Voxel-wise analysis of 18F-fluorodeoxyglucose metabolism in correlation with variations in the presentation of Alzheimer’s disease: a clinician’s guide
BACKGROUND Diagnostic imaging can be applied in the management of Alzheimer’s disease as it provides structural and functional information to exclude possible secondary causes and offers additional information, especially in atypical cases of Alzheimer’s disease. The utility of positron emission tomography/computed tomography (PET/CT) can help in the noninvasive diagnosis of Alzheimer’s disease by voxel-wise quantification of cerebral 18F-fluorodeoxyglucose (FDG) metabolism.
METHODS This prospective study was conducted among 10 subjects with Alzheimer’s disease and 10 healthy control subjects who underwent neuropsychological testing and 18F-FDG PET/CT scans. Images of the brain were postprocessed using voxel-wise analysis and segmented into 20 regions of interest. The standardized uptake value (SUV)max/SUVmean/standard deviation of SUVmean results were analyzed accordingly and correlated with the subjects’ Montreal cognitive assessment (MoCA) results that were adjusted for age and education level.
RESULTS Hypometabolism at the right parietal lobe significantly correlated with increasing age and lower MoCA scores. Global hypometabolism was observed in subjects who had advanced Alzheimer’s disease but preserved primary somatosensory cortices (S1) region metabolism. Predominance of frontal lobe hypometabolism was a feature of subjects with Alzheimer’s disease having associated depressive symptoms.
CONCLUSIONS 18F-FDG PET/CT voxel-wise analysis can be used for quantitative assessment and can assist clinicians in the diagnosis of Alzheimer’s disease and other variations of the disease spectrum.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Washington, D.C: American Psychiatric Association; 2013. https://doi.org/10.1176/appi.books.9780890425596
Rizzi L, Rosset I, Roriz-Cruz M. Global epidemiology of dementia: Alzheimer's and vascular types. BioMed Res Int. 2014;2014:908915. https://doi.org/10.1155/2014/908915
Lestari S, Mistivani I, Rumende CM, Kusumaningsih W. Comparison between mini mental state examination (MMSE) and Montreal cognitive assessment Indonesian version (MoCAIna) as an early detection of cognitive impairments in poststroke patients. J Phys Conf Ser. 2017;884:012153. https://doi.org/10.1088/1742-6596/884/1/012153
Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695−9. https://doi.org/10.1111/j.1532-5415.2005.53221.x
Martin Prince, Adelina Comas-Herrera, Martin Knapp, Maëlenn Guerchet, Karagiannidou M. World Alzheimer Report 2016: Improving healthcare for people living with dementia (Coverage, Quality and costs now and in the future). London: Alzheimer's Disease International, 2016.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, 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(3):263−9. https://doi.org/10.1016/j.jalz.2011.03.005
Berti V, Osorio RS, Mosconi L, Li Y, De Santi S, de Leon MJ. Early detection of Alzheimer's disease with PET imaging. Neurodegener Dis. 2010;7(1−3):131−5. https://doi.org/10.1159/000289222
Suppiah S, Ahmad Saad FF, Mohad Azmi NH, Nordin AJ. Mapping 18F-fluorodeoxyglucose metabolism using PET/CT for the assessment of treatment response in non-small cell lung cancer patients undergoing epidermal growth factor receptor inhibitor treatment: a single-centre experience. Mal J Med Health Sci. 2017;13(1):9−15.
Berti V, Mosconi L, Pupi A. Brain: normal variations and benign findings in FDG-PET/CT imaging. PET Clin. 2014;9(2):129−40. https://doi.org/10.1016/j.cpet.2013.10.006
Suppiah S, Ching SM, Nordin AJ, Vinjamuri S. The role of PET/CT amyloid imaging compared with Tc99m-HMPAO SPECT imaging for diagnosing Alzheimer's disease. Medical J Malaysia. 2018;73(3):141−6.
Suppiah S, Chang WL, Hassan HA, Kaewput C, Asri AA, Saad FF, et al. Systematic review on the accuracy of positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging in the management of ovarian cancer: is functional information really needed? World J Nucl Med. 2017;16(3):176−85. https://doi.org/10.4103/wjnm.WJNM_31_17
Suppiah S, Zakaria MH, Khalid B, Mohamad Saini S, Othman N. Diagnostic dilemma of reactive arthritis aided by multimodality imaging using MRI, CECT and 18F-FDG PET/CT scans. Mal J Med Health Sci. 2017;13(1):73−7.
