Early diagnosis of Alzheimer’s disease: potential of ¹⁸F-FDG PET as a biomarker of neurodegeneration

Abstract

BACKGROUND: Dementia is considered one of the most actual medical problems of our time, being one of the main causes of disability among the elderly, and its prevalence will only increase in the coming years. The first place among conditions leading to dementia is given to Alzheimer’s disease (up to 70%). The effectiveness of Alzheimer’s disease therapy largely depends on the timeliness of diagnosis, which leads to the need to search for diagnostic markers that allow to detect the disease at the earliest stages.

AIM: To evaluate the possibilities of using ¹⁸F-FDG PET for the early diagnosis of Alzheimer’s disease.

MATERIALS AND METHODS: Cerebral metabolism was assessed using positron emission tomography with ¹⁸F-FDG. A total of 183 patients were divided into groups depending on their diagnosis and the severity of cognitive impairment.

RESULTS: A characteristic pattern of cerebral metabolic disorders has been established in patients with Alzheimer’s disease. It can be detected in the early pre-dementia stages and has developmental features as the disease progresses. The pattern was characterized by bilateral hypometabolism in the parietal and temporal cortex with a predominance in its mediobasal sections. An important marker of the development of the neurodegenerative process was a metabolic disorder of the cingulate gyrus, the posterior sections of which are affected already at the earliest stages of the disease, while the involvement of its anterior sections reflects the transition to the stage of severe dementia. Described metabolic disorders prevailed in the dominant (left) brain hemisphere at all stages of the disease.

CONCLUSION: Currently ¹⁸F-FDG PET can be considered the most informative of the available methods for the early diagnosis of Alzheimer’s disease which have a fairly high degree of accuracy.

Keywords

Alzheimer’s disease / cerebral metabolism / cognitive disorders / dementia / neuroimaging / positron emission tomography / mild cognitive impairment

References

[1] Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7(1):33. doi: 10.1038/s41572-021-00269-y

[2] Knopman D.S., Amieva H., Petersen R.C., et al. Alzheimer disease // Nat. Rev. Dis. Primers. 2021. Vol. 7, N 1. P. 33. doi: 10.1038/s41572-021-00269-y

[3] Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7(1):33. doi: 10.1038/s41572-021-00269-y

[4] Alzheimer’s Disease facts and figures. Alzheimers Dement. 2021;17(3):327–406. doi: 10.1002/alz.12328

[5] Alzheimer’s Disease facts and figures // Alzheimers Dement. 2021. Vol. 17, N 3. P. 327–406. doi: 10.1002/alz.12328

[6] Alzheimer’s Disease facts and figures. Alzheimers Dement. 2021;17(3):327–406. doi: 10.1002/alz.12328

[7] Emelin AYu, Lobzin VYu, Vorobyov SV. Cognitive impairment: a guide for physicians. Moscow; 2019. 414 p. (In Russ.) ISBN 978-5-00030-673-4

[8] Емелин А.Ю., Лобзин В.Ю., Воробьев С.В. Когнитивные нарушения: руководство для врачей. М., 2019. 414 с. ISBN 978-5-00030-673-4

[9] Emelin AYu, Lobzin VYu, Vorobyov SV. Cognitive impairment: a guide for physicians. Moscow; 2019. 414 p. (In Russ.) ISBN 978-5-00030-673-4

[10] McKhann G, Drachman D, Folstein M, et al. 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):939–944. doi: 10.1212/wnl.34.7.939

[11] McKhann G., Drachman D., Folstein M., et al. 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. Vol. 34, N 7. P. 939–944. doi: 10.1212/wnl.34.7.939

[12] McKhann G, Drachman D, Folstein M, et al. 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):939–944. doi: 10.1212/wnl.34.7.939

[13] Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment 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):270–279. doi: 10.1016/j.jalz.2011.03.008

[14] Albert M.S., DeKosky S.T., Dickson D., et al. The diagnosis of mild cognitive impairment 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. Vol. 7, N 3. P. 270–279. doi: 10.1016/j.jalz.2011.03.008

[15] Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment 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):270–279. doi: 10.1016/j.jalz.2011.03.008

[16] Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–562. doi: 10.1016/j.jalz.2018.02.018

[17] Jack C.R. Jr., Bennett D.A., Blennow K., et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease // Alzheimers Dement. 2018. Vol. 14, N 4. P. 535–562. doi: 10.1016/j.jalz.2018.02.018

[18] Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–562. doi: 10.1016/j.jalz.2018.02.018

[19] Dubois B, Villain N, Frisoni GB, et al. Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group. Lancet Neurol. 2021;20(6):484–496. doi: 10.1016/S1474-4422(21)00066-1

