Summary
Resting glucose metabolism in the association neocortices, measured with positron emission tomography (PET), is disturbed early and throughout the course of Alzheimer’s disease (AD), whereas resting metabolism in the primary sensory and motor neocortices is relatively spared. Neocortical metabolic asymmetries precede and predict appropriate deficits in neocortically-mediated cognitive functions in the initial course of disease, Indicating that PET can be used for the early diagnosis and characterization of AD. Metabolic abnormalities of the neocortices in late-stage AD correlate with regional densities of neurofibrillary tangles but not of senile plaques post mortem, suggesting that tangle formation is important in disease pathogenesis.
Despite demonstrating reduced resting glucose metabolism, visual association areas demonstrate equivalent (as percent baseline) blood flow responses in mildly-moderately demented AD patients and controls who are performing a face matching task. Thus, viability and integrity of this cortical circuitry is retained into the intermediate stages of the disease, and glucose delivery to the AD brain can be increased.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Abraham, C. R., Selkoe, D. J., and Potter, H., 1988, Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer’s disease, Cell, 52:487.
Ball, M. J., and Nuttall, K., 1981, Topography of neurofibrillary tangles and granulovacuoles in hippocampi of patients with Down’s syndrome: quantitative comparison with normal ageing and Alzheimer’s disease, Neuropathol. Appl. Neurobiol., 7: 13.
Ball, M. J., Fisman, M., Hachinski, V., Blume, W., Fox, A., Kral, V. A., Kirshen, A. J., Fox, H., and Merskey, H., 1985, A new definition of Alzheimer’s disease: a hippocampal dementia, Lancet, Jan., 14.
Benton, A., 1985, Visuoperceptual, visuospatial and visuoconstructive disorders, in: “Clinical Neuropsychology,” 2nd Ed., K. M. Heilman, E. Valenstein, eds., Oxford University Press, Oxford.
Blessed, B., Tomlinson, B. E., and Roth, M., 1968, The association between quantitative measures of dementia and of senile change in the cerebral gray matter of elderly subjects, Brit. J. Psychiatry 114:797.
Brun, A., and Gustafson, L., 1976, Distribution of cerebral degeneration in Alzheimer’s disease. A clinico-pathological study, Arch. Psychiatr. Nervenkr. 223: 15.
Casanova, M. F., Walker, L. C., Whitehouse, P. J., and Price, D. L., 1985, Abnormalities of the nucleus basalis in Down’s syndrome, Ann. Neurol. 18:310.
Creasey, H., Schwartz, M., Frederickson, H., Haxby, J. V., and Rapoport, S. I., 1986, Quantitative computed tomography in dementia of the Alzheimer type, Neurology 36: 1563.
DeCarli, C., Atack, J. R., Ball, M. J., Kaye, J. A., Grady, C. L., Fewster, P., Katz, D., Schapiro, M. B., and Rapoport, S. I., in preparation, Regional neurofibrillary tangle densities, but not regional senile plaque densities, correlate with regional reductions in cerebral glucose utilization during life in Alzheimer disease patients.
Delaere, P., Duyckaerts, C., Brion, J. B., Poulain, V., Hauw, J. J., 1989, Tau, paired helical filaments and amyloid in the neocortex: a morphometric study of 15 cases with graded intellectual status in aging and senile dementia of the Alzheimer type, Acta Neuropathol. (Berlin) 77:645.
Duara, R., Grady, C. L., Haxby, J. V., Sundaram, M., Cutler, N. R., Heston, L., Moore, A., Schlageter, N. L., Larson, S., and Rapoport, S. I., 1986, Positron emission tomography in Alzheimer’s disease, Neurology 36:879.
Duyckaerts, C., Hauw, J. J., Piette, F., Rainsard, C., Poulain, V., Berthaux, P., and Escourolle, R., 1985, Cortical atrophy in senile dementia of the Alzheimer type is mainly due to a decrease in cortical length, Acta Neuropathol. (Berl.) 66:72.
Folstein, M. F., Folstein, S. E., and McHugh, P. R., 1975, “Mini-Mental State.” A practical method for grading the cognitive state of patients for the clinician, J. Psychiat. Res. 12:189.
Foster, N. L., Chase, T. N., Mansi, L., Brooks, R., Fedio, P., Patronas, N. J., and Di Chiro, G., 1984, Cortical abnormalities in Alzheimer’s disease, Ann. Neurol. 16:649.
