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Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: A cross-sectional comparison against advanced late-onset and incipient early-onset cases

Journal of Neural Transmission - Parkinson's Disease and Dementia Section

Summary

Global cerebral blood flow and the cerebral metabolic rates of oxygen, CO2, glucose and lactate were studied in 11 patients aged 61–78 years who had been clinically diagnosed as suffering from incipient late-onset dementia of the Alzheimer type (DAT), and in 7 patients aged 66–83 years, in whom advanced late-onset DAT had been diagnosed, using the Kety-Schmidt technique. In incipient late-onset DAT, the predominant abnormality was a 45% reduction in cerebral glucose utilization, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were diminished by only 17% and 18%, respectively. A severe imbalance between oxygen utilization and glucose utilization thus became obvious. In contrast, in advanced stages of late-onset DAT, this imbalance between oxygen and glucose utilization rates in the brain became smaller and smaller, and cerebral blood flow diminished markedly; these biological brain parameters finally all settled down at between 55% and 65% of the corresponding control values. The predominant abnormality in brain glucose utilization in incipient late-onset DAT may be associated with an impairment of its control mechanism(s), which are assumed to be either an influence of brain insulin action, or brain insulin receptor function, or both.

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References

  • Bernsmeier A, Siemons K (1953) Die Messung der Hirndurchblutung mit der Stickoxydul-Methode. Pflügers Arch Ges Physiol 258: 149–162

    Article  Google Scholar 

  • Blass JP, Baker AC, Ko LW, Black RS (1990) Induction of Alzheimer antigens by an uncoupler of oxidative phosphorylation. Arch Neurol 47: 864–869

    PubMed  Google Scholar 

  • Bowen DM, Davison AN (1986) Biochemical studies of nerve cells and energy metabolism in Alzheimer's disease. Br Med Bull 42: 75–80

    PubMed  Google Scholar 

  • Bowen DM, Smith CB, White P, Flack RHA, Carrasco LH, Gedye JL, Davison AN (1977) Chemical pathology of the organic dementias. II. Quantitative estimation of cellular changes in postmortem brains. Brain 100: 427–453

    PubMed  Google Scholar 

  • Bowen DM, White P, Spillane JA, Goodhardt MJ, Curzon G, Iwangoff P, Meier-Ruge W, Davison AN (1979) Accelerated ageing or selective neuronal loss as an important cause of dementia? Lancet i: 11–14

    Google Scholar 

  • Broer Y, Lhiaubet AM, Rosselin G, Rostène W (1987) Etude radioautographique et quantitative des sites des liaison de l'insulin dans le cerveau de rat. Comptes rendus 304: 31–36

    Google Scholar 

  • Butler RN, Dastur DK, Perlin S (1965) Relationships of senile manifestations and chronic brain syndromes to cerebral circulation and metabolism. J Psychiatr Res 3: 229–238

    PubMed  Google Scholar 

  • Dastur DK (1985) Cerebral blood flow and metabolism in normal human aging, pathological aging, and senile dementia. J Cereb Blood Flow Metab 5: 1–9

    PubMed  Google Scholar 

  • de Leon MJ, George AE, Tomanelli J, Christman D, Kluger A, Miller J, Ferris SH, Fowler J, Brodie JD, van Gelder P, Klinger A, Wolf AP (1987) Positron emission tomography studies of normal aging: a replication of PET III and 18-FDG using PET VI and 11-CDG. Neurobiol Aging 8: 319–323

    Article  PubMed  Google Scholar 

  • Farrer LA, Myers RH, Cupples LA, St. George-Hyslop PH, Bird TD, Rossor MN, Mullan MJ, Polinsky R, Nee L, Heston L, van Broeckhoven C, Martin JJ, Crapper-McLachlan D, Growdon JH (1990) Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity. Neurology 40: 395–403

    PubMed  Google Scholar 

  • Frackowiak RS, Pozzilli C, Legg NJ, DuBoulay GH, Marshall J, Lenzi GL, Jones T (1981) Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with oxygen-15 and positron tomography. Brain 104: 753–778

    PubMed  Google Scholar 

  • Freyhan FA, Woodford RB, Kety SS (1951) Cerebral blood flow and metabolism in psychoses of senility. J Nerv Ment Dis 113: 449–456

    PubMed  Google Scholar 

  • Friedland RP, Jagust WJ, Huesman RH, Koss E, Knittel B, Mathis CA, Ober BA, Mazoyer BM, Budinger TF (1989) Regional cerebral glucose transport and utilization in Alzheimer's disease. Neurology 39: 1427–1434

