Alzheimer’s Disease Causes Metabolic Uncoupling of Associative Brain Regions Beyond that Seen in the Healthy Elderly

  • Stanley I. Rapoport
  • Barry Horwitz
  • C. L. Grady
  • J. V. Haxby
Part of the NATO ASI Series book series (volume 9)


Alzheimer’s disease (AD) is a progressive degenerative brain disorder that has no agreed-upon cause. The earliest and most prominent neuropsychological deficit is recent memory impairment, which usually is attributed to pathological and neurochemical changes in the hippocampus, amygdala and neocortex (3, 5, 32). The first cognitive deficits to appear that are related to neocortical dysfunction are impairments of attention, abstract reasoning, language and visuospatial construction (18, 20, 21).


Alzheimerrs Disease Positron Emission Tomography Alzheimerrs Disease Patient Demented Patient Association Cortex 
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  1. 1.
    Arendt, T., Bigl, V., Tennstedt, A., and Arendt, A., 1985, Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer’s disease, Neurosci., 14, 1–14.CrossRefGoogle Scholar
  2. 2.
    Axelrod, S., and Cohen, L. D., 1961, Senescence and embedded-figure performance in vision and touch. Percept. Motor Skills, 12, 283–288.Google Scholar
  3. 3.
    Ball, M. J., Fishman, M., Hachinski, V., Blume, W., Fox, A., Krai, V. A., Kirsher, A. J., Fox, H., and Merskey, H., 1985, A new definition of Alzheimer’s disease: a hippocampal dementia, Lancet, Jan., 14–16.Google Scholar
  4. 3a.
    Benton, A., 1985, Visuoperceptual, visuospatial and visuocontructive disorders, in: “Clinical Neuropsychology”, 2nd Ed., K. M. Heilman, E. Valenstein, eds., Oxford University Press, Oxford, pp. 151–186.Google Scholar
  5. 4.
    Birren, J. E., Butler, R. N., Greenhouse, S. W., Sokoloff, L., and Yarrow, M. R., 1963, Interdisciplinary relationships: interrelations of physiological, psychological, and pyschiatric findings in healthy elderly men, in: “Human Aging I: a Biological and Behavioral Approach”, J. E. Birren, R. N. Butler, S. W. Greenhouse, L. Sokoloff, M. R. Yarrow, eds., U. S. Government Printing Office, Washington, D. C. pp. 283–305CrossRefGoogle Scholar
  6. 5.
    Brun, A., and Gustafson L., 1976, Distribution of cerebral degeneration in Alzheimer’s disease. A clinico-pathological study, Arch. Psychiatr. Nervenkr., 223, 15–33.CrossRefGoogle Scholar
  7. 6.
    De Leon, M. J., Ferris, S. H., George, A. E., Reisberg, B., Christman, D. R., Kricheff, I. I., and Wolf, A. P., 1983, Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer’s disease. J. Cerebr. Blood Flow Metab., 3, 391–394.CrossRefGoogle Scholar
  8. 7.
    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. Neurol., 36, 879–887.Google Scholar
  9. 8.
    Duara, R., Grady, C. L., Haxby, J. V., Ingvar, D., Sokoloff, L., Margolin, R. A., Manning, R. G., Cutler, N. R., and Rapoport, S. I., 1984, Human brain glucose utilization and cognitive function in relation to age, Ann. Neurol., 16, 703–713.PubMedCrossRefGoogle Scholar
  10. 9.
    Duara, R., Margolin, R. A., Robertson-Tchabo, E. A., London, E. D., Schwartz, M., Renfrew, J. W., Koziarz, B. J., Sundaram, M., Grady, C., Moore, A. M., Ingvar, D. H., Sokoloff, L., Weingartner, H., Kessler, R. M., Manning, R. G., Channing, M. A., Cutler, N. R., and Rapoport, S. I., 1983, Cerebral glucose utilization, as measured with positron emission tomography in 21 resting healthy men between the ages of 21 and 83 years, Brain, 106, 761–775.PubMedCrossRefGoogle Scholar
  11. 10.