[20] Dubois B., Villain N., Frisoni G.B., et al. Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group // Lancet Neurol. 2021. Vol. 20, N 6. P. 484–496. doi: 10.1016/S1474-4422(21)00066-1

[21] Dubois B, Villain N, Frisoni GB, et al. Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group. Lancet Neurol. 2021;20(6):484–496. doi: 10.1016/S1474-4422(21)00066-1

[22] Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment. JAMA. 2014;312(23):2551–2561. doi: 10.1001/jama.2014.13806

[23] Langa K.M., Levine D.A. The diagnosis and management of mild cognitive impairment // JAMA. 2014. Vol. 312, 23. P. 2551–2561. doi: 10.1001/jama.2014.13806

[24] Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment. JAMA. 2014;312(23):2551–2561. doi: 10.1001/jama.2014.13806

[25] Ritchie LJ, Tuokko H. Patterns of cognitive decline, conversion rates, and predictive validity for 3 models of MCI. Am J Alzheimer’s Dis Other Dementiasr. 2010;25(7):592–603. doi: 10.1177/1533317510382286

[26] Ritchie L.J., Tuokko H. Patterns of cognitive decline, conversion rates, and predictive validity for 3 models of MCI // Am. J. Alzheimer’s Dis. Other Dementiasr. 2010. Vol. 25, N 7. P. 592–603. doi: 10.1177/1533317510382286

[27] Ritchie LJ, Tuokko H. Patterns of cognitive decline, conversion rates, and predictive validity for 3 models of MCI. Am J Alzheimer’s Dis Other Dementiasr. 2010;25(7):592–603. doi: 10.1177/1533317510382286

[28] Blennow K, Shaw LM, Stomrud E et al. Predicting clinical decline and conversion to Alzheimer’s disease or dementia using novel Elecsys Aβ(1-42), pTau and tTau CSF immunoassays. Sci Rep. 2019;9(1):19024. doi: 10.1038/s41598-019-54204-z

[29] Blennow K., Shaw L.M., Stomrud E., et al. Predicting clinical decline and conversion to Alzheimer’s disease or dementia using novel Elecsys Aβ(1–42), pTau and tTau CSF immunoassays // Sci. Rep. 2019. Vol. 9, N 1. P. 19024. doi: 10.1038/s41598-019-54204-z

[30] Blennow K, Shaw LM, Stomrud E et al. Predicting clinical decline and conversion to Alzheimer’s disease or dementia using novel Elecsys Aβ(1-42), pTau and tTau CSF immunoassays. Sci Rep. 2019;9(1):19024. doi: 10.1038/s41598-019-54204-z

[31] Xiong X, He H, Ye Q, et al. Alzheimer’s disease diagnostic accuracy by fluid and neuroimaging ATN framework. CNS Neurosci Ther. 2024;30(2): e14357. doi: 10.1111/cns.14357

[32] Xiong X., He H., Ye Q., et al. Alzheimer’s disease diagnostic accuracy by fluid and neuroimaging ATN framework // CNS Neurosci. Ther. 2024; Vol. 30, N 2. P. e14357. doi: 10.1111/cns.14357

[33] Xiong X, He H, Ye Q, et al. Alzheimer’s disease diagnostic accuracy by fluid and neuroimaging ATN framework. CNS Neurosci Ther. 2024;30(2): e14357. doi: 10.1111/cns.14357

[34] Caminiti SP, Ballarini T, Sala A, et al. FDG-PET and CSF biomarker accuracy in prediction of conversion to different dementias in a large multicentre MCI cohort. Neuroimage Clin. 2018;18:167–177. doi: 10.1016/j.nicl.2018.01.019

[35] Caminiti S.P., Ballarini T., Sala A., et al. FDG-PET and CSF biomarker accuracy in prediction of conversion to different dementias in a large multicentre MCI cohort // Neuroimage Clin. 2018. Vol. 18. P. 167–177. doi: 10.1016/j.nicl.2018.01.019

[36] Caminiti SP, Ballarini T, Sala A, et al. FDG-PET and CSF biomarker accuracy in prediction of conversion to different dementias in a large multicentre MCI cohort. Neuroimage Clin. 2018;18:167–177. doi: 10.1016/j.nicl.2018.01.019

[37] Levin F, Ferreira D, Lange C, et al. Data-driven FDG-PET subtypes of Alzheimer’s disease-related neurodegeneration. Alzheimers Res Ther. 2021; 13: 49. doi: 10.1186/s13195-021-00785-9

[38] Levin F., Ferreira D., Lange C., et al. Data-driven FDG-PET subtypes of Alzheimer’s disease-related neurodegeneration // Alzheimers Res. Ther. 2021. Vol. 13, N 1. P. 49. doi: 10.1186/s13195-021-00785-9