    PubMed  Google Scholar 

  • Frölich L, Eilles C, Ihl R, Maurer K, Lanczik M (1989) State-dependent reductions of regional cerebral blood flow measured by HMPAO-SPECT in dementia of Alzheimer type. Psychiatr Res 29: 347–350

    Google Scholar 

  • Gibson GE, Sheu KFR, Blass JP, Baker A, Carlson KC, Harding B, Perrino P (1988) Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease. Arch Neurol 45: 836–840

    PubMed  Google Scholar 

  • Goate AM, Haynes AR, Owen MJ, Farrall M, James LA, Lai LYC, Mullan MJ, Roques P, Rossor MN, Williamson R, Hardy JA (1989) Predisposing locus for Alzheimer's disease on chromosome 21. Lancet i: 352–355

    Google Scholar 

  • Gottfries CG (1985) Transmitter deficits in Alzheimer's disease. Neurochem Int 7: 565–566

    Article  Google Scholar 

  • Gottfries CG, Adolfsson R, Aquilonius SM, Carlsson A, Eckernäs SA, Nordberg A, Oreland L, Svennerholm L, Widberg A, Winblad B (1983) Biochemical changes in dementia disorders of Alzheimer type (AD/SDAT). Neurobiol Aging 4: 261–271

    Article  PubMed  Google Scholar 

  • Havrankova J, Schmelchel D, Roth J, Brownstein M (1978) Identification of insulin in rat brain. Proc Natl Acad Sci 75: 5737–5741

    PubMed  Google Scholar 

  • Hoyer S (1985) Metabolism of the human brain: the principle and limitation of global measurements. In: Hartmann A, Hoyer S (eds) Cerebral blood flow and metabolism measurement. Springer, Berlin Heidelberg New York, pp 382–390

    Google Scholar 

  • Hoyer S (1986) Senile dementia and Alzheimer's disease. Brain blood flow and metabolism. Prog Neuropsychopharmacol Biol Psychiatry 10: 447–478

    Article  PubMed  Google Scholar 

  • Hoyer S (1988) Glucose and related brain metabolism in dementia of Alzheimer type and its morphological significance. Age 11: 158–166

    Google Scholar 

  • Hoyer S (1990) Brain glucose and energy metabolism during normal aging. Aging 2: 245–258

    PubMed  Google Scholar 

  • Hoyer S, Nitsch R (1989) Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. J Neural Transm 75: 227–232

    Article  PubMed  Google Scholar 

  • Hoyer S, Oesterreich K, Wagner O (1988) Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? J Neurol 235: 143–148

    Article  PubMed  Google Scholar 

  • Iwangoff P, Armbruster R, Enz A, Meier-Ruge W, Sandoz P (1980) Glycolytic enzymes from human autoptic brain cortex: normally aged and demented cases. In: Roberts PJ (ed) Biochemistry of dementia. Wiley, Chichester, pp 258–262

    Google Scholar 

  • Jaspers K (1959) Allgemeine Psychopathologie, 7. Aufl. Springer, Berlin Göttingen Heidelberg, S 146–186

    Google Scholar 

  • Jope R, Blass JP (1976) The regulation of pyruvate dehydrogenase in brain in vivo. J Neurochem 26: 709–714

    PubMed  Google Scholar 

  • Kahn CR (1985) The molecular mechanism of insulin action. Annu Rev Med 36: 429–451

    Article  PubMed  Google Scholar 

  • Kalaria RN, Harik SI (1989) Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer disease. J Neurochem 53: 1083–1088

    PubMed  Google Scholar 

  • Kety SS, Schmidt CF (1948) The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure and normal values. J Clin Invest 27: 476–483

    Google Scholar 

  • Kyriakis JM, Hausman RE, Peterson SW (1987) Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons. Proc Natl Acad Sci USA 84: 7463–7467

    PubMed  Google Scholar 

  • Larsson T, Sjögren T, Jacobsen G (1963) Senile dementia. A clinical, sociomedical and genetic study. Acta Psychiatr Scand [Suppl] 167: 13–259

    Google Scholar 

  • Lassen NA, Klee A (1965) Cerebral blood flow determined by saturation and desaturation with Krypton85. Circ Res 16: 26–32

    PubMed  Google Scholar 

  • Liguri G, Taddei N, Nassi P, Latorraca S, Nediani C, Sorbi S (1990) Changes in Na+, K+-ATPase, Ca2+-ATPase and some soluble enzymes related to energy metabolism in brains of patients with Alzheimer's disease. Neurosci Lett 112: 338–342

    Article  PubMed  Google Scholar 

  • Lying-Tunell U, Lindblad BS, Malmlund HO, Persson B (1981) Cerebral blood flow and metabolic rate of oxygen, glucose, lactate, pyruvate, ketone bodies and amino acids. II. Presenile dementia and normal-pressure hydrocephalus. Acta Neurol Scand 63: 337–350