Friedland, R. P., Budinger, T. F., Koss, E., and Ober, B. A., 1985, Alzheimer’s disease: anterior-posterior and lateral hemispheric alterations in cortical glucose utilization, Neurosci. Lett. 53:235.
Friedland, R. P., Koss, E., Haxby, J. V., Grady, C. L., Luxenberg, J., Schapiro, M. B., and Kaye, J., 1988, Alzheimer disease: clinical and biological heterogeneity, Ann. Int. Med. 109:298.
Friedland, R. P., Jagust, W. J., Huesman, R. H., Koss, E., Knittel, B., Mathis, C. A., Ober, B. A., Mazoyer, B. M., and Budinger, T. F., 1989, Regional cerebral glucose transport and utilization in Alzheimer’s disease, Neurology 39:1427.
Fukuyama, H., Kameyama, M., Harada, K., Nishizawa, S., Senda, M., Mukai, T., Yonekura, Y., and Torizuka, K., 1989, Glucose metabolism and rate constants in Alzheimer’s disease examined with dynamic positron emission tomography scan, Acta Neurol. Scand. 80:307.
Gjedde, A., 1983, Modulation of substrate transport to the brain, Acta Neurol. Scand. 67:3.
Gjedde, A., and Crone, C., 1981, Blood-brain glucose transfer: repression in chronic hyperglycemia, Science 214:456.
Glenner, G. G., 1985, On causative theories in Alzheimer’s disease, Hum. Pathol. 16:433.
Grady, C., Haxby, J., Horwitz, B., Schapiro, M., Carson, R., Herscovitch, P., and Rapoport, S. I., 1990, Activation of regional cerebral blood flow (rCBF) in extrastriate cortex during a face matching task in patients with dementia of the Alzheimer type (DAT), Soc. Neurosci. Abstr.
Grady, C. L., Haxby J. V., Horwitz, B., Sundaram, M., Berg, G., Schapiro, M., Friedland, R. P., and Rapoport, S.I., 1988, A longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type, J. Clin. Exp. Neuropsychol. 10:576.
Grady, C. L., Haxby, J., Schapiro, M. B., Kumar, A., Friedland, R. P. and Rapoport, S. I., 1989, Heterogeneity in dementia of the Alzheimer type (DAT): subgroups identified from cerebral metabolic patterns using positron emission tomography (PET), Neurology 39(Suppl. 1):167.
Grady, C. L., Haxby, J. V., Schlageter, N. L., Berg, G., and Rapoport, S. I., 1986, Stability of metabolic and neuropsychological asymmetries in dementia of the Alzheimer type, Neurology 36:1390.
Grundke-Iqbal, I., Iqbal, K., Tung, Y.-C., Quinlan, M., Wisniewski, H.M., and Binder, L. I., 1986, Abnormal phosphorylation of the microtubule-associated protein x (tau) in Alzheimer cytoskeletal pathology, Proc. Natl. Acad. Sci. (USA). 83:4913.
Hardy, J. A., Mann, D. M. A., Wester, P., and Winbland, B., 1986, An integrative hypothesis concerning the pathogenesis and progression of Alzheimer’s disease, Neurobiol. Aging 7:489.
Haxby, J. V., 1986, Cerebral metabolic rate of glucose and Alzheimer’s disease: Reply, J. Cereb. Blood Flow Metab. 6:125.
Haxby, J. V., Duara, R., Grady, C. L., Cutler, N. R., and Rapoport, S. I., 1985, Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer’s disease, J. Cereb. Blood Flow Metab. 5:193.
Haxby, J. V., Grady, C. L., Duara, R., Schlageter, N., Berg, G., and Rapoport, S. I., 1986, Neocortical metabolic abnormalities precede non-memory cognitive deficits in early Alzheimer’s-type dementia, Arch. Neurol. 43:882.
Haxby, J. V., Grady, C. L., Friedland, R. P., and Rapoport, S. I., 1987, Neocortical metabolic abnormalities precede nonmemory cognitive impairments in early dementia of the Alzheimer type, J. Neural Transmission, 24 (Suppl):49.
