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Diagnostic manifestations of total hemispheric glucose metabolism ratio in neuronal network diaschisis: diagnostic implications in Alzheimer’s disease and mild cognitive impairment

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer’s disease (AD) and mild cognitive impairment (MCI).

Methods

We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50–78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014. Ten neurologically healthy individuals (HIs) (mean age 62.5 years, range 43–75, 5 females) served as controls. A neuroimaging expert provided visual assessment of diaschisis. The total hemispheric glucose metabolism ratio (THGr) was calculated, and with area-under the curve of receiver operating characteristics (AUC-ROC) we generated a “Network Diaschisis Test (NDT)”.

Results

The qualitative detection of cerebral (Ce) and cerebellar (Cb) diaschisis was 7/15 (47%), 0/8 (0%), and 0/10 (0%) in AD, MCI, and HI groups, respectively. Median cerebral THGr was 0.68 (range 0.43–0.99), 0.86 (range 0.64–0.98), and 0.95 (range 0.65–1.00) for AD, MCI, and HI groups, respectively (p = 0.04). Median cerebellar THGr was, respectively, 0.70 (range 0.18–0.98), 0.70 (range 0.48–0.81), and 0.84 (range 0.75–0.96) (p = 0.0138). A positive NDT yielded a positive predictive value of 100% for the presence of AD or MCI and a 86% negative predictive value for healthy brain. Moreover, the diagnostic manifestation of THGr between MCI and AD led to a positive predictive value of 100% for AD, but a negative predictive value of 42.9% for MCI.

Conclusion

Patients with AD or MCI had more pronounced diaschisis, lateralized hemispheric glucose metabolism and lower THGr compared to healthy controls. The NDT distinguished AD and MCI patients from HIs, and AD from MCI patients with a high positive predictive value and moderate and low negative predictive values. THGr can be a straightforward source of investigating neuronal network diaschisis in AD and MCI and in other cerebral diseases, across institutions.

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References

  1. von Monakow C. Die Localization im Grosshirn und der Abbau der Funktion durch korticale Herde, Wiesbaden. Germany: JF Bergmann; 1914.

    Google Scholar 

  2. Kang KM, Sohn CH, Choi SH, Jung KH, Yoo RE, Yun TJ, et al. Detection of crossed cerebellar diaschisis in hyperacute ischemic stroke using arterial spin-labeled MR imaging. PLoS One. 2017;12:e0173971. https://doi.org/10.1371/journal.pone.0173971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Abe O, Okubo T, Hayashi N, Saito N, Iriguchi N, Shirouzu I, et al. Temporal changes of the apparent diffusion coefficients of water and metabolites in rats with hemispheric infarction: experimental study of transhemispheric diaschisis in the contralateral hemisphere at 7 tesla. J Cerebr Blood F Met. 2000;20:726–35. https://doi.org/10.1097/00004647-200004000-00010.

    Article  CAS  Google Scholar 

  4. Patronas NJ, Di Chiro G, Smith BH, De La Paz R, Brooks RA, Milam HL, et al. Depressed cerebellar glucose metabolism in supratentorial tumors. Brain Res. 1984;291:93–101.

    Article  CAS  PubMed  Google Scholar 

  5. DeLaPaz RL, Patronas NJ, Brooks RA, Smith BH, Kornblith PL, Milam H, et al. Positron emission tomographic study of suppression of gray-matter glucose utilization by brain tumors. Am J Neuroradiol. 1983;4:826–9.

    CAS  PubMed  Google Scholar 

  6. Alavi A, Mirot A, Newberg A, Alves W, Gosfield T, Berlin J, et al. Fluorine-18-FDG evaluation of crossed cerebellar diaschisis in head injury. J Nucl Med. 1997;38:1717–20.

    CAS  PubMed  Google Scholar 

  7. Akiyama H, Harrop R, McGeer PL, Peppard R, McGeer EG. Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease. Neurology. 1989;39:541–8.

    Article  CAS  PubMed  Google Scholar 

  8. Scholl M, Damian A, Engler H. Fluorodeoxyglucose PET in neurology and psychiatry. PET Clin. 2014;9:371–90, v. https://doi.org/10.1016/j.cpet.2014.07.005.

    Article  PubMed  Google Scholar 

  9. Sporns O, Tononi G, Kotter R. The human connectome: a structural description of the human brain. PLoS Comput Biol. 2005;1:e42. https://doi.org/10.1371/journal.pcbi.0010042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Glasser MF, Coalson TS, Robinson EC, Hacker CD, Harwell J, Yacoub E, et al. A multi-modal parcellation of human cerebral cortex. Nature. 2016;536:171–8. https://doi.org/10.1038/nature18933.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Savio A, Funger S, Tahmasian M, Rachakonda S, Manoliu A, Sorg C, et al. Resting state networks as simultaneously measured with fMRI and PET. J Nucl Med. 2017. https://doi.org/10.2967/jnumed.116.185835.

