubMed  Google Scholar 

  22. Lim SM, Katsifis A, Villemagne VL, Best R, Jones G, Saling M, et al. The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies. J Nucl Med. 2009;50(10):1638–45.

    Article  CAS  PubMed  Google Scholar 

  23. Graff-Radford J, Murray ME, Lowe VJ, Boeve BF, Ferman TJ, Przybelski SA, et al. Dementia with Lewy bodies: basis of cingulate island sign. Neurology. 2014;83(9):801–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Matsuda H, Mizumura S, Nemoto K, Yamashita F, Imabayashi E, Sato N, et al. Automatic voxel-based morphometry of structural MRI by SPM8 plus diffeomorphic anatomic registration through exponentiated lie algebra improves the diagnosis of probable Alzheimer Disease. Am J Neuroradiol. 2012;33(6):1109–14.

    Article  CAS  PubMed  Google Scholar 

  25. Burton EJ, Barber R, Mukaetova-Ladinska EB, Robson J, Perry RH, Jaros E, et al. Medial temporal lobe atrophy on MRI differentiates Alzheimer’s disease from dementia with Lewy bodies and vascular cognitive impairment: a prospective study with pathological verification of diagnosis. Brain. 2009;132(1):195–203.

    Article  CAS  PubMed  Google Scholar 

  26. Kantarci K, Ferman TJ, Boeve BF, Weigand SD, Przybelski S, Vemuri P, et al. Focal atrophy on MRI and neuropathologic classification of dementia with Lewy bodies. Neurology. 2012;79(6):553–60.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Murray ME, Ferman TJ, Boeve BF, Przybelski SA, Lesnick TG, Liesinger AM, et al. MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies. Neurology. 2013;81(19):1681–9.

    Article  PubMed  PubMed Central  Google Scholar 

  28. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–44.

    Article  CAS  PubMed  Google Scholar 

  29. Walker MP, Ayre GA, Cummings JL, Wesnes K, McKeith IG, O’Brien JT, Ballard CG, et al. The clinician assessment of fluctuation and the 1 day fluctuation assessment scale. Two methods to assess fluctuating confusion in dementia. Br J Psychiatry. 2000;177:252–6.

    Article  CAS  PubMed  Google Scholar 

  30. Takeuchi R, Yonekura Y, Matsuda H, Konishi J. Usefulness of a three dimensional stereotaxic ROI template on anatomically standardized 99mTc-ECD SPET. Eur J Nucl Med Mol Imaging. 2002;29:331–41.

    Article  CAS  PubMed  Google Scholar 

  31. 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(12):1491–9.

    Article  PubMed  Google Scholar 

  32. Hayashi H, Kawakatsu S, Suzuki A, Shibuya Y, Kobayashi R, Sato C, Otani K. Application of the VSRAD, a specific and sensitive voxel-based morphometry, to comparison of entorhinal cortex atrophy between dementia with Lewy bodies and Alzheimer’s disease. Dement Geriatr Cogn Disord. 2012;34(5–6):328–31.

    Article  PubMed  Google Scholar 

  33. Nelson PT, Kryscio RJ, Jicha GA, Abner EL, Schmitt FA, Xu LO, et al. Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies. Neurology. 2009;73(14):1127–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mori E, Ikeda M, Kosaka K, Donepezil-DLB Study Investigators. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol. 2012;72(1):41–52.

    Article  CAS  PubMed  Google Scholar 

  35. Graff-Radford J, Boeve BF, Pedraza O, Ferman TJ, Przybelski S, Lesnick TG, et al. Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies. Brain. 2012;135(8):2470–7.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Meguro K, Blaizot X, Kondoh Y, Le Mestric C, Baron JC, Chavoix C. Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET. Implications for Alzheimer’s disease. Brain. 1999;122(8):1519–31.

    Article  PubMed  Google Scholar 

  37. Firbank MJ, Blamire AM, Krishnan MS, Teodorczuk A, English P, Gholkar A, et al. Atrophy is associated with posterior cingulate white matter disruption in dementia with Lewy bodies and Alzheimer’s disease. Neuroimage. 2007;36(1):1–7.