    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. Neuropath. (Berl), 66, 72–74.CrossRefGoogle Scholar
  12. 11.
    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, 189–198.PubMedCrossRefGoogle Scholar
  13. 12.
    Foster, N. L., Chase, T. N., Mansi, L., Brooks, R., Fedio, P., Patronas, N. J., and DiChiro, G., 1984, Cortical abnormalities in Alzheimer’s disease., Ann. Neurol., 16, 649–654.PubMedCrossRefGoogle Scholar
  14. 13.
    Frackowiak, R. S. J., Lenzi, G.-L., Jones, T., and Heather, J. D., 1980, Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 150 and positron emission tomography: theory, procedure and normal values, J. Comput. Asst. Tomog., 4, 727–736.CrossRefGoogle Scholar
  15. 14.
    Frackowiak, R., and Gibbs, J. M., 1983, Cerebral metabolism and blood flow in normal and pathologic aging, In: “Functional Radionuclide Imaging of the Brain”, P. Magistretti, ed, Raven Press, New York, pp. 305–309.Google Scholar
  16. 15.
    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, 235–240.Google Scholar
  17. 16.
    Gajdusek, D. C., 1985, Hypothesis: Interference with axonal transport of neurofilament as a common pathogenetic mechanism in certain diseases of the central nervous system, New Eng. J. Med., 312, 714–719.CrossRefGoogle Scholar
  18. 17.
    Goldman, P. S., and Nauta, W. J. H., 1977, Columnar distribution of cortico-cortical fibers in the frontal association, limbic, and motor cortex of the developing Rhesus monkey., Brain Res., 122, 393–413.PubMedCrossRefGoogle Scholar
  19. 18.
    Grady, C. L., Haxby, J. V., Sundaram, M., Berg, G., arid Rapoport, S. I., 1985, Longitudinal relations between cognitive and cerebral metabolic deficits in Alzheimer’s disease (AD)., J. Clin. Exp. Neuropsychol., 7, 622,Google Scholar
  20. 19.
    Grady, C. L., Haxby J. V., Schlageter, N. L., Berg, G., and Rapoport, S, I., in press, Stability of metabolic and neuropsychological asymmetries in dementia of the Alzheimer type, Neurol.Google Scholar
  21. 19a.Haxby, J. V., 1986, Cerebral metabolic rate of glucose and Alzheimer’s disease: Reply, J. Cerebr. Blood Flow Metabl., 6, 125–127.Google Scholar
  22. 20.
    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. Cerebr. Blood Flow Metab., 5, 193–200.CrossRefGoogle Scholar
  23. 21.
    Haxby, J. V., Grady, C. L., Duara, R., Schlageter, N., Berg, G., and Rapoport, S. I., in press, Neocortical metabolic abnormalities precede non-memory cognitive deficits in early Alzheimer-type dementia, Arch. Neurol Neurosurg. Psychiatr.Google Scholar
  24. 22.
    Horn, J. L., and Cattell, R. B., 1967, Age differences in fluid and crystallized intelligence, Acta Psychol. (Amst.), 26, 107–129.CrossRefGoogle Scholar
  25. 23.
    Horwitz, B., Grady C. L., Schlageter N. L., Duara, R., and Rapoport, S. I., in press, Intercorrelations of regional cerebral metabolic rates in Alzheimer’s disease, Brain Res.Google Scholar
  26. 24.
    Horwitz, B., Duara, R., and Rapoport S. I., 1986, Age differences in intercorrelations between regional cerebral metabolic rates for glucose, Ann Neurol., 19, 60–67.PubMedCrossRefGoogle Scholar
  27. 25.
    Horwitz, B., Duara, R., and Rapoport, S. I., 1984, Intercorrelations of glucose metabolic rates between brain regions: application to healthy males in a state of reduced sensory input, J. Cerebr. Blood Flow Metab., 4, 484–499.CrossRefGoogle Scholar
  28. 26.