[39] Levin F, Ferreira D, Lange C, et al. Data-driven FDG-PET subtypes of Alzheimer’s disease-related neurodegeneration. Alzheimers Res Ther. 2021; 13: 49. doi: 10.1186/s13195-021-00785-9

[40] Lobzin VYu. Comprehensive early diagnostics of cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2015;115(11): 72–79. (In Russ.) EDN: VHCXGP doi: 10.17116/jnevro201511511172-79

[41] Лобзин В.Ю. Комплексная ранняя диагностика нарушений когнитивных функций // Журнал неврологии и психиатрии им. C.C. Корсакова. 2015. Т. 115, № 11. С. 72–79. EDN: VHCXGP doi: 10.17116/jnevro201511511172-79

[42] Lobzin VYu. Comprehensive early diagnostics of cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2015;115(11): 72–79. (In Russ.) EDN: VHCXGP doi: 10.17116/jnevro201511511172-79

[43] Emelin AYu, Odinak MM, Lobzin VYu, et al. Current capacities for neuroimaging in the differential diagnosis of cognitive impairments. Neurology, Neuropsychiatry, Psychosomatics. 2012;(S2):51–55. (In Russ.) EDN: PHCXDZ doi: 10.14412/2074-2711-2012-2509

[44] Емелин А.Ю., Одинак М.М., Лобзин В.Ю., и др. Современные возможности нейровизуализации в дифференциальной диагностике когнитивных нарушений // Неврология, нейропсихиатрия, психосоматика. 2012. № S2. С. 51–55. EDN: PHCXDZ doi: 10.14412/2074-2711-2012-2509

[45] Emelin AYu, Odinak MM, Lobzin VYu, et al. Current capacities for neuroimaging in the differential diagnosis of cognitive impairments. Neurology, Neuropsychiatry, Psychosomatics. 2012;(S2):51–55. (In Russ.) EDN: PHCXDZ doi: 10.14412/2074-2711-2012-2509

[46] Lupanov IA. Positron emission tomography imaging in early verification of Alzheimer’s disease and vascular cognitive impairment. Bulletin of the Russian Military Medical Academy. 2014;(1(45)):40–45. (In Russ.) EDN: RYCBQJ

[47] Лупанов И.А. Применение позитронной эмиссионной томографии в ранней диагностике болезни Альцгеймера и сосудистых когнитивных нарушений // Вестник Российской военно-медицинской академии. 2014. № 1 (45). С. 40–45. EDN: RYCBQJ

[48] Lupanov IA. Positron emission tomography imaging in early verification of Alzheimer’s disease and vascular cognitive impairment. Bulletin of the Russian Military Medical Academy. 2014;(1(45)):40–45. (In Russ.) EDN: RYCBQJ

[49] Petersen R, Touchon J. Consensus on mild cognitive impairment: EADS–ADCS. Research and Practice in Alzheimer’s Disease. 2005; 10:38–46.

[50] Petersen R., Touchon J. Consensus on mild cognitive impairment: EADS–ADCS // Research and Practice in Alzheimer’s Disease. 2005. Vol. 10. P. 38–46.

[51] Petersen R, Touchon J. Consensus on mild cognitive impairment: EADS–ADCS. Research and Practice in Alzheimer’s Disease. 2005; 10:38–46.

[52] Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS–AIREN International workshop. Neurology. 1993;43(2): 250–260. doi: 10.1212/wnl.43.2.250

[53] Roman G.C., Tatemichi T.K., Erkinjuntti T., et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS–AIREN International workshop // Neurology. 1993. Vol. 43, N 2. P. 250–260. doi: 10.1212/wnl.43.2.250

[54] Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS–AIREN International workshop. Neurology. 1993;43(2): 250–260. doi: 10.1212/wnl.43.2.250

[55] Stanzhevsky AA, Tyutin LA, Kostenikov NA. The possibilities of positron emission tomography in complex diagnosis and differential diagnosis of different nosological forms of dementia. Radiation diagnostics and therapy. 2011;(1(2)):55–63. (In Russ.) EDN: NUUOAR

[56] Станжевский А.А., Тютин Л.А., Костеников Н.А. Возможности позитронно-эмиссионной томографии в комплексной и дифференциальной диагностике различных нозологических форм деменции // Лучевая диагностика и терапия. 2011. № 1 (2). С. 55–63. EDN: NUUOAR

[57] Stanzhevsky AA, Tyutin LA, Kostenikov NA. The possibilities of positron emission tomography in complex diagnosis and differential diagnosis of different nosological forms of dementia. Radiation diagnostics and therapy. 2011;(1(2)):55–63. (In Russ.) EDN: NUUOAR

[58] 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. PMID: 15073255

[59] Silverman D.H.S. 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. Vol. 45, N 4. P. 594–607. PMID: 15073255

