Positron emission tomography for diagnosis of Alzheimer’s disease and vascular dementia

  • R. Mielke
  • W.-D. Heiss
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 53)


In mild or atypical cases of Alzheimer’s disease (AD) the differential diagnosis to other dementing diseases, such as vascular dementia (VD), may pose a difficult problem. Beside computed tomography (CT) and magnetic resonance imaging (MRI), functional neuroimaging by positron emission tomography (PET) support the clinical diagnosis by visualizing cerebral function. PET of 18F-2-fluoro-2-deoxy-D-glucose (FDG) for measurement of regional cerebral glucose metabolism (rCMRG1) has shown a typical metabolic pattern in patients with probable AD: hypometabolism in temporoparietal and frontal association areas, but relative recessing of primary cortical areas, basal ganglia and cerebellum. In VD a different pattern is seen. It consists of scattered areas with reduction of rCMRGl typically extending over cortical and subcortical structures. Severity of dementia is correlated with rCMRGl reduction in the temporoparietal association cortex, irrespective of the cause of dementia. Also the total volume of hypometabolic regions is related to severity of dementia but did not differ between AD and VD, even in patients with small lacunar infarction. This indicates that the total volume of functional tissue loss is more important, since it also includes the effects of incompletely infarcted tissue and morphologically intact but deafferented cortex. The characteristic metabolic pattern has a high diagnostic accuracy for the discrimination between probable AD, normals and VD, even in patients with mild cognitive impairment. Under clinical and therapeutic aspects the analysis of longitudinal changes of rCMRGl has shown that neuropsychological and metabolic changes are closely related in both, AD and VD.


Vascular Dementia Metabolic Ratio Vascular Dementia Patient Regional Cerebral Glucose Metabolism HMPAO SPECT 
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  1. American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd rev. edn. American Psychiatric Association, Washington DCGoogle Scholar
  2. Benson DF, Kuhl DE, Hawkins RA, Phelps ME, Cummings JL, Tsai SY (1983) The fluordeoxyglucose 18F scan in Alzheimer’s disease and multi-infarct dementia. Arch Neurol 40: 711–714PubMedCrossRefGoogle Scholar
  3. Breitner JCS, Silverman JM, Mohs RC, Davis KL (1988) Familial aggregation in Alzheimer’s disease: comparison od risk among relatives of early-and late-onset cases, and among male and female relatives in successive generations. Neurology 38: 207–212PubMedCrossRefGoogle Scholar
  4. Chase TN, Foster NL, Mansi L (1983) Alzheimer’s disease and the parietal lobe. Lancet ii: 225CrossRefGoogle Scholar
  5. Chui HC, Victoroff JI, Margolin D, Jagust W, Shankle R, Katzman R (1992) Criteria for the diagnosis of ischemic vascular dementia proposed by the state of California Alzheimer’s disease diagnostic and treatment centers. Neurology 42: 473–480PubMedCrossRefGoogle Scholar
  6. DeCarli C, Kaye JA, Horwitz B, Rapoport SI (1990) Critical analysis of the use of computer assisted transverse axial tomography to study human brain in aging and dementia of the Alzheimer type. Neurology 40: 872–883CrossRefGoogle Scholar