Haxby, J. V., Grady, C. L., Horwitz, B., Schapiro, M. B., Carson, R. E., Ungerleider, L. G., Mishkin, M., Herscovitch, P., Friedland, R. P. and Rapoport, S. I., 1988, Mapping two visual pathways in man with regional cerebral blood flow (rCBF) as measured by positron emission tomography and H215O, Soc. Neurosci. Abstr., 14:750.
Haxby, J. V., Grady, C. L., Koss, E., Horwitz, B., Schapiro, M. B., Katz, D., Friedland, R. P., and Rapoport, S. I., in press, Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological deficits in early dementia of the Alzheimer type.
Heston, L. L., Mastri, A. R., Anderson, V. E., and White, J., 1981, Dementia of the Alzheimer type. Clinical genetics, natural history, and associated conditions, Arch. Gen. Psychiatry 38:1085.
Horwitz, B., Grady C. L., Schlageter, N. L., Duara, R., and Rapoport, S. I., 1987, Intercorrelations of regional cerebral glucose metabolic rates in Alzheimer’s disease, Brain Res. 407:294.
Huang, S.-C, Phelps, M. E., Hoffman, E. J., Sideris, K., Selin, C. J., and Kuhl, D. E., 1980, Non-invasive determination of local cerebral metabolic rate of glucose in man, Am. J. Physiol. 238:E69.
Hyman, B. T., Van Hoesen, G. W., Damasio A. R., and Barnes, C. L., 1984, Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation, Science (Wash.) 225: 1168.
Hyman, B. T., Van Hoesen, G. W., Kromer, L. J., and Damasio, A. R., 1986, Perforant pathway changes and the memory impairment of Alzheimer’s disease, Ann. Neurol. 20:472.
Kalaria, R. N., and Harik, S. I., 1988, Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer disease, J. Neurochem. 53: 1083.
Kessler, R. M., Goble, J. C., Bird, J. H., Girton, M. E., Doppman, J. L., Rapoport, S. I., and Barranger, J. A., 1984, Measurement of blood-brain barrier permeability with positron emission tomography and 68Ga EDTA., J. Cerebral Blood Flow Metab., 4:323.
King, M.-C., Wilson, A. C., 1975, Evolution at two levels in humans and chimpanzees, Science (Wash.) 188: 107.
Lewis, D. A., Campbell, M. J., Terry, R. D., and Morrison, J. H., 1987, Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer’s disease: a quantitative study of visual and auditory cortices, J. Neurosci. 7:1799.
Luxenberg, J. S., Haxby, J. V., Creasey, H., Sundaram, M., and Rapoport, S. I., 1987, Rate of ventricular enlargement in dementia of the Alzheimer type correlates with rate of neuropsychological deterioration, Neurology 37: 1135.
Mann, D. M., Marcyniuk, B., Yates, P. D., Neary, D., and Snowden, J. S., 1988, The progression of the pathological changes of Alzheimer’s disease in frontal and temporal neocortex examined both at biopsy and at autopsy, Neuropathol. Appl. Neurobiol. 14: 177.
Mann, D. M. A., Yates, P. O., and Marcyniuk, B., 1984, Alzheimer’s presenile dementia, senile dementia of Alzheimer type and Down’s syndrome in middle age form an age related continuum of pathological changes, Neuropathol. Appl. Neurobiol. 10: 185.
Mann, D. M. A., Yates P. O., and Marcyniuk, B., 1985, Correlation between senile plaque and neurofibrillary tangle counts in cerebral cortex and neuronal counts in cortex and subcortical structures. Neurosci. Lett. 56:51.
McCall, A. L., Fixman, L. B., Tornheim, K., Chick, W., and Ruderman, N. B., 1986, Chronic hypoglycemia increases brain glucose transport, Am. J. Physiol. 251:E442.
McGeer, P. L., Kamo, H., Harrop, R., McGeer, E. G., Martin, W. R. W., Pate, B. D., and Li, D. K. B., 1986, Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer’s disease. Neurology 36: 1569.
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., and Stadlan, E. M., 1984, 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 34:939.
Metter, E. J., Riege, W. H., Kameyama, M., Kuhl, D. E., and Phelps, M. E., 1984, Cerebral metabolic relationships for selected brain regions in Alzheimer’s, Huntington’s, and Parkinson s diseases, J. Cereb. Blood Flow Metab. 4:500.