  12. Magistretti PJ. Neuron-glia metabolic coupling and plasticity. J Exp Biol. 2006;209:2304–11. https://doi.org/10.1242/jeb.02208.

    Article  CAS  PubMed  Google Scholar 

  13. Delbeuck X, Van der Linden M, Collette F. Alzheimer's disease as a disconnection syndrome? Neuropsychol Rev. 2003;13:79–92.

    Article  CAS  PubMed  Google Scholar 

  14. Delbeuck X, Collette F, Van der Linden MI. Alzheimer’s disease a disconnection syndrome? Evidence from a crossmodal audio-visual illusory experiment. Neuropsychologia. 2007;45:3315–23.

    Article  CAS  PubMed  Google Scholar 

  15. Segtnan EA, Gjedde A, Høilund-Carlsen PF. A new PET method for quantification of total hemispheric glycolysis and diaschisis: A case report in a patient with stroke 13 years ago. 10th FENS Forum of Neuroscience; Copenhagen 2016.

  16. Segtnan EA, Grupe P, Jarden JO, Gerke O, Ivanidze J, Christlieb SB, et al. Prognostic implications of total hemispheric glucose metabolism ratio in cerebro-cerebellar diaschisis. J Nucl Med. 2017;58:768–73. https://doi.org/10.2967/jnumed.116.180398.

    Article  CAS  PubMed  Google Scholar 

  17. Baron JC, Levasseur M, Mazoyer B, Legault-Demare F, Mauguiere F, Pappata S, et al. Thalamocortical diaschisis: positron emission tomography in humans. J Neurol Neurosur Ps. 1992;55:935–42.

    Article  CAS  Google Scholar 

  18. Lolk A, Nielsen H, Andersen K, Andersen J, Kragh-Sorensen P. CAMCOG as a screening instrument for dementia: the Odense study. Cambridge cognitive examination. Acta Psychiatr Scand. 2000;102:331–5.

    Article  CAS  PubMed  Google Scholar 

  19. Coffin M, Sukhatme S. Receiver operating characteristic studies and measurement errors. Biometrics. 1997:823–37.

  20. Drzezga A, Lautenschlager N, Siebner H, Riemenschneider M, Willoch F, Minoshima S, et al. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur J Nucl Med Mol Imaging. 2003;30:1104–13. https://doi.org/10.1007/s00259-003-1194-1.

    Article  PubMed  Google Scholar 

  21. Fouquet M, Desgranges B, Landeau B, Duchesnay E, Mezenge F, de la Sayette V, et al. Longitudinal brain metabolic changes from amnestic mild cognitive impairment to Alzheimer’s disease. Brain. 2009;132:2058–67. https://doi.org/10.1093/brain/awp132.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA. 2003;100:253–8. https://doi.org/10.1073/pnas.0135058100.

    Article  CAS  PubMed  Google Scholar 

  23. Weise CM, Chen K, Chen Y, Kuang X, Savage CR, Reiman EM. Left lateralized cerebral glucose metabolism declines in amyloid-beta positive persons with mild cognitive impairment. Neuroimage Clin. 2018;20:286–96. https://doi.org/10.1016/j.nicl.2018.07.016.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mesulam MM, Weintraub S, Rogalski EJ, Wieneke C, Geula C, Bigio EH. Asymmetry and heterogeneity of Alzheimer's and frontotemporal pathology in primary progressive aphasia. Brain. 2014;137:1176–92. https://doi.org/10.1093/brain/awu024.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Musiek ES, Saboury B, Mishra S, Chen Y, Reddin JS, Newberg AB, et al. Feasibility of estimation of brain volume and 2-deoxy-2-(18)F-fluoro-D-glucose metabolism using a novel automated image analysis method: application in Alzheimer's disease. Hellenic J Nucl Med. 2012;15:190–6. https://doi.org/10.1967/s002449910052.

    Article  Google Scholar 

  26. Alavi A, Newberg AB, Souder E, Berlin JA. Quantitative analysis of PET and MRI data in normal aging and Alzheimer's disease: atrophy weighted total brain metabolism and absolute whole brain metabolism as reliable discriminators. J Nucl Med: Off Publ, Soc Nucl Med. 1993;34:1681–7.

    CAS  Google Scholar 

  27. Mosconi L, Brys M, Switalski R, Mistur R, Glodzik L, Pirraglia E, et al. Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism. Proc Natl Acad Sci USA. 2007;104:19067–72. https://doi.org/10.1073/pnas.0705036104.