  7. Duara R, Grady C, Haxby J, Sundaram M, Cutler NR, Heston L, Moore A, Schlageter N, Larson S, Rapoport SI (1986) Positron emmission tomography in Alzheimer’s disease. Neurology 36: 879–887PubMedCrossRefGoogle Scholar
  8. Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental State: a practical method for grading the cognitive status of patients for the clinician. J Psychiatr Res 12: 189–198PubMedCrossRefGoogle Scholar
  9. Foster NL, Chase TN, Fedio P, Patronas NJ, Brooks RA, DiChiro G (1983) Alzheimer’s disease: focal cortical changes shown by positron emission tomography. Neurology (Cleveland) 33: 961–965CrossRefGoogle Scholar
  10. Frackowiak RSJ, Pozzilli C, Legg NJ, du Boulay GH, Marshall J, Lenzi GL, Jones T (1981) Regional cerebral oxygen supply and utilization in dementia. Brain 104: 753–778PubMedCrossRefGoogle Scholar
  11. 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’s type: positron emission tomography with (18F)fluordeoxyglucose. J Comput Assist Tomogr 7: 5590–598CrossRefGoogle Scholar
  12. Gemmel HG, Sharp PF, Besson JAO, Crawford JR, Ebmeier KP, Davidson J, Smith FW (1987) Differential diagnosis in dementia using cerebral blood flow agent TC-99m HM-PAO: a SPECT study. J Comput Assist Tomogr 11: 398–402CrossRefGoogle Scholar
  13. Gemmell HG, Sharp PF, Besson JAO, Ebmeier KP, Smith FW (1988) A comparison of TC-99m HM-PAO and 1–123 IMP cerebral SPECT images in Alzheimer’s disease and multi-infarct dementia. Eur J Nucl Med 14: 463–466PubMedCrossRefGoogle Scholar
  14. Gemmel HG, Evans NTS, Besson JAO, Roeda D, Davidson J, Dodd MG, Sharp PF, Smith FW, Crawford JR, Newton RH, Kulkarni V, Mallard JR (1990) Regional cerebral blood flow imaging: a quantitative comparison of Technetium-99m-HMPAO SPECT with C15O2 PET. J Nucl Med 31: 1595–1600Google Scholar
  15. Gibbs JM, Frackowiak RSJ, Legg NJ (1986) Regional cerebral blood flow and oxygen metabolism in dementia due to vascular disease. Gerontology 32 [Suppl 1]: 84–86PubMedCrossRefGoogle Scholar
  16. Grady CL, Haxby JV, Horwitz B, Berg G, Rapoport SI (1987) Neuropsychological and cerebral metabolic function in early vs late onset dementia of the Alzheimer type. Neuropsychologia 25: 807–816PubMedCrossRefGoogle Scholar
  17. Grady CL, Haxby JV, Horwitz B, Sundaram M, Berg G, Schapiro M, Friedland RP, Rapoport SI (1988) Longitudinal study of the early neuropsychological and cerebral changes in dementia of the Alzheimer type. J Clin Exp Neuropsychol 10: 576–596PubMedCrossRefGoogle Scholar
  18. Hachinski VC, Iliff LD, Zilhka E, DuBoulay GH, McAllister VL, Marshall J, Russell RWR, Symon L (1975) Cerebral blood flow in dementia. Arch Neurol 32: 632–637PubMedCrossRefGoogle Scholar
  19. Haxby JV, Grady CL, Duara R, Schlageter N, Berg G, Rapoport SI (1986) Neocortical abnormalities precede nonmemory cognitive defects in early Alzheimer’s type dementia. Arch Neurol 43: 882–885PubMedCrossRefGoogle Scholar
  20. Haxby JV, Grady CL, Koss E, Horwitz B, Heston L, Schapiro M, Friedland RP, Rapoport SI (1990) Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological patterns in early dementia of the Alzheimer type. Arch Neurol 47: 753–760PubMedCrossRefGoogle Scholar
  21. Heiss WD, Ilsen HW, Wagner R, Pawlik G, Wienhard K, Eriksson L (1983) Remote functional depression of glucose metabolism in stroke and its alteration by activating drugs. In: Heiss WD, Phelps ME (eds) Positron emission tomography of the brain. Springer, Berlin Heidelberg New York Tokyo, pp 162–168CrossRefGoogle Scholar
