Visually preserved metabolism in posterior cingulate cortex relative to hypometabolism in precuneus and cuneus, the cingulate island sign, is a feature of dementia with Lewy bodies (DLB) on FDG-PET. Lower cingulate island sign ratio (posterior cingulate cortex/cuneus+precuneus; FDG-CISr) values have been associated with a higher Braak neurofibrillary tangle stage in autopsied DLB. Using voxel-wise analysis, we assessed the patterns of regional cortical perfusion and metabolism, and using an atlas-based approach, we measured perfusion cingulate island sign ratio on arterial spin labeling MRI (ASL-CISr), and its associations with FDG-CISr, uptake on tau-PET and clinical severity in DLB. Our study sample (n = 114) included clinically probable DLB patients (n = 19), age-matched patients with probable Alzheimer's disease dementia (AD; n = 19) and matched controls (n = 76) who underwent MRI with 3-dimensional pseudo-continuous arterial spin labeling, 18F-FDG-PET and 18F-AV-1451 tau PET. Patterns of cortical perfusion and metabolism were derived from quantitative maps using Statistical Parametric Mapping. DLB patients showed hypoperfusion on ASL-MRI in precuneus, cuneus and posterior parieto-occipital cortices, compared to controls, and relatively spared posterior cingulate gyrus, similar to pattern of hypometabolism on FDG-PET. DLB patients had higher ASL-CISr and FDG-CISr than AD patients (p <0.001). ASL-CISr correlated with FDG-CISr in DLB patients (r = 0.67; p =0.002). Accuracy of distinguishing DLB from AD patients was 0.80 for ASL-CISr and 0.91 for FDG-CISr. Lower ASL-CISr was moderately associated with a higher composite medial temporal AV-1451 uptake (r = -0.50; p =0.03) in DLB. Lower perfusion in precuneus and cuneus was associated with worse global clinical scores. In summary, the pattern of cortical hypoperfusion on ASL-MRI is similar to hypometabolism on FDG-PET, and respective cingulate island sign ratios correlate with each other in DLB. Non-invasive and radiotracer-free ASL-MRI may be further developed as a tool for the screening and diagnostic evaluation of DLB patients in a variety of clinical settings where FDG-PET is not accessible.

Department of Health Sciences Mayo Clinic Rochester MN United States

Department of Neurology Mayo Clinic Rochester MN United States

Department of Psychiatry and Psychology Mayo Clinic Jacksonville FL United States

Department of Radiology Mayo Clinic Rochester MN United States

Department of Radiology Mayo Clinic Rochester MN United States; Department of Information Technology Mayo Clinic Rochester MN United States

Department of Radiology Mayo Clinic Rochester MN United States; Department of Neurology Charles University 2 Faculty of Medicine Motol University Hospital Prague Czech Republic

Zobrazit více v PubMed

AASM . American Academy of Sleep Medicine; Chicago: 2005. International Classification of Sleep Disorders—2: Diagnostic and Coding Manual.

Alsop D.C., Detre J.A., Golay X., Gunther M., Hendrikse J., Hernandez-Garcia L. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn. Reson. Med. 2015;73(1):102–116. PubMed PMC

Binnewijzend M.A., Kuijer J.P., van der Flier W.M., Benedictus M.R., Moller C.M., Pijnenburg Y.A. Distinct perfusion patterns in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies. Eur. Radiol. 2014;24(9):2326–2333. PubMed

Buxton R.B., Frank L.R. A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation. J. Cereb. Blood Flow Metab. 1997;17(1):64–72. PubMed

Chen Y., Wolk D.A., Reddin J.S., Korczykowski M., Martinez P.M., Musiek E.S. Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease. Neurology. 2011;77(22):1977–1985. PubMed PMC

Dai W., Garcia D., de Bazelaire C., Alsop D.C. Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn. Reson. Med. 2008;60(6):1488–1497. PubMed PMC

Detre J.A., Wang J., Wang Z., Rao H. Arterial spin-labeled perfusion MRI in basic and clinical neuroscience. Curr. Opin. Neurol. 2009;22(4):348–355. PubMed