Erlandsson K, Buvat I, Pretorius PH, Thomas BA, Hutton BF. A review of partial volume correction techniques for emission tomography and their applications in neurology, cardiology and oncology. Physics Med Biol. 2012;57(21):R119−59. https://doi.org/10.1088/0031-9155/57/21/R119
Smailagic N, Vacante M, Hyde C, Martin S, Ukoumunne O, Sachpekidis C. 18F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2015;1:CD010632. https://doi.org/10.1002/14651858.CD010632.pub2
Minoshima S. Imaging Alzheimer's disease: clinical applications. Neuroimaging Clin N Am. 2003;13(4):769−80. https://doi.org/10.1016/S1052-5149(03)00099-6
Azmi NH, Suppiah S, Liong CW, Noor NM, Md Said S, Hanafi M, et al. Reliability of standardized uptake value normalized to lean body mass using the liver as a reference organ, in contrast-enhanced 18F-FDG PET/CT imaging. Radiat Phys Chem. 2018;147:35−9. https://doi.org/10.1016/j.radphyschem.2018.01.019
Förster S, Grimmer T, Miederer I, Henriksen G, Yousefi BH, Graner P, et al. Regional expansion of hypometabolism in Alzheimer's disease follows amyloid deposition with temporal delay. Biol Psychiatry. 2012;71(9):792−7. https://doi.org/10.1016/j.biopsych.2011.04.023
Weyts K, Vernooij M, Steketee R, Valkema R, Smits M. Qualitative agreement and diagnostic performance of arterial spin labelling MRI and FDG PET-CT in suspected early-stage dementia: comparison of arterial spin labelling MRI and FDG PET-CT in suspected dementia. Clin Imaging. 2017;45:1−7. https://doi.org/10.1016/j.clinimag.2017.05.008
Zhou M, Zhang F, Zhao L, Qian J, Dong C. Entorhinal cortex: a good biomarker of mild cognitive impairment and mild Alzheimer's disease. Rev Neurosci. 2016;27(2):185−95. https://doi.org/10.1515/revneuro-2015-0019
Reiman EM, Alzheimer's Disease Biomarkers Working Group for the Alliance for Aging Research. Fluorodeoxyglucose positron emission tomography: emerging roles in the evaluation of putative Alzheimer's disease-modifying treatments. Neurobiol Aging. 2011;32(Suppl 1):S44−7. https://doi.org/10.1016/j.neurobiolaging.2011.09.007
Abdul Aziz SA, Azmi MH, Nordin AJ, Ahmad Saad FF, Ibrahim N, Wan Adnan WA, et al. Voxel-based morphometric difference in metabolic activity of 50 to 73 years old healthy adult brain: a PET/CT study. Int J Control Theory Appl. 2016;9(31):37−43.
Borland E, Nägga K, Nilsson PM, Minthon L, Nilsson ED, Palmqvist S. The Montreal Cognitive Assessment: normative data from a large Swedish population-based cohort. J Alzheimers Dis. 2017;59(3):893−901. https://doi.org/10.3233/JAD-170203
Shivamurthy VK, Tahari AK, Marcus C, Subramaniam RM. Brain FDG PET and the diagnosis of dementia. AJR AM J Roentgenol. 2015;204(1):W76−85. https://doi.org/10.2214/AJR.13.12363
Tripathi M, Tripathi M, Damle N, Kushwaha S, Jaimini A, D'Souza MM, et al. Differential diagnosis of neurodegenerative dementias using metabolic phenotypes on F-18 FDG PET/CT. Neuroradiol J. 2014;27(1):13−21. https://doi.org/10.15274/NRJ-2014-10002
Suárez-González A, Henley SM, Walton J, Crutch SJ. Posterior cortical atrophy: an atypical variant of Alzheimer disease. Psychiatr Clin North Am. 2015;38(2):211−20. https://doi.org/10.1016/j.psc.2015.01.009
Galton CJ, Patterson K, Xuereb JH, Hodges JR. Atypical and typical presentations of Alzheimer's disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain. 2000;123(3):484−98. https://doi.org/10.1093/brain/123.3.484
Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, et al. Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol. 2008;7(9):812−26. https://doi.org/10.1016/S1474-4422(08)70169-8
Silverman DHS. Brain 18F-FDG PET in the diagnosis of neurodegenerative dementias: comparison with perfusion SPECT and with clinical evaluations lacking nuclear imaging. J Nucl Med. 2004;45(4):594−607.
Yu P, Dean RA, Halla SD, Qi Y, Sethuraman G, Willis BA, et al. Enriching amnestic mild cognitive impairment populations for clinical trials: optimal combination of biomarkers to predict conversion to dementia. J Alzheimers Dis. 2012;32(2):373−85. https://doi.org/10.3233/JAD-2012-120832
Braak H, Braak E. Neuropathological stageing of Alzheimerrelated changes. Acta Neuropathol. 1991;82(4):239−59. https://doi.org/10.1007/BF00308809
Stephen JM, Montaño R, Donahue CH, Adair JC, Knoefel J, Qualls C, et al. Somatosensory responses in normal aging, mild cognitive impairment, and Alzheimer's disease. J Neural Transm. 2010;117(2):217−25. https://doi.org/10.1007/s00702-009-0343-5
Teipel SJ, Stahl R, Dietrich O, Schoenberg SO, Perneczky R, Bokde AL, et al. Multivariate network analysis of fiber tract integrity in Alzheimer's disease. Neuroimage. 2007;34(3):985−95. https://doi.org/10.1016/j.neuroimage.2006.07.047
Victoroff J, Lin FV, Coburn KL, Shillcutt SD, Voon V, Ducharme S. Noncognitive behavioral changes associated with Alzheimer's disease: implications of neuroimaging findings. J Neuropsychiatry Clin Neurosci. 2017;30(1):14−21. https://doi.org/10.1176/appi.neuropsych.16080155
Reitz C. Genetic diagnosis and prognosis of Alzheimer's disease: challenges and opportunities. Expert Rev Mol Diagn. 2015;15(3):339−48. https://doi.org/10.1586/14737159.2015.1002469
Brown RK, Bohnen NI, Wong KK, Minoshima S, Frey KA. Brain PET in suspected dementia: patterns of altered FDG metabolism. Radiographics. 2014;34(3):684−701. https://doi.org/10.1148/rg.343135065
Copyright (c) 2019 Siti Aishah Abdul Aziz, Loh Jia Ling, Fathinul Fikri Ahmad Saad, Abdul Jalil Nordin, Normala Ibrahim, Arlina Nuruddin, Elinda Tunan, Rosalina Rosalina, M. Iqbal Saripan, Subapriya Suppiah
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.