    Article  PubMed  Google Scholar 

  38. Seibyl JP, Marek K, Sheff K, Zoghbi S, Baldwin RM, Charney DS, et al. Iodine-123-beta-CIT and iodine-123-FPCIT SPECT measurement of dopamine transporters in healthy subjects and Parkinson’s patients. J Nucl Med. 1998;39(9):1500–8.

    CAS  PubMed  Google Scholar 

  39. Walker Z, Costa DC, Walker RW, Lee L, Livingston G, Jaros E, et al. Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison. Neurology. 2004;62(9):1568–72.

    Article  CAS  PubMed  Google Scholar 

  40. Walker Z, Costa DC, Walker RW, Shaw K, Gacinovic S, Stevens T, et al. Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry. 2002;73:134–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. McKeith I, O’Brien J, Walker Z, Tatsch K, Booij J, Darcourt J, et al. Sensitivity and specificity of dopamine transporter imaging with123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 2007;6:305–13.

    Article  PubMed  Google Scholar 

  42. O’Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn D, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol. 2004;61:919–25.

    Article  PubMed  Google Scholar 

  43. Sutherland RJ, Whishaw IQ, Kolb B. Contributions of cingulate cortex to two forms of spatial learning and memory. J Neurosci. 1988;8(8):1863–72.

    CAS  PubMed  Google Scholar 

  44. Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol. 1997;42(1):85–94.

    Article  CAS  PubMed  Google Scholar 

  45. Zimny A, Bladowska J, Macioszek A, Szewczyk P, Trypka E, Wojtynska R, et al. Evaluation of the posterior cingulate region with FDG-PET and advanced MR techniques in patients with amnestic mild cognitive impairment: comparison of the methods. J Alzheimers Dis. 2015;44(1):329–38.

    CAS  PubMed  Google Scholar 

  46. Wang L, Laviolette P, O’Keefe K, Putcha D, Pihlajamäki M, Dickerson BC, et al. Intrinsic connectivity between the hippocampus and posteromedial cortex predicts memory performance in cognitively intact older individuals. Neuroimage. 2010;51(2):910–7.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Firbank MJ, Lloyd J, O’Brien JT. The relationship between hallucinations and FDG-PET in dementia with Lewy bodies. Brain Imaging Behav. 2015. doi:10.1007/s11682-015-9434-0.

    PubMed  Google Scholar 

  48. Imamura T, Ishii K, Hirono N, Hashimoto M, Tanimukai S, Kazuai H, et al. Visual hallucinations and regional cerebral metabolism in dementia with Lewy bodies (DLB). Neuroreport. 1999;10(9):1903–7.

    Article  CAS  PubMed  Google Scholar 

  49. Ziebell M, Andersen BB, Pinborg LH, Knudsen GM, Stokholm J, Thomsen G, et al. Striatal dopamine transporter binding does not correlate with clinical severity in dementia with Lewy bodies. J Nucl Med. 2013;54(7):1072–6.

    Article  PubMed  Google Scholar 

  50. Fujishiro H, Ferman TJ, Boeve BF, Smith GE, Graff-Radford NR, Uitti RJ, et al. Validation of the neuropathologic criteria of the third consortium for dementia with Lewy bodies for prospectively diagnosed cases. J Neuropathol Exp Neurol. 2008;67(7):649–56.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors thank the technical staff at the Department of Nuclear Medicine at Fukujuji Hospital, especially Makoto Fukasawa and Hiroya Inoue for invaluable technical assistance.

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Authors and Affiliations

  1. Department of Neurology, Fukujuji Hospital, Japan Anti-Tuberculosis Association, 24-1-3, Matsuyama, Kiyose, Tokyo, 204-8522, Japan

    Tomomichi Iizuka

  2. Division of Nuclear Medicine, Department of Radiology School of Medicine, Keio University, Tokyo, Japan

    Masashi Kameyama

  3. Division of Nuclear Medicine, National Center for Global Health and Medicine, Tokyo, Japan

    Masashi Kameyama

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  1. Tomomichi Iizuka
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Correspondence to Tomomichi Iizuka.

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Iizuka, T., Kameyama, M. Cingulate island sign on FDG-PET is associated with medial temporal lobe atrophy in dementia with Lewy bodies. Ann Nucl Med 30, 421–429 (2016). https://doi.org/10.1007/s12149-016-1076-9

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  • DOI: https://doi.org/10.1007/s12149-016-1076-9

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