Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published 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

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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2007

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239–59.PubMedCrossRef
2.
Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 1999;45:358–68.PubMedCrossRef
3.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edn. Washington, D.C.: American Psychiatric Association; 1994.
22.
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.
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.
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.
Lezak MD. Neuropsychological assessment, 3rd edn. New York: Oxford University Press; 1995.
26.
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.
Woods RP, Mazziotta JC, Cherry SR. MRI-PET registration with automated algorithm. J Comput Assist Tomogr 1993;17:536–46.PubMedCrossRef
28.
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.
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.
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.
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.
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.
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.
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
Metadata
Title
Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer’s disease
Authors
Lisa Mosconi
Wai H. Tsui
Henry Rusinek
Susan De Santi
Yi Li
Gene-Jack Wang
Alberto Pupi
Joanna Fowler
Mony J. de Leon
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-007-0406-5

Other articles of this Issue 9/2007

European Journal of Nuclear Medicine and Molecular Imaging 9/2007 Go to the issue

Letter to the editor

Administering radioiodine treatment; alternative to nuclear medicine prescribing

Original Article

Accuracy of 3D acquisition mode for myocardial FDG PET studies using a BGO-based scanner

Original article

Regional CBF changes in Parkinson’s disease: a correlation with motor dysfunction

Original article

Development of a cost-effective modular SPECT/CT scanner

Original Article

Diagnostic accuracy of FDG PET in the follow-up of platinum-sensitive epithelial ovarian carcinoma

Original article

Direct comparison of [18F]FDG PET/CT with PET alone and with side-by-side PET and CT in patients with malignant melanoma