Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 9/2007

01.09.2007 | Original article

Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer’s disease

verfasst von: Lisa Mosconi, Wai H. Tsui, Henry Rusinek, Susan De Santi, Yi Li, Gene-Jack Wang, Alberto Pupi, Joanna Fowler, Mony J. de Leon

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 9/2007

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To examine CMRglc measures and corresponding glucose transport (K 1 and k 2) and phosphorylation (k 3) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer’s disease (AD).

Methods

Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 ± 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 ± 9 years, three females, median MMSE 30). Absolute CMRglc (μmol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff’s autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined.

Results

With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k 3 reductions were found in the hippocampus, PCC and amygdala. K 1 reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures.

Conclusion

CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239–59.PubMedCrossRef Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239–59.PubMedCrossRef
2.
Zurück zum Zitat Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 1999;45:358–68.PubMedCrossRef Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 1999;45:358–68.PubMedCrossRef
3.
Zurück zum Zitat Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991;30:572–80.PubMedCrossRef Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991;30:572–80.PubMedCrossRef
4.
Zurück zum Zitat Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impiarment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1133–42.PubMed Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impiarment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1133–42.PubMed
5.
Zurück zum Zitat De Santi S, de Leon MJ, Rusinek H, Convit A, Tarshish CY, Boppana M, et al. Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging 2001;22:529–39.PubMedCrossRef De Santi S, de Leon MJ, Rusinek H, Convit A, Tarshish CY, Boppana M, et al. Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging 2001;22:529–39.PubMedCrossRef
6.
Zurück zum Zitat de Leon MJ, Convit A, Wolf OT, Tarshish CY, DeSanti S, Rusinek H, et al. Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET). Proc Natl Acad Sci USA 2001;98:10966–71.PubMedCrossRef de Leon MJ, Convit A, Wolf OT, Tarshish CY, DeSanti S, Rusinek H, et al. Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET). Proc Natl Acad Sci USA 2001;98:10966–71.PubMedCrossRef
7.
Zurück zum Zitat Nestor PJ, Fryer TD, Smielewski P, Hodges JR. Limbic hypometabolism in Alzheimer’s disease and mild cognitive impairment. Ann Neurol 2003;54:343–51.PubMedCrossRef Nestor PJ, Fryer TD, Smielewski P, Hodges JR. Limbic hypometabolism in Alzheimer’s disease and mild cognitive impairment. Ann Neurol 2003;54:343–51.PubMedCrossRef
8.
Zurück zum Zitat Mosconi L, Tsui WH, De Santi S, Li J, Rusinek H, Convit A, et al. Reduced hippocampal metabolism in mild cognitive impairment and Alzheimer’s disease: automated FDG-PET image analysis. Neurology 2005;64:1860–7.PubMedCrossRef Mosconi L, Tsui WH, De Santi S, Li J, Rusinek H, Convit A, et al. Reduced hippocampal metabolism in mild cognitive impairment and Alzheimer’s disease: automated FDG-PET image analysis. Neurology 2005;64:1860–7.PubMedCrossRef
9.
Zurück zum Zitat Mosconi L, De Santi S, Li Y, Li J, Zhan J, Tsui WH, et al. Visual rating of medial temporal lobe metabolism in mild cognitive impairment and Alzheimer’s disease using FDG-PET. Eur J Nucl Med 2006;33:210–21.CrossRef Mosconi L, De Santi S, Li Y, Li J, Zhan J, Tsui WH, et al. Visual rating of medial temporal lobe metabolism in mild cognitive impairment and Alzheimer’s disease using FDG-PET. Eur J Nucl Med 2006;33:210–21.CrossRef
10.