[60] 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. PMID: 15073255

[61] Kerrouche N, Herholz K, Mielke R, et al. 18FDG PET in vascular dementia: differentiation from Alzheimer’s disease using voxel-based multivariate analysis. J Cereb Blood Flow Metab. 2006;26(9): 1213–1221. doi: 10.1038/sj.jcbfm.9600296

[62] Kerrouche N., Herholz K., Mielke R., et al. 18FDG PET in vascular dementia: differentiation from Alzheimer’s disease using voxel-based multivariate analysis // J. Cereb. Blood Flow Metab. 2006. Vol. 26, N 9. P. 1213–1221. doi: 10.1038/sj.jcbfm.9600296

[63] Kerrouche N, Herholz K, Mielke R, et al. 18FDG PET in vascular dementia: differentiation from Alzheimer’s disease using voxel-based multivariate analysis. J Cereb Blood Flow Metab. 2006;26(9): 1213–1221. doi: 10.1038/sj.jcbfm.9600296

[64] Kaneta T, Okamura N, Arai A, et al. Analysis of early phase [11C] BF-227 PET, and its application for anatomical standardization of late-phase images for 3D-SSP analysis. Japanese J Radiol. 2014;32(3):1–7. doi: 10.1007/s11604-013-0276-7

[65] Kaneta T., Okamura N., Arai A., et al. Analysis of early phase [11C] BF-227 PET, and its application for anatomical standardization of late-phase images for 3D-SSP analysis // Japanese J. Radiol. 2014. Vol. 32, N 3. P. 1–7. doi: 10.1007/s11604-013-0276-7

[66] Kaneta T, Okamura N, Arai A, et al. Analysis of early phase [11C] BF-227 PET, and its application for anatomical standardization of late-phase images for 3D-SSP analysis. Japanese J Radiol. 2014;32(3):1–7. doi: 10.1007/s11604-013-0276-7

[67] Schöll M, Almkvist O, Axelman K, et al. Glucose metabolism and PIB binding in carriers of His163Tyr presenilin 1 mutation. Neurobiol Aging. 2011;32(8):1388–1399. doi: 10.1016/j.neurobiolaging.2009.08.016

[68] Schöll M., Almkvist O., Axelman K., et al. Glucose metabolism and PIB binding in carriers of His163Tyr presenilin 1 mutation // Neurobiol. Aging. 2011. Vol. 32, N 8. P. 1388–1399. doi: 10.1016/j.neurobiolaging.2009.08.016

[69] Schöll M, Almkvist O, Axelman K, et al. Glucose metabolism and PIB binding in carriers of His163Tyr presenilin 1 mutation. Neurobiol Aging. 2011;32(8):1388–1399. doi: 10.1016/j.neurobiolaging.2009.08.016

[70] Mosconi L, De Santi S, Brys M, et al. Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. Biol Psychiatry. 2008;63(9): 609–618. doi: 10.1016/j.biopsych.2007.05.030

[71] Mosconi L., De Santi S., Brys M., et al. Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints // Biol. Psychiatry. 2008. Vol. 63, N 6. P. 609–618. doi: 10.1016/j.biopsych.2007.05.030

[72] Mosconi L, De Santi S, Brys M, et al. Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. Biol Psychiatry. 2008;63(9): 609–618. doi: 10.1016/j.biopsych.2007.05.030

[73] Mosconi L, Brys M, Switalski R, et al. Maternal family history of Alzheimer’s disease predisposes to reduced brain glucose metabolism. Proc Natl Acad Sci USA. 2007;104(48):19067–19072. doi: 10.1073/pnas.0705036104

[74] Mosconi L., Brys M., Switalski R., et al. Maternal family history of Alzheimer’s disease predisposes to reduced brain glucose metabolism // Proc. Natl. Acad. Sci. USA. 2007. Vol. 104, N 48. P. 19067–19072. doi: 10.1073/pnas.0705036104

[75] Mosconi L, Brys M, Switalski R, et al. Maternal family history of Alzheimer’s disease predisposes to reduced brain glucose metabolism. Proc Natl Acad Sci USA. 2007;104(48):19067–19072. doi: 10.1073/pnas.0705036104

[76] Gordon BA, Blazey TM, Su Y, et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: A longitudinal study. Lancet Neurol. 2018;17(3):241–250. doi: 10.1016/S1474-4422(18)30028-0

[77] Gordon B.A., Blazey T.M., Su Y., et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: A longitudinal study // Lancet Neurol. 2018. Vol. 17, N 3. P. 241–250. doi: 10.1016/S1474-4422(18)30028-0

[78] Gordon BA, Blazey TM, Su Y, et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: A longitudinal study. Lancet Neurol. 2018;17(3):241–250. doi: 10.1016/S1474-4422(18)30028-0

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