Ferman T.J., Smith G.E., Boeve B.F., Ivnik R.J., Petersen R.C., Knopman D. DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging. Neurology. 2004;62(2):181–187. PubMed

Graff-Radford J., Boeve B.F., Pedraza O., Ferman T.J., Przybelski S., Lesnick T.G. Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies. Brain. 2012;135(Pt 8):2470–2477. PubMed PMC

Graff-Radford J., Murray M.E., Lowe V.J., Boeve B.F., Ferman T.J., Przybelski S.A. Dementia with Lewy bodies: basis of cingulate island sign. Neurology. 2014;83(9):801–809. PubMed PMC

Halliday G.M., Holton J.L., Revesz T., Dickson D.W. Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol. 2011;122(2):187–204. PubMed

Hammes J., Bischof G.N., Giehl K., Faber J., Drzezga A., Klockgether T. Elevated in vivo [18F]-AV-1451 uptake in a patient with progressive supranuclear palsy. Mov. Disord. 2017;32(1):170–171. PubMed

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. 2016;30(6):421–429. PubMed

Iizuka T., Iizuka R., Kameyama M. Cingulate island sign temporally changes in dementia with Lewy bodies. Sci. Rep. 2017;7(1):14745. PubMed PMC

Imabayashi E., Yokoyama K., Tsukamoto T., Sone D., Sumida K., Kimura Y. The cingulate island sign within early Alzheimer's disease-specific hypoperfusion volumes of interest is useful for differentiating Alzheimer's disease from dementia with Lewy bodies. EJNMMI Res. 2016;6(1):67. PubMed PMC

Imabayashi E., Soma T., Sone D., Tsukamoto T., Kimura Y., Sato N. Validation of the cingulate island sign with optimized ratios for discriminating dementia with Lewy bodies from Alzheimer's disease using brain perfusion SPECT. Ann. Nucl. Med. 2017;31(7):536–543. PubMed PMC

Imamura T., Ishii K., Sasaki M., Kitagaki H., Yamaji S., Hirono N. 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. PubMed

Irwin D.J., Grossman M., Weintraub D., Hurtig H.I., Duda J.E., Xie S.X. Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. Lancet Neurol. 2017;16(1):55–65. PubMed PMC

Ivnik R.J., Malec J.F., Smith G.E., Tangalos E.G., Petersen R.C., Kokmen E. Mayo's Older Americans Normative Studies: WAIS-R, WMS-R and AVLT norms for ages 56 through 97. Clin. Neuropsychol. 1992;6(Suppl. 2):1–104.

Kantarci K., Lowe V.J., Boeve B.F., Weigand S.D., Senjem M.L., Przybelski S.A. Multimodality imaging characteristics of dementia with Lewy bodies. Neurobiol. Aging. 2012;33(9):2091–2105. Sep 21,2012. PubMed PMC

Kantarci K., Lowe V.J., Boeve B.F., Senjem M.L., Tosakulwong N., Lesnick T.G. AV-1451 tau and beta-amyloid positron emission tomography imaging in dementia with Lewy bodies. Ann. Neurol. 2017;81(1):58–67. PubMed PMC

Kokmen E., Smith G.E., Petersen R.C., Tangalos E., Ivnik R.C. The short test of mental status. Correlations with standardized psychometric testing. Arch. Neurol. 1991;48(7):725–728. PubMed

Lim S.M., Katsifis A., Villemagne V.L., Best R., Jones G., Saling M. 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):1638–1645. PubMed

Mckeith I.G., Dickson D.W., Lowe J., Emre M., O'Brien J.T., Feldman H. Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology. 2005;65(12):1863–1872. PubMed

Mckeith I.G., Boeve B.F., Dickson D.W., Halliday G., Taylor J.P., Weintraub D. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB consortium. Neurology. 2017;89(1):88–100. PubMed PMC

Mckhann G.M., Knopman D.S., Chertkow H., Hyman B.T., Jack C.R., Jr., Kawas C.H. 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(3):263–269. PubMed PMC

