PET scanning for the detection of Alzheimer’s disease

  • W.-D. Heiss
  • B. Szelies
  • R. Adams
  • J. Kessler
  • G. Pawlik
  • K. Herholz
Part of the New Vistas in Drug Research book series (DRUG RESEARCH, volume 1)


At present, PET is the only technology affording the quantitative, three-dimensional imaging of various aspects of brain function. Since function and metabolism are coupled, and since glucose is the dominant substrate of the brain’s energy metabolism, studies of glucose metabolism by PET of 2(18F)-fluoro-2-deoxy-D-glucose (FDG) are widely applied to the investigation of the participation of various brain systems in simple or complex stimulations and tasks. In focal or diffuse disorders of the brain, functional impairment of affected or inactivated brain regions is a reproducible finding.

While glucose metabolism slightly decreases with age to a regionally different degree, in most types of dementia severe changes in glucose metabolism are observed. Degenerative dementia of the Alzheimer type is characterized by a metabolic disturbance most prominent in the parieto-occipitotemporal association cortex and later in the frontal lobe, while primary cortical areas, basal ganglia, thalamus, brainstem and cerebellum are not affected. Thanks to this typical pattern Alzheimer’s disease can be differentiated from other dementia syndromes, such as Pick’s disease (with the metabolic depression mostly prominent in the frontal and temporal lobe), multi-infarct dementia (with multiple focal metabolic defects), Huntington’s chorea (with metabolic disturbances in the neostriatum) and other diseases leading to cognitive impairment with more or less typical metabolic patterns. A ratio calculated form CMRGl of affected (temporo-parieto-occipital and frontal association cortex) and non-affected brain regions (primary cortical areas, brainstem, cerebellum) enabled us to separate clearly AD patients from agematched controls and to discriminate those patients suffering from cognitive impairment of other origin in 82% of the cases. The discrimination power can be further improved by specific activation studies. In demented patients PET can also be used to assess the effects of treatment on disturbed metabolism. Such studies demonstrated an equalization of metabolic heterogeneities in patients responding to muscarinic cholinergic agonists, as well as a diffuse increase of metabolism during treatment with piracetam and phosphatidylserine. The therapeutic relevance of such metabolic effects, however, remains to be proved in controlled clinical trials.


Alzheimer Type Cereb Blood Flow Cerebral Glucose Metabolism Dementia Syndrome Degenerative Dementia 
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  1. Alavi A, Fazekas F, Chawluk J, Zimmerman R (1987) Magnetic resonance imaging of the brain in normal aging and dementia. In: Meyer JS, Lechner H, Reivich M, Ott BO (eds) Cerebral vascular disease 6. Excerpta Medica, Amsterdam New York Oxford, pp 191–195Google Scholar
  2. American Psychiatric Association (1980) Diagnostic and statistical manual of mental disorders, 3rd edition ( DSM-III ). Washington DC, pp 124–126Google Scholar
  3. Baxter LR, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE, (1987) Local cerebral glucose metabolic rates in obsessive-compulsive disorder — a comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry 44: 211–218PubMedCrossRefGoogle Scholar
  4. Coyle JT, Price DL, Delong MR (1983) Alzheimer’s disease: a disorder of cortical cholinergic innervation. Science 219: 1184–1190PubMedCrossRefGoogle Scholar
  5. Davies P, Maloney AJF (1976) Selective loss of control cholinergic neurons in Alzheimer’s disease. Lancet ii: 1403CrossRefGoogle Scholar
  6. Davis KL, Mohs RC, Tinklenberg JR, Pfefferbaum A, Hollister LE, Kopell BS (1978) Physostigmine: improvement of long-term memory processes in normal humans. Science 201: 272–274PubMedCrossRefGoogle Scholar
  7. DeLeon MJ, Ferris SH, George AE, Reisberg B, Christman DR, Kricheff II, Wolf AP (1983) Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer’s disease. J Cereb Blood Flow Metab 3: 391–394CrossRefGoogle Scholar
  8. Duara R, Grady C, Haxby J, Sundaram M, Cutler NR, Heston L, Moore A, Rapoport SI (1986) Positron emission tomography in Alzheimer’s disease. Neurology 36: 879–887PubMedGoogle Scholar
  9. Ferris SH, Reisberg B, Crook T, Friedman E, Schneck K, Mir P, Sherman KA, Corwin J, Gershon S, Bartus RT (1982) Pharmacologic treatment of senile dementia: choline, L-dopa, piracetam, and choline plus piracetam. Aging 19: 475–481Google Scholar
  10. 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: 961–965PubMedGoogle Scholar
  11. Frackowiak RSJ, Pozzilli C, Legg NJ, Du Boulay GM, 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: 753–778PubMedCrossRefGoogle Scholar
  12. Friedland RP, Budinger TF, Ganz E, Yano Y, Mathis CA, Koss B, Ober BA, Huesman RH, Derenzo SE (1983) Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with (18F)fluorodeoxyglucose. J Comput Assist Tomogr 7: 590–598PubMedCrossRefGoogle Scholar
  13. Gibbs JM, Frackowiak RSJ, Legg NJ (1986) Regional cerebral blood flow and oxygen metabolism in dementia due to vascular disease. Gerontology 32 [Suppl 1]: 84–88PubMedCrossRefGoogle Scholar
  14. Hachinski VC, Iliff LD, Zilkha E, Du Boulay GH, Mc Allister VL, Marshall I, Ross Russell RW, Symon L (1975) Cerebral blood flow in dementia. Arch Neurol 32: 632–637PubMedCrossRefGoogle Scholar
  15. Hayden MR, Hewitt J, Stoessl AJ, Clark C, Ammann W, Martin WRW (1987) The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington’s disease. Neurology 37: 1441–1447PubMedGoogle Scholar
  16. Heiss WD, Pawlik G, Herholz K, Wagner R, Göldner H, Wienhard K (1984) Regional kinetic constants and CMRGIu in normal human volunteers determined by dynamic positron emission tomography of (18F)-2-fluoro2-deoxy-D-glucose. J Cereb Blood Flow Metab 4: 212–223PubMedCrossRefGoogle Scholar
  17. Heiss WD, Herholz K, Böcher-Schwarz HG, Pawlik G, Wienhard K, Stein-brich W, Friedmann Cr (1986) PET, CT, and MR imaging in cerebrovascular disease. J Comput Assist Tomogr 10: 903–911PubMedCrossRefGoogle Scholar
  18. Heiss WD, Hebold I, Klinkhammer P, Ziffling P, Szelies B, Pawlik G, Herrholz K (1988) Effect of piracetam on cerebral glucose metabolism in Alzheimer’s disease as measured by PET. J Cereb Blood Flow Metab 8: 613–617PubMedCrossRefGoogle Scholar
  19. Hollander E, Mohs RC, Davis KL (1986) Cholinergie approaches to the treatment of Alzheimer’s disease. Br Med Bull 42: 97–100PubMedGoogle Scholar