Zurück zum Zitat Mosconi L, Sorbi S, de Leon MJ, Li Y, Nacmias B, Myoung PS, et al. Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer’s disease. J Nucl Med 2006;47:1778–86.PubMed Mosconi L, Sorbi S, de Leon MJ, Li Y, Nacmias B, Myoung PS, et al. Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer’s disease. J Nucl Med 2006;47:1778–86.PubMed
11.
Zurück zum Zitat 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;42:85–94.PubMedCrossRef 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;42:85–94.PubMedCrossRef
12.
Zurück zum Zitat Chetelat G, Desgranges B, De La Sayette V, Viader F, Eustache F, Baron JC. Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer’s disease? Neurology 2003;60:1374–7.PubMed Chetelat G, Desgranges B, De La Sayette V, Viader F, Eustache F, Baron JC. Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer’s disease? Neurology 2003;60:1374–7.PubMed
13.
Zurück zum Zitat 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 2003;30:1104–13.CrossRef 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 2003;30:1104–13.CrossRef
14.
Zurück zum Zitat Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-flouro-2-deoxy-d-glucose:validation of method. Ann Neurol 1979;6:371–88.PubMedCrossRef Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-flouro-2-deoxy-d-glucose:validation of method. Ann Neurol 1979;6:371–88.PubMedCrossRef
15.
Zurück zum Zitat Patlak C, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983;3:1–7.PubMed Patlak C, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983;3:1–7.PubMed
16.
Zurück zum Zitat Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, et al. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 1977;28:897–916.PubMedCrossRef Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, et al. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 1977;28:897–916.PubMedCrossRef
17.
Zurück zum Zitat Reivich M, Alavi A, Wolf A, Fowler J, Russell J, Arnett C, et al. Glucose metabolic rate kinetic model parameter determination in humans: The lumped constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J Cereb Blood Flow Metab 1985;5:179–92.PubMed Reivich M, Alavi A, Wolf A, Fowler J, Russell J, Arnett C, et al. Glucose metabolic rate kinetic model parameter determination in humans: The lumped constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J Cereb Blood Flow Metab 1985;5:179–92.PubMed
18.
Zurück zum Zitat Friedland RP, Jagust WJ, Huesman RH, Koss E, Knittel B, Mathis CA, et al. Regional cerebral glucose transport and utilization in Alzheimer’s disease. Neurology 1989;39:1427–34.PubMed Friedland RP, Jagust WJ, Huesman RH, Koss E, Knittel B, Mathis CA, et al. Regional cerebral glucose transport and utilization in Alzheimer’s disease. Neurology 1989;39:1427–34.PubMed
19.
Zurück zum Zitat Jagust WJ, Seab JP, Huesman RH, Valk PE, Mathis CA, Reed BR, et al. Diminished glucose transport in Alzheimer’s disease: dynamic PET studies. J Cereb Blood Flow Metab 1991;11:323–30.PubMed Jagust WJ, Seab JP, Huesman RH, Valk PE, Mathis CA, Reed BR, et al. Diminished glucose transport in Alzheimer’s disease: dynamic PET studies. J Cereb Blood Flow Metab 1991;11:323–30.PubMed
20.
Zurück zum Zitat Piert M, Koeppe RA, Giordani B, Berent S, Kuhl DE. Diminished glucose transport and phosphorylation in Alzheimer’s disease determined by dynamic FDG-PET. J Nucl Med 1996;37:201–8.PubMed Piert M, Koeppe RA, Giordani B, Berent S, Kuhl DE. Diminished glucose transport and phosphorylation in Alzheimer’s disease determined by dynamic FDG-PET. J Nucl Med 1996;37:201–8.PubMed
21.
Zurück zum Zitat American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edn. Washington, D.C.: American Psychiatric Association; 1994. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edn. Washington, D.C.: American Psychiatric Association; 1994.
22.
Zurück zum Zitat 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;34:939–44.PubMed 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;34:939–44.PubMed
23.
Zurück zum Zitat Reisberg B, Ferris SH, de Leon MJ, Crook T. The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiat 1982;139:1136–9.PubMed Reisberg B, Ferris SH, de Leon MJ, Crook T. The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiat 1982;139:1136–9.PubMed
24.
Zurück zum Zitat Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98.PubMedCrossRef Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98.PubMedCrossRef
25.
Zurück zum Zitat Lezak MD. Neuropsychological assessment, 3rd edn. New York: Oxford University Press; 1995. Lezak MD. Neuropsychological assessment, 3rd edn. New York: Oxford University Press; 1995.
26.
Zurück zum Zitat Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001;32:1318–22.PubMed Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001;32:1318–22.PubMed
27.
Zurück zum Zitat Woods RP, Mazziotta JC, Cherry SR. MRI-PET registration with automated algorithm. J Comput Assist Tomogr 1993;17:536–46.PubMedCrossRef Woods RP, Mazziotta JC, Cherry SR. MRI-PET registration with automated algorithm. J Comput Assist Tomogr 1993;17:536–46.PubMedCrossRef
28.
Zurück zum Zitat Muller-Gartner HW, Links JM, Prince JL, Bryan RN, McVeigh E, Leal JP, et al. Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. J Cereb Blood Flow Metab 1992;12:571–83.PubMed Muller-Gartner HW, Links JM, Prince JL, Bryan RN, McVeigh E, Leal JP, et al. Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. J Cereb Blood Flow Metab 1992;12:571–83.PubMed
29.
Zurück zum Zitat Minoshima S, Frey KA, Foster NL, Kuhl DE. Preserved pontine glucose metabolism in Alzheimer’s disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr 1995;19:541–7.PubMedCrossRef Minoshima S, Frey KA, Foster NL, Kuhl DE. Preserved pontine glucose metabolism in Alzheimer’s disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr 1995;19:541–7.PubMedCrossRef
30.
Zurück zum Zitat Arnaiz E, Jelic V, Almkvist O, Wahlund LO, Winblad B, Valind S, et al. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. NeuroReport 2001;12:851–5.PubMedCrossRef Arnaiz E, Jelic V, Almkvist O, Wahlund LO, Winblad B, Valind S, et al. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. NeuroReport 2001;12:851–5.PubMedCrossRef
31.
Zurück zum Zitat Mosconi L, Perani D, Sorbi S, Herholz K, Nacmias B, Holthoff V, et al. MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology 2004;63:2332–40.PubMed Mosconi L, Perani D, Sorbi S, Herholz K, Nacmias B, Holthoff V, et al. MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology 2004;63:2332–40.PubMed
32.
Zurück zum Zitat Ishii K, Sasaki M, Kitagaki H, Yamaji S, Sakamoto S, Matsuda K, et al. Reduction of cerebellar glucose metabolism in advanced Alzheimer’s disease. J Nucl Med 1997;38:925–8.PubMed Ishii K, Sasaki M, Kitagaki H, Yamaji S, Sakamoto S, Matsuda K, et al. Reduction of cerebellar glucose metabolism in advanced Alzheimer’s disease. J Nucl Med 1997;38:925–8.PubMed
33.
Zurück zum Zitat Rapoport SI, Grady CL. Parametric in vivo brain imaging during activation to examine pathological mechanisms of functional failure in Alzheimer’s disease. Int J Neurosci 1993;70:36–59. Rapoport SI, Grady CL. Parametric in vivo brain imaging during activation to examine pathological mechanisms of functional failure in Alzheimer’s disease. Int J Neurosci 1993;70:36–59.
34.
Zurück zum Zitat Pietrini P, Furey ML, Alexander GE, Mentis MJ, Dani A, Guazzelli M, et al. Association between brain functional failure and dementia severity in Alzheimer’s disease: resting versus stimulation PET study. Am J Psychiatry 1999;156:470–3.PubMed Pietrini P, Furey ML, Alexander GE, Mentis MJ, Dani A, Guazzelli M, et al. Association between brain functional failure and dementia severity in Alzheimer’s disease: resting versus stimulation PET study. Am J Psychiatry 1999;156:470–3.PubMed
Metadaten
Titel
Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer’s disease
verfasst von
Lisa Mosconi
Wai H. Tsui
Henry Rusinek
Susan De Santi
Yi Li
Gene-Jack Wang
Alberto Pupi
Joanna Fowler
Mony J. de Leon
Publikationsdatum
01.09.2007
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 9/2007
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-007-0406-5

Weitere Artikel der Ausgabe 9/2007

European Journal of Nuclear Medicine and Molecular Imaging 9/2007 Zur Ausgabe