Meltzer C.C., Kinahan P.E., Greer P.J., Nichols T.E., Comtat C., Cantwell M.N. Comparative evaluation of MR-based partial-volume correction schemes for PET. J. Nucl. Med. 1999;40(12):2053–2065. PubMed

Merdes A.R., Hansen L.A., Jeste D.V., Galasko D., Hofstetter C.R., Ho G.J. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology. 2003;60(10):1586–1590. PubMed

Minoshima S., Giordani B., Berent S., Frey K.A., Foster N.L., Kuhl D.E. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann. Neurol. 1997;42(1):85–94. PubMed

Minoshima S., Foster N.L., Sima A.A., Frey K.A., Albin R.L., Kuhl D.E. Alzheimer's disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann. Neurol. 2001;50(3):358–365. PubMed

Mok W., Chow T.W., Zheng L., Mack W.J., Miller C. Clinicopathological concordance of dementia diagnoses by community versus tertiary care clinicians. Am. J. Alzheimers Dis. Other Dement. 2004;19(3):161–165. PubMed PMC

Musiek E.S., Chen Y., Korczykowski M., Saboury B., Martinez P.M., Reddin J.S. Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer's disease. Alzheimers Dement. 2012;8(1):51–59. PubMed PMC

Nelson P.T., Jicha G.A., Kryscio R.J., Abner E.L., Schmitt F.A., Cooper G. Low sensitivity in clinical diagnoses of dementia with Lewy bodies. J. Neurol. 2010;257(3):359–366. PubMed PMC

Petersen R.C., Roberts R.O., Knopman D.S., Geda Y.E., Cha R.H., Pankratz V.S. Prevalence of mild cognitive impairment is higher in men. The Mayo Clinic study of aging. Neurology. 2010;75(10):889–897. PubMed PMC

Reiman E.M., Caselli R.J., Yun L.S., Chen K., Bandy D., Minoshima S. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N. Engl. J. Med. 1996;334(12):752–758. PubMed

Roberts R.O., Geda Y.E., Knopman D.S., Cha R.H., Pankratz V.S., Boeve B.F. The Mayo Clinic study of aging: design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology. 2008;30(1):58–69. PubMed PMC

Roquet D., Sourty M., Botzung A., Armspach J.P., Blanc F. Brain perfusion in dementia with Lewy bodies and Alzheimer's disease: an arterial spin labeling MRI study on prodromal and mild dementia stages. Alzheimers Res. Ther. 2016;8:29. PubMed PMC

Taylor J.P., Firbank M.J., He J., Barnett N., Pearce S., Livingstone A. Visual cortex in dementia with Lewy bodies: magnetic resonance imaging study. Br. J. Psychiatry. 2012;200(6):491–498. PubMed PMC

Tzourio-Mazoyer N., Landeau B., Papathanassiou D., Crivello F., Etard O., Delcroix N. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage. 2002;15(1):273–289. PubMed

Whitwell J.L., Graff-Radford J., Singh T.D., Drubach D.A., Senjem M.L., Spychalla A.J. 18F-FDG PET in posterior cortical atrophy and dementia with Lewy bodies. J. Nucl. Med. 2017;58(4):632–638. PubMed PMC

Williams D.S., Detre J.A., Leigh J.S., Koretsky A.P. Magnetic resonance imaging of perfusion using spin inversion of arterial water. Proc. Natl. Acad. Sci. U. S. A. 1992;89(1):212–216. PubMed PMC

Wolk D.A., Detre J.A. Arterial spin labeling MRI: an emerging biomarker for Alzheimer's disease and other neurodegenerative conditions. Curr. Opin. Neurol. 2012;25(4):421–428. PubMed PMC

Xu G., Rowley H.A., Wu G., Alsop D.C., Shankaranarayanan A., Dowling M. Reliability and precision of pseudo-continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with 15O-water PET in elderly subjects at risk for Alzheimer's disease. NMR Biomed. 2010;23(3):286–293. PubMed PMC

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies