Summary
Global cerebral blood flow, oxidative brain metabolism, and the cerebral arteriovenous differences of amino acids and ammonia were studied in 20 clinically diagnosed patients with early-onset dementia of Alzheimer type (DAT). Eleven healthy age-matched subjects and 15 healthy young volunteers served as controls. The most prominent abnormality in patients with early-onset DAT was a 44% reduction in the cerebral metabolic rate of glucose and a fourfold increase of lactate production, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were found not to be altered. The cerebral amino-N balance substantially changed in patients with early-onset DAT, showing a massive loss of amino acids and ammonia from the brain, which was indicative of excess protein catabolism due to cell degeneration in the acutely diseased brain. The abnormality found in glucose metabolism may suggest a perturbed control of glycolytic breakdown of glucose and its first oxidation step at the pyruvate dehydrogenase complex level, this thus being of pivotal significance in early-onset DAT.
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Alzheimer A (1907) Über eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatr 64:146–148
Alzheimer A (1911) Über eigenartige Krankheitsfälle des späteren Alters. Z Ges Neurol Psychiatr 4:356–385
Barkulis SS, Geiger A, Kawakita Y, Aguilar V (1960) A study of the incorporation of 14C derived from glucose into free amino acids of the brain cortex. J Neurochem 5:339–348
Benson DF, Kuhl DE, Hawkins RA, Phelps ME, Cummings JL, Tsai SY (1983) The fluorodeoxy-glucose18 F scan in Alzheimer's disease and multi infarct dementia. Arch Neurol 40:711–714
Bernsmeier A, Siemons K (1953) Die Messung der Hirndurchblutung mit der Stickoxydul-Methode. Pflügers Arch Gesamte Physiol 258:149–162
Bowen DM, Davison AN (1986) Biochemical studies of nerve cells and energy metabolism in Alzheimer's disease. Br Med Bull 42:75–80
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 post-mortem brains. Brain 100:427–453
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
Chase TN, Foster NL, Defio P, Di Chiro G, Brooks R, Patronas NJ (1983) Alzheimer's disease: local cerebral metabolism studies using the 18F-fluorodeoxy-positron emission tomography technique. In: Samuel D, Algeri S, Gershon S, Grimm VE, Toffano G (eds) Aging of the brain (Aging, vol. 22). Raven. New York, pp 143–154
Cutler NR, Haxby JV, Duara R, Grady CL, Kay AD, Kessler RM, Sundaram M, Rapoport SI (1985) Clinical history, brain metabolism, and neuropsychological function in Alzheimer's disease. Ann Neurol 18:298–309
Dekoninck WJ, Jaquy J, Joquet P, Noel G (1977) Cerebral blood flow and metabolism in senile dementia. In: Meyer JS, Lechner H, Reivich M (eds) Cerebral vascular disease. Excerpta Medica, Amsterdam, pp 29–32
Foster NL, Chase TN, Fedio P, Patronas NJ, Brooks RA, Di Chiro G (1983) Alzheimer's disease: focal cortical changes shown by positron emission tomography. Neurology 33:961–965
Foster NL, Chase TN, Mansi L, Brooks R, Fedio P, Patronas NJ, Di Chiro G (1984) Cortical abnormalities in Alzheimer's disease. Ann Neurol 16:649–654
Frackowiak RSJ, 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
Freyhan FA, Woodford RB, Kety SS (1951) Cerebral blood flow and metabolism in psychoses of senility. J Nerv Ment Dis 113:449–456
Geiger A, Kawakita Y, Barkulis SS (1960) Major pathways of glucose utilization in the brain in brain perfusion experiments in vivo and in situ. J Neurochem 5:323–338
Gottfries CG (1985) Transmitter deficits in Alzheimer's disease. Neurochem Int 7:565–566
Gottfries CG, Adolfsson R, Aquilonius SM, Carlsson A, Eckernäs SA, Nordberg A, Oreland L, Svennerholm L, Wiberg A, Winblad B (1983) Biochemical changes in dementia disorders of Alzheimer type (AD/SDAT). Neurobiol Aging 4:261–271
Greenamyre JT, Penney JB, D'Amato CJ, Young AB (1987) Dementia of the Alzheimer's type: changes in hippocampal L- (3H) glutamate binding. J Neurochem 48:543–551
Gustafson L, Hagberg B (1975) Emotional behavior, personality changes and cognitive reduction in presenile dementia: related to regional cerebral blood flow. Acta Psychiatr Scand [Suppl] 257:38–71
Gustafson L, Risberg J (1974) Regional cerebral blood flow related to psychiatric symptoms in dementia with onset in the presenile period. Acta Psychiatr Scand 50:516–538
Gustafson L, Brun A, Ingvar DH (1977) Presenile dementia: clinical symptoms, pathoanatomical findings and cerebral blood flow. In: Meyer JS, Lechner H, Reivich M (eds) Cerebral vascular disease. Excerpta Medica, Amsterdam, pp 5–9
Hachinski VC, Iliff LD, Zilkha E, DuBoulay GH, McAllister VL, Marshall J, Ross-Russell RW, Symon L (1975) Cerebral blood flow in dementia. Arch Neurol 32:632–637
Haxby JV, Duara R, Grady CL, Culter NR, Rapoport SI (1985) Relations between neuropsychological and cerebral asymmetrics in early Alzheimer's disease. J Cereb Blood Flow Metabol 5:193–200
Hoyer S (1970) Der Aminosäurenstoffwechsel des normalen menschlichen Gehirns. Klin Wochenschr 48:1239–1243
Hoyer S (1978) Blood flow and oxidative metabolism of the brain in different phases of dementia. In: Katzman R, Terry RD, Bick KL (eds) Alzheimer's disease senile dementia and related disorders (Aging, vol 7). Raven, New York, pp 219–226