    Huang, S-C, Phelps, M. E., Hoffman, E. J., Sideris, K., Selin, C. J., and Kuhl, D. E., 1980, Noninvasive determination of local cerebral metabolic rate of glucose in man., Am. J. Physiol., 238, E69–E82.PubMedGoogle Scholar
  29. 27.
    Hyman, B. T., Van Hoesen, G. W., Damasio A. R., and Barns, C. L., 1984, Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation, Science, 225, 1168–1170.PubMedCrossRefGoogle Scholar
  30. 28.
    Kuhl, D. E., E. J. Metter, W. H. Riege, and M. E. Phelps, 1982, Effects of human aging on patterns of local cerebral glucose utilization determined with the [18F]fluorodeoxyglucose method. J. Cerebr. Blood Flow Metab., 2, 163–171.Google Scholar
  31. 29.
    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. Neurol., 34, 939–944.Google Scholar
  32. 30.
    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. Cerebr. Blood Flow Metab., 4, 500–506.Google Scholar
  33. 31.
    Pandya, D. N., and Seltzer, B., 1982, Association areas of the cerebral cortex, Trends Neurosci., 5, 386–390.CrossRefGoogle Scholar
  34. 32.
    Pearson, R. C., Esiri, M. M., Hiorns, R. W., Wikock, G. K., and Powell T. P., 1985, Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer’s disease, Proc. Natl. Acad. Sci., 82, 4531–4534.PubMedCrossRefGoogle Scholar
  35. 33.
    Rapoport, S. I., Horwitz, B., and Duara, R., 1985, PET scanning demonstrates that aging in man is accompanied by loss of integration of regional brain activity, without concurrent reductions in absolute cerebral metabolic rates for glucose, J. Cerebr. Blood Flow Metab., 35 (Suppl. 1), S119–S120.Google Scholar
  36. 34.
    Rapoport, S. I., Horwitz, B., Haxby, J. V., and Grady, C. L., in press, Alzheimer s disease: metabolic uncoupling of associative brain regions, Can. J. Neurological Sci.Google Scholar
  37. 35.
    Rogers, J., and Morrison J. H., 1985, Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer’s disease, J. Neurosci., 5, 2801–2808.PubMedGoogle Scholar
  38. 36.
    Scheibel, A. B., 1978, Structural aspects of the aging brain: spine systems and the dendritic arbor, In: “Aging. Volume 7. Alzheimer’s Disease: Senile Demencia and Related Disorders”, R. Katzman, R. D. Terry, K. L. Bick, eds., Raven Press, New York, pp. 353–373.Google Scholar
  39. 37.
    Schlageter, N. L., Horwitz, B., Creasey, H., Carson, R., Duara, R., Berg, G. W., and Rapoport, S. I., in press, Relation of brain glucose utilization to cortical atrophy and intracranial volume in man, J. Neurol. Neurosurg. Psychiatr.Google Scholar
  40. 38.
    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, 403–420.PubMedCrossRefGoogle Scholar
  41. 39.
    Soncrant, T. T., Horwitz, B., Sato, S., Holloway, H. W., and Rapoport, S. I., 1986, Left-right regional functional interactions are disrupted by corpus callosotomy in the rat, Abstr. Soc. Neurosci., 12, 177.Google Scholar
  42. 40.
    Terry, R. D., Peck, A., DeTeresa R., Schechter, R., and Horoupion, D. S., 1981, Some morphometric aspects of the brain in senile dementia of the Alzheimer type, Ann. Neurol., 10, 184–192.PubMedCrossRefGoogle Scholar
  43. 41.
    Van Hoesen, G. W., 1982, The parahippocampal gyrus. New observations regarding its cortical connections in the monkey, Trends Neurosci., 1, 345–350.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • Stanley I. Rapoport
    • 1
  • Barry Horwitz
    • 1
  • C. L. Grady
    • 1
  • J. V. Haxby
    • 1
  1. 1.Laboratory of Neurosciences National Institute on AgingNational Institutes of HealthBethesdaUSA

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