    PubMed  Google Scholar 

  • Mann DMA, Yates PO, 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: 185–207

    PubMed  Google Scholar 

  • Mellerup ET, Rafaelsen OJ (1969) Brain glycogen after intracisternal insulin injection. J Neurochem 16: 777–781

    PubMed  Google Scholar 

  • Norberg K, Siesjö BK (1976) Oxidative metabolism of the cerebral cortex of the rat in severe insulin-induced hypoglycaemia. J Neurochem 26: 345–352

    PubMed  Google Scholar 

  • Perry EK, Perry RH, Tomlinson BE, Blessed G, Gibson PH (1980) Coenzyme A acetylating enzymes in Alzheimer's disease: possible cholinergic “compartment” of pyruvate dehydrogenase. Neurosci Lett 18: 105–110

    Article  PubMed  Google Scholar 

  • Phillips ME, Coxon RV (1976) Effect of insulin and phenobarbital on uptake of alpha-deoxyglucose by brain slices and hemidiaphragms. J Neurochem 27: 643–645

    PubMed  Google Scholar 

  • Rinaudo MT, Curto M, Bruno R (1985) Effect of insulin on the pyruvate dehydrogenase complex in the rat brain. Ital J Biochem 34: 229–238

    PubMed  Google Scholar 

  • Rossor MN, Iversen LL, Reynolds GP, Mountjoy CQ, Roth M (1984) Neurochemical characteristics of early and late onset types of Alzheimer's disease. Br Med J 288: 961–964

    Google Scholar 

  • Roth M (1986) The association of clinical and neurological findings and its bearing on the classification and aetiology of Alzheimer's disease. Br Med Bull 42: 42–50

    PubMed  Google Scholar 

  • Schneider K (1958) Klinische Psychopathologie, 5. Aufl. Thieme, Stuttgart, S 63

    Google Scholar 

  • Shaw TG, Mortel KF, Meyer JS, Rogers RL, Hardenberg J, Cutaia MM (1984) Cerebral blood flow changes in benign aging and cerebrovascular disease. Neurology (Cleveland) 34: 855–862

    Google Scholar 

  • Sims NS, Blass JP, Murphy C, Bowen DM, Neary D (1987b) Phosphofructokinase activity in the brain in Alzheimer's disease. Ann Neurol 21: 509–510

    Article  PubMed  Google Scholar 

  • Sims NR, Bowen DM, Neary D, Davison AN (1983) Metabolic processes in Alzheimer's disease: adenine nucleotide content and production of14CO2 from (U−14C) glucose in vitro in human neocortex. J Neurochem 41: 1329–1334

    PubMed  Google Scholar 

  • Sims NR, Finegan JM, Blass JP, Bowen DM, Neary D (1987a) Mitochondrial function in brain tissue in primary degenerative dementia. Brain Res 436: 30–38

    Article  PubMed  Google Scholar 

  • Sorbi S, Bird ED, Blass JP (1983) Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13: 72–78

    Article  PubMed  Google Scholar 

  • Sumpter PQ, Mann DMA, Davies CA, Yates PO, Snowdon JS, Neary D (1986) An ultrastructural analysis of the effects of accumulation of neurofibrillary tangle in pyramidal neurons of the cerebral cortex in Alzheimer's disease. Neuropathol Appl Neurobiol 12: 305–319

    PubMed  Google Scholar 

  • Wagner O, Oesterreich K, Hoyer S (1985) Validity of the ischemic score in degenerative and vascular dementia and depression in old age. Arch Gerontol Geriatr 4: 333–345

    Article  PubMed  Google Scholar 

  • Weinhardt F, Quadbeck G, Hoyer S (1972) Quantitative Bestimmung von Blutgasvolumina mit Hilfe der Gaschromatographie. Z Prakt Anaesth 6: 337–347

    Google Scholar 

  • Werther GA, Hogg A, Oldfield BJ, McKinley MJ, Figdor R, Allen AM, Mendelsohn FAO (1987) Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry. Endocrinology 121: 1562–1570

    PubMed  Google Scholar 

  • Young WS (1986) Periventricular hypothalamie cells in the rat brain contain insulin mRNA. Neuropeptides 8: 93–97

    Article  PubMed  Google Scholar 

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Hoyer, S., Nitsch, R. & Oesterreich, K. Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: A cross-sectional comparison against advanced late-onset and incipient early-onset cases. J Neural Transm Gen Sect 3, 1–14 (1991). https://doi.org/10.1007/BF02251132

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  • DOI: https://doi.org/10.1007/BF02251132

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