Miller, J. D., De Leon, M. J., Ferris, S. H., Kluger, A., George, A. E., Reisberg, B., Sachs, H. J., and Wolf, A. P., 1987, Abnormal temporal lobe response in Alzheimer’s disease during cognitive processing as measured by 11C-2-deoxy-D-glucose and PET. J. Cerebral Blood Flow Metab., 7:248.
Mishkin, M., Ungerleider, L. G., and Macko, K. A., 1983, Object vision and spatial vision: two cortical pathways. Trends Neurosci., 6:414.
Morrison, J. H., Lewis, D. A., Campbell, M. J., Huntley, G. W., Benson, D. L., and Bouras, C., 1987, A monoclonal antibody to non-phosphorylated neurofilament protein marks the vulnerable cortical neurons in Alzheimer’s disease, Brain Res. 416:331.
Najlerahim, A., and Bowen, D. M., 1988, Regional weight loss of the cerebral cortex and some subcortical nuclei in senile dementia of the Alzheimer type, Acta Neuropathol. (Berl.) 75:509.
Neary, D., Snowden, J. S., Mann, D. M. A., Bowen, D. M., Sims, N. R., Northern, B., Yates, P. O., and Davison, A. N., 1986, Alzheimer’s disease: a correlative study. J. Neurol. Neurosurg. Psychiatry 49:229.
Palmert, M. r., Golde, T. E., Cohen, M. L., Kovacs, D. M., Tanzi, R. E., Gusella, J. F., Usiak, M. F., Younkin, L. H., and Younkin, S. G., 1988, Amyloid protein precursor messenger RNAs: differential expression in Alzheimer’s disease. Science 241:1080.
Pandya, D. N., and Seltzer, B., 1982, Association areas of the cerebral cortex, Trends Neurosci. 5:386.
Pardridge, W. M., In Press, Blood-brain barrier transport of glucose, ketone bodies and free fatty acids, In “1st Toronto-Stockholm Symposium on Perspectives in Diabetes Research, The Nervous System and Fuel Homeostasis,” Plenum Press, New York.
Pearson, R. C., Esiri, M. M., Hiorns, R. W., Wilcock, G. K., and Powell, T. P. S., 1985, Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer’s disease, Proc. Natl. Acad. Sci. (USA) 82:4531.
Raichle, M. E., In Press, Nonoxidative glucose consumption and normal brain function -positron emission tomography studies in normal humans, In “1st Toronto-Stockholm Symposium on Perspectives in Diabetes Research, The Nervous System and Fuel Homeostasis,” Plenum Press, New York.
Rapoport, S. I., 1988a, Brain evolution and Alzheimer’s disease, Rev. Neurol. 144:79.
Rapoport, S. I., 1988b, A phylogenetic hypothesis for Alzheimer’s disease, in: “Genetics and Alzheimer s Disease. Research and Perspectives in Alzheimer’s Disease,” P. M. Sinet, Y. Lamour and Y. Christen, eds., Fondation Ipsen, Springer-Verlag, Berlin.
Rapoport, S. I., 1989, Hypothesis: Alzheimer’s disease is a phylogenetic disease, Med. Hypotheses 29: 147.
Rapoport, S. I., and Horwitz, B., 1989, Use of positron emission tomography to study patterns of brain metabolism in relation to age and disease: a correlation matrix approach, in: “Regulatory Mechanisms of Neuron to Vessel Communication in the Brain,” F. Battaini, S. Govoni, M. S. Magnoni and M. Trabucci, eds., NATO Advanced Science Institute Series, Cell Biology, Vol 33, Springer-Verlag, Berlin.
Rapoport, S. I., Horwitz, B., Grady, C. L., and Haxby, J. V., 1987, Alzheimer s disease causes metabolic uncoupling of associative brain regions beyond that seen in the healthy elderly, in: “Modifications of Cell to Cell Signals During Normal and Pathological Aging,” S. Gouani and F. Battaini, eds., NATO ASI Series, Vol. H9, Springer-Verlag, Berlin.
Rapoport, S. I., Horwitz, B., Haxby, J. V., and Grady, C. L., 1986, Alzheimer s disease: metabolic uncoupling of associative brain regions, Can. J. Neurol Sci. 13:540.
Reivich, M., 1974, Blood flow metabolism coupling in brain, Res. Publ. Assoc. Res. Nerv. Ment. Dis. 53:125.
Rogers, J., and Morrison, J. H., 1985, Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer s disease, J. Neurosci. 5:2801.