  22. Heiss WD, Hebold I, Klinkhammer P, Ziffling P, Szelies B, Pawlik G, Herholz K (1988) Effect of piracetam on cerebral glucose metabolism in Alzheimer’s disease as measured by positron emission tomography. J Cereb Blood Flow Metab 8: 613–617PubMedCrossRefGoogle Scholar
  23. Heiss WD, Kessler J, Mielke R, Szelies B, Herholz K (1994) Long-term effects of Phosphatidylserine, Pyritinol, and cognitive training in Alzheimer’s disease. A neuropsychological, EEG, and PET investigation. Dementia 5: 88–98Google Scholar
  24. Herholz K, Adams R, Kessler J, Szelies B, Grond M, Heiss WD (1990) Criteria for the diagnosis of Alzheimer’s disease with positron emission tomography. Dementia 1: 156–164Google Scholar
  25. Heston LL, Mastri AR, Anderson VE, White J (1981) Dementia of the Alzheimer type. Clinical genetics, natural history and associated conditions. Arch Gen Psychiatry 38: 1085–1090PubMedCrossRefGoogle Scholar
  26. Jagust WJ, Friedland RP, Budinger TF, Koss E, Ober B (1988) Longitudinal studies of regional cerebral metabolism in Alzheimer’s disease. Neurology 38: 909–912PubMedCrossRefGoogle Scholar
  27. Kamo H, McGeer P, Harrop R, McGeer E, Calne D, Martin W, Pate B (1987) Positron emission tomography and histopathology in Pick’s disease. Neurology 37: 439PubMedCrossRefGoogle Scholar
  28. Kase CS (1991) Epidemiology of multi-infarct dementia. Alz Dis Assoc Disord 5: 71–76CrossRefGoogle Scholar
  29. Kennedy AM, Newman S, Clegg F, Tyrrell P, Warrington EK, Roques P, Hardy J, Rossor MN, Frackowiak RSJ (1992) Imaging in dementia: longitudinal studies using positron emission tomography. Neurobiol Aging 13: S13CrossRefGoogle Scholar
  30. Kessler J, Herholz K, Heiss WD (1991) Impaired metabolic activation in Alzheimer’s disease: a PET study during continous visual recognition. Neuropsychologia 29: 229–243PubMedCrossRefGoogle Scholar
  31. Klinkhammer P, Szelies B, Heiss WD (1990) Effect of phosphatidylserine on cerebral glucose metabolism in Alzheimer’s disease. Dementia 1: 197–201Google Scholar
  32. Kraepelin E (1910) Psychiatrie, ein Lehrbuch für Studierende und Ärzte, 8th edn, vol II/1. Barth, LeipzigGoogle Scholar
  33. Kuhl DE, Phelps ME, Kowell AP, Metter EJ, Selin C, Winter J (1980) Effects of stroke on local cerebral metabolism and perfusion: mapping by emission computed tomography of 18FDG and 13NH3. Ann Neurol 8: 47–60PubMedCrossRefGoogle Scholar
  34. Kuhl D, Phelps M, Markham C (1982) Cerebral metabolism and atrophy in Huntington’s disease determined by 18-FDG and computed tomographic scan. Ann Neurol 12: 425–434PubMedCrossRefGoogle Scholar
  35. Kuhl DE, Metter EJ, Riege WH, Hawkings RA, Mazziotta JC, Phelps DE, 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: S494–S495Google Scholar
  36. Kuhl D, Metter E, Benson F, Ashford JW, Riege WH, Fujikawa DG, Markham CH, Mazziotta JC, Maltese A, Dorsey DA (1985) Similarities of cerebral glucose metabolism in Alzheimer’s and Parkinson’s dementia. J Cereb Blood Flow Metab 5: 169–170Google Scholar
  37. Kuwert T, Lange HW, Langen KJ, Herzog H, Aulich A, Feinendegen LE (1990) Cortical and subcortical glucose consumption measured by PET in patients with Huntington’s disease. Brain 113: 1405–1423PubMedCrossRefGoogle Scholar