Hoyer S (1980) Factors influencing cerebral blood flow, CMR-oxygen and CMR-glucose in dementia patients. In: Roberts PJ (ed) Biochemistry of dementia. Wiley, Chichester, pp 252–257
Hoyer S (1982) The abnormally aged brain. Its blood flow and oxidative metabolism. A review — part II. Arch Gerontol Geriatr 1:195–207
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
Hoyer S (1985) The effect of age on glucose and energy metabolism in brain cortex of rats. Arch Gerontol Geriatr 4:193–203
Hoyer S (1986) Senile dementia and Alzheimer's diseases. Brain blood flow and metabolism. Prog Neurosychopharmacol Biol Psychiatry 10:447–478
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
Jaspers K (1959) Allgemeine Psychopathologie, 7th edn. Springer, Berlin Göttingen Heidelberg, pp 146–186
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
Ladurner G, Ott EO, Perry PJ, Stix P, Schreyer H, Wiedner F, Lechner H (1977) Bilateral measurement of regional cerebral blood flow in dementia. In: Meyer JS, Lechner H, Reivich M (eds) Cerebral vascular disease. Excerpta Medica, Amsterdam, pp 10–13
Larsson T, Sjögren T, Jacobsen G (1963) Senile dementia. A clinical, sociomedical and genetic study. Acta Psychiatr Scand [Suppl] 167:13–259
Lassen NA, Klee A (1965) Cerebral blood flow determined by saturation and desaturation with Krypton85. Circ Res 16:26–32
Lassen NA, Munck O, Toffey ER (1957) Mental function and cerebral oxygen consumption in organic dementia. Arch Neurol Psychiatry 77:126–133
Lassen NA, Feinberg I, Lane MH (1960) Bilateral studies of cerebral oxygen uptake in young and aged normal subjects and in patients with organic dementia. J Clin Invest 39:491–500
Lyning-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
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
Moore S, Stein WH (1954) Procedures for the chromatographic determination of amino acids on four per cent cross-linked sulfonated polystyene resins. J Biol Chem 211:893–906
Moore S, Stein WH (1954) A modified ninhydrin reagent for the photometric determination of amino acids and related compounds. J Biol Chem 211:907–913
O'Brien MD (1972) Somes aspects of cerebral blood flow in dementia. In: Meyer JS, Reivich M, Lechner H, Eiohhorn O (eds) Research on the cerebral circulation. Thomas, Springfield, pp 287–290
O'Brien MD, Mallett BL (1970) Cerebral cortex perfusion rates in dementia. J Neurol Neurosurg Psychiatry 33:497–500
Obrist WD, Chivian E, Cronquist S, Ingvar DH (1970) Regional cerebral blood flow in senile and presenile dementia. Neurology 20:315–322
Perry EK, Perry RH, Tomlinson BE, Blessed G, Gibson PH (1980) Coenzyme-A acetylating enzymes in Alzheimer disease: possible cholinergic “compartment” of pyruvate dehydrogenase. Neurosci Lett 18:105–110
Rogers RL, Meyer JS, Mortel KF, Mahurin RK, Judd BW (1986) Decreased cerebral blood flow precedes multi-infarct dementia, but follows senile dementia of Alzheimer type. Neurology 36:1–6
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
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
Sacks W (1965) Cerebral metabolism of doubly labeled glucose in humans in vivo. J Appl Physiol 20:117–130
Schneider K (1958) Klinische Psychopathologie, 5th edn. Thieme, Stuttgart, p 63
Sims NR, Bowen DM, Smith CCT, Flack RHA, Davison AN, Snowdon JS, Neary D (1980) Glucose metabolism and acetylcholine synthesis in relation to neuronal activity in Alzheimer's disease. Lancet I:333–336
Sims NR, Bowen DM, Davison AN (1981) (14C) Acetylcholine synthesis and (14C) carbon dioxide production from (U-14C) glucose by tissue prisms from human neocortex. Biochem J 196:867–876
Sims NR, Bowen DM, Allen SJ, Smith CCT, Neary D, Thomas DJ, Davison AN (1983) Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 40:503–509
Sims NR, Bowen DM, Neary D, Davison AN (1983) Metabolic processes in Alzheimer's disease: adenine nucleotide content and production of 14CO2 from (U-14C) glucose in vitro in human neocortex. J Neurochem 41:1329–1334
Sims NR, Finegan JM, Blass JP (1985) Altered glucose metabolism in fibroblasts from patients with Alzheimer disease. N Engl J Med 313:638–639
Smith CB, Goochee C, Rapoport SI, Sokoloff L (1980) Effects of ageing on local rates of cerebral glucose utilization in the rat. Brain 103:351–356
Sorbi S, Bird ED, Blass JP (1983) Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13:72–78
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
Tachibana H, Meyer JS, Kitagawa Y, Rogers RL, Okayasu H, Mortel KF (1984) Effects of aging on cerebral blood flow in dementia. J Am Geriatr Soc 32:114–120
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
Weinhardt F, Quadbeck G, Hoyer S (1972) Quantitative Bestimmung von Blutgasvolumina mit Hilfe der Gaschromatographie. Z Prakt Anaesth 6:337–347
Wong KL, Tyce GM (1983) Glucose and amino acid metabolism in rat brain during sustained hypoglycemia. Neurochem Res 8:401–415
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Hoyer, S., Oesterreich, K. & Wagner, O. Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type?. J Neurol 235, 143–148 (1988). https://doi.org/10.1007/BF00314304
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DOI: https://doi.org/10.1007/BF00314304