  20. Kamo H, McGeer PL, Harrop R, McGeer EG, Calne DB, Martin WRW, Pate BD (1987) Positron emission tomography and histopathology in Pick’s disease. Neurology 37: 439–445PubMedGoogle Scholar
  21. Kessler J, Adams R, Herholz K, Szelies B, Heiss WD (1989) Impaired metabolic activation (FDG-PET) in patients with Alzheimer’s disease under stimulation by continuous recognition. In: Aging of the brain and dementia: ten years later. Conf. World Federation Neurology Florenz, May 31—June 3, 1989Google Scholar
  22. Kuhl DE, Metter EJ, Riege WH, Hawkins RA, Mazziotta JC, Phelps ME, Kling AS (1983) Local cerebral glucose utilization in elderly patients with depression, multiple infarct dementia, and Alzheimer’s disease. J Cereb Blood Flow Metab 3 [Suppl 1]: S 494–S 495Google Scholar
  23. Kuhl DE, Metter EJ, Riege WH, Markham CH (1984) Patterns of cerebral glucose utilization in Parkinson’s disease and Huntington’s disease. Ann Neurol 15 [Suppl]: S 119–S 125CrossRefGoogle Scholar
  24. Kuhl DR, Metter EJ, Benson DF, Ashford JW, Riege WH, Fujikawa DG, Markham CH, Mazziotta JC, Maltese A, Dorsey DA (1985) Similarities of cerebral glucose metabolism in Alzheimer’s and Parkinsonian dementia. J Cereb Blood Flow Metab 5 [Suppl 1]: S 169–S 170Google Scholar
  25. Kurz A, Rüster P, Romero B, Zimmer R (1986) Cholinerge Behandlungsstrategien bei der Alzheimer’schen Krankheit. Nervenarzt 57: 558–569PubMedGoogle Scholar
  26. Mazziotta JC, Phelps ME, Carson RE, Kuhl DE (1982) Tomographic mapping of human cerebral metabolism: sensory deprivation. Ann Neurol 12: 435 444Google Scholar
  27. Mazziotta JC, Phelps ME, Pahl J J, Huang S-G, Baxter LR, Riege WH, Hoffman JM, Kuhl DE, Lanto AB (1987) Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington’s disease. N Engl J Med 316: 357–362PubMedCrossRefGoogle Scholar
  28. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease. Neurology 34: 939–944PubMedGoogle Scholar
  29. Nahmias C, Garnett ES, Firnau G, Lang A (1985) Striatal dopamine distri- bution in Parkinsonian patients during life. J Neurol Sci 69: 223–230PubMedCrossRefGoogle Scholar
  30. Rossor MN, Emson PC, Mountjoy CQ, Roth M, Iversen LL (1982) Neurotransmitters of the cerebral cortex in senile dementia of Alzheimer type. Exp Brain Res [Suppl 5]: 153–157PubMedCrossRefGoogle Scholar
  31. Smith RC, Vroulis G, Johnson R, Morgan R (1984) Pharmacologic treatment of Alzheimer’s type dementia: new approaches. Psychopharmacol Bull 20: 542–545PubMedGoogle Scholar
  32. Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A (1986) Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer-type. N Engl J Med 315: 1241–1245PubMedCrossRefGoogle Scholar
  33. Szelies B, Karenberg A (1986) Störungen des Glukosestoffwechsels bei Pick’scher Erkrankung. Fortschr Neurol Psychiat 54: 393–397PubMedCrossRefGoogle Scholar
  34. Szelies B, Herholz K, Pawlik G, Beil C, Wienhar K, Heiss WD (1986) Zerebraler Glukosestoffwechsel bei präseniler Demenz vom Alzheimer-Typ — Verlaufskontrolle unter Therapie mit muskarinergem Cholinagonisten. Fortschr Neurol Psychiat 54: 364–373PubMedCrossRefGoogle Scholar
  35. Szelies B, Wullen T, Adams R, Grond M, Karbe H, Herholz K (1989) Comparison between cerebral glucose metabolism and late evoked potentials in patients with Alzheimer’s disease. J Neural Transm (P-D Sect) 1: 141CrossRefGoogle Scholar
  36. Terry RD, Peck A, De Teresa R, Schechter R, Horoupian DS (1981) Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol 10: 184–192PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1990

Authors and Affiliations

  • W.-D. Heiss
    • 1
  • B. Szelies
    • 1
  • R. Adams
    • 1
  • J. Kessler
    • 1
  • G. Pawlik
    • 1
  • K. Herholz
    • 1
  1. 1.Max-Planck-Institut für neurologische Forschung und Universitätsklinik für NeurologieKöln (Lindenthal)Federal Republic of Germany

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