Roses, A. D., Pericak-Vance, M. A., Haynes, C. S., Haines, J. L., Gaskell, P. A., Yamaoka, L. H., Hung, W-Y., Clark, C. M., Alberts, M. J., Lee, J. E., Siddique, T., and Heyman, A. L., 1988, Genetic linkage studies in Alzheimer’s disease (AD). Neurology 38(Suppl 1):173.
Schapiro, M. B., Haxby, J. V., Grady, C. L., Rapoport, S. I., 1986, Cerebral glucose utilization, quantitative tomography, and cognitive function in adult Down syndrome, in: “ The Neurobiology of Down Syndrome,” C. J. Epstein, ed., Raven Press, New York.
Schapiro, M. B., Luxenberg, J. S., Kaye, J. A., Haxby, J. V., Friedland, R. P., and Rapoport, S. I., 1989, Serial quantitative computed tomography analysis of brain morphometries in adult Down syndrome at different ages. Neurology 39:1349.
Schapiro, M. B., and Rapoport, S. I., 1988, Alzheimer’s disease in premorbidly normal and Down’s syndrome individuals: selective involvement of hippocampus and neocortical associative brain regions, Brain Dysfunction 1:2.
Schellenberg, G. D., Bird, T. D., Wijsman, E. M., Moore, D. K., Boenhnke, M., Bryant, E. M., Lampe, T. H., Nochlin, D., Sumi, S. M., Deeb, S. S., Beyreuther, K., and Martin, G. M., 1988, Absence of linkage of chromosome 21q21 markers to familial Alzheimer’s disease, Science (Wash.) 241:1507.
Schwartz, M. L., Goldman-Rakic, P. S., 1984, Callosal and intrahemispheric connectivity of the prefrontal association cortex in Rhesus monkey: relation between intraparietal and principal sulcal cortex, J. Comp. Neurol. 226:403.
Smith, L. S., Bottomley, P. A., Drayer, B. P. and Herfkens, R. J., 1986, Localized clinical 31P NMR sprectroscopy in Huntington’s, Parkinson’s, Alzheimer’s and Binswanger’s diseases, Abstr. Fifth Annual Meeting Soc. Magnetic Resonance in Medicine, August 19-22, 1986, Montreal, 4:1386.
Sokoloff, L., Reivich, M., Kennedy, C., Des Rosiers, M. H., Patlak, C. S., Pettigrew, K. D., Sakurada, O., and Shinohara, M., 1977, The [l4C]deoxyglucose methods for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized rat, J. Neurochem., 28:897.
St George-Hyslop, P. H., Tanzi, R. E., Polinsky, R. J., Haines, J. L., Nee, L., Watkins, P. C., Myers, R. H., Feldman, R. G., Pollen, D., Drachman, D., Growdon, J., Bruni, A., Foncin, J.-F., Salmon, D., Frommelt, P., Amaducci, L., Sorbi, S., Piacentini, S., Stewart, G. D., Hobbs, W. J., Conneally, P. M., and Gusella, J. F., 1987, The genetic defect causing familial Alzheimer’s disease maps on chromosome 21, Science (Wash.) 235:885.
Van Hoesen, G. W., 1982, The primate parahippocampal gyrus: new insights regarding its cortical connections, Trends Neurosci. 5:345.
Wilcock, G. K., and Esiri, M. M., 1982, Plaques, tangles and dementia: a quantitative study, J. Neurol. Sci. 56:343.
Wise, S. P., and Jones, E. P., 1977, Cells of origin and terminal distribution of descending projections of the rat somatic sensory cortex, J. Comp. Neurol. 175:129.
Wisniewski, K. E., Wisniewski, H. M., and Wen, G. Y., 1985, Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome, Ann. Neurol. 17:278.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Rapoport, S.I., Horwitz, B., Grady, C.L., Haxby, J.V., DeCarli, C., Schapiro, M.B. (1991). Abnormal Brain Glucose Metabolism in Alzheimer’s Disease, as Measured by Positron Emission Tomography. In: Vranic, M., Efendic, S., Hollenberg, C.H. (eds) Fuel Homeostasis and the Nervous System. Advances in Experimental Medicine and Biology, vol 291. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5931-9_18
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5931-9_18
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5933-3
Online ISBN: 978-1-4684-5931-9
eBook Packages: Springer Book Archive