    Article  PubMed  Google Scholar 

  28. Rodell AB, O'Keefe G, Rowe CC, Villemagne VL, Gjedde A. Cerebral blood flow and Abeta-amyloid estimates by WARM analysis of [11C]PiB uptake distinguish among and between neurodegenerative disorders and aging. Front Aging Neurosci. 2016;8:321. https://doi.org/10.3389/fnagi.2016.00321.

    Article  CAS  PubMed  Google Scholar 

  29. Kern W, Buchner T, Wormann B, Ritter J, Creutzig U, Hiddemann W. Akute Leukämien Prognostische Faktoren und Therapiestrategien. Internist. 1999;40:983–6. https://doi.org/10.1007/s001080050427.

    Article  CAS  PubMed  Google Scholar 

  30. Guo CC, Tan R, Hodges JR, Hu X, Sami S, Hornberger M. Network-selective vulnerability of the human cerebellum to Alzheimer's disease and frontotemporal dementia. Brain. 2016;139:1527–38. https://doi.org/10.1093/brain/aww003.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Catafau AM, Bullich S, Seibyl JP, Barthel H, Ghetti B, Leverenz J, et al. Cerebellar amyloid-beta plaques: how frequent are they, and do they influence 18F-Florbetaben SUV ratios? J Nucl Med: Off Publ, Soc Nucl Med. 2016;57:1740–5. https://doi.org/10.2967/jnumed.115.171652.

    Article  CAS  Google Scholar 

  32. Lyoo CH, Ikawa M, Liow JS, Zoghbi SS, Morse CL, Pike VW, et al. Cerebellum can serve as a pseudo-reference region in Alzheimer disease to detect neuroinflammation measured with PET radioligand binding to translocator protein. J Nucl Med: Off Publ, Soc Nucl Med. 2015;56:701–6. https://doi.org/10.2967/jnumed.114.146027.

  33. Irwin RJ, Irwin TC. A principled approach to setting optimal diagnostic thresholds: where ROC and indifference curves meet. Eur J Intern Med. 2011;22:230–4. https://doi.org/10.1016/j.ejim.2010.12.012.

    Article  PubMed  Google Scholar 

  34. Altman DG. ROC curves and confidence intervals: getting them right. Heart. 2000;83:236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chirles TJ, Reiter K, Weiss LR, Alfini AJ, Nielson KA, Smith JC. Exercise training and functional connectivity changes in mild cognitive impairment and healthy elders. J Alzheimers Dis. 2017;57:845–56. https://doi.org/10.3233/JAD-161151.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Heyn P, Abreu BC, Ottenbacher KJ. The effects of exercise training on elderly persons with cognitive impairment and dementia: a meta-analysis1. Arch Phys Med Rehabil. 2004;85:1694–704.

    Article  PubMed  Google Scholar 

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Acknowledgments

Asbjoern Hrobjartsson, Casper Strandholdt and Andreas Andersen are acknowledged for fruitful discussions of creating an exploratory diagnostic test and pathological aspects of dementia. Sofie Bæk Christlieb is acknowledged for help with the manuscript.

Funding

This article was not funded by any grants.

Author information

Author notes

  1. Albert Gjedde and Poul Flemming Høilund-Carlsen contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark

    Eivind A. Segtnan, Caius Constantinescu, Peter Grupe, Oke Gerke, Jorun Holm, Malene G. Hildebrandt, Albert Gjedde & Poul Flemming Høilund-Carlsen

  2. Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

    Eivind A. Segtnan, Caius Constantinescu, Heini í Dali, Olaf Emil Strøm, Lene Wermuth, Malene G. Hildebrandt, Albert Gjedde & Poul Flemming Høilund-Carlsen

  3. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Alireza Majdi, Saeed Sadigh-Eteghad & Albert Gjedde

  4. Division of Nuclear Medicine, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Abass Alavi

  5. Dementia Clinic, Department of Neurology, Odense University Hospital, Odense C, Denmark

    Lene Wermuth

  6. Department of Neuroscience, Panum Institute, University of Copenhagen, Copenhagen, Denmark

    Albert Gjedde

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  1. Eivind A. Segtnan
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Correspondence to Poul Flemming Høilund-Carlsen.

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Segtnan, E.A., Majdi, A., Constantinescu, C. et al. Diagnostic manifestations of total hemispheric glucose metabolism ratio in neuronal network diaschisis: diagnostic implications in Alzheimer’s disease and mild cognitive impairment. Eur J Nucl Med Mol Imaging 46, 1164–1174 (2019). https://doi.org/10.1007/s00259-018-4248-0

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