  38. Mann DMA, Yates PO, Marcyniuk B (1984) Alzheimer’s presenile dementia, senile dementia of Alzheimer type and Down’s syndrome in middle age from an age related continuum of pathological changes. Neuropathol Appl Neurobiol 10: 185–207PubMedCrossRefGoogle Scholar
  39. McGeer PL, Kamo H, Harrop R, Li DK, Tuokko H, McGeer EG, Adam MJ, Ammann W, Beattie BL, Calne DB (1986) Positron emission tomography in patients with clinical diagnosed Alzheimer’s disease. Can Med Assoc J 134: 597–607Google Scholar
  40. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (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 19: 939–944CrossRefGoogle Scholar
  41. Messa C, Perani D, Lucignani G, Zenorini A, Zito F, Rizzo G, Grassi F, Del Sole A, Franceschi M, Gilardi MC, Fazio F (1994) High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer’s disease: comparison with fluorine-18-FDG PET. J Nucl Med 35: 210–216PubMedGoogle Scholar
  42. Mielke M, Ghaemi J, Kessler B, Kittner B, Szelies B, Herholz K, Heiss WD (1998) Propentofylline enhances cerebral metabolic response to auditory memory stimulation in Alzheimer’s disease. J Neurol Sci (in press)Google Scholar
  43. Mielke R, Herholz K, Grand M, Kessler J, Heiss WD (1992) Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type. Neurobiol Aging 13: 93–98PubMedCrossRefGoogle Scholar
  44. Mielke R, Pietrzyk U, Jacobs A, Fink GR, Ichimiya A, Kessler J, Herholz K, Heiss WD (1994) HMPAO SPET and FDG PET in Alzheimer’s disease and vascular dementia: comparison of perfusion and metabolic pattern. Eur J Nucl Med 21: 1052–1060PubMedCrossRefGoogle Scholar
  45. Mielke R, Herholz K, Grand M, Kessler J, Heiss WD (1994) Clinical deterioration in probable Alzheimer’s disease correlates with progressive metabolic impairment of association areas. Dementia 5: 36–41PubMedGoogle Scholar
  46. Mielke R, Jacobs A, Kessler J, Pietrzyk U, Herholz K, Heiss WD (1995) Diagnostic accuracy of FDG PET and HMPAO SPECT for the differentiation between Alzheimer’s disease and vascular dementia depends on severity of disease. J Neurol 241: 35Google Scholar
  47. Mielke R, Schröder R, Fink G, Kessler J, Herholz K, Heiss WD (1996) Regional cerebral glucose metabolism and postmortem pathology in Alzheimer’s disease. Acta Neuropathol 91: 174–179PubMedCrossRefGoogle Scholar
  48. Mielke R, Ghaemi M, Kittner B, Kessler J, Szelies B, Herholz K, Heiss WD (1996) Propentofylline improves regional cerebral glucose metabolism and neuropsy-chological performance in vascular dementia. J Neurol Sci 141: 59–64PubMedCrossRefGoogle Scholar
  49. Morris JC, McKeel Jr DW, Fulling K, Torack RM, Berg L (1988) Validation of clinical diagnostic criteria for Alzheimer’s disease. Ann Neurol 24: 17–22PubMedCrossRefGoogle Scholar
  50. Nordberg A, Lilja A, Lundqvist H, Hartvig P, Amberla K, Viitanen M, Warpman U, Johansson M, Hellstrom-Lindahl E, Bjurling P (1992) Tacrine restores cholinergic nicotinic receptors and glucose-metabolism in Alzheimer patients as visualized by positron emission tomography. Neurobiol Aging 13: 747–758PubMedCrossRefGoogle Scholar
  51. Podreka I, Suess E, Goldenberg G, Steiner M, Brücke T, Müller CH, Lang W, Neirinckx RD, Deecke L (1987) Initial experience with Technetium-99m HM-PAO brain SPECT. J Nucl Med 28: 1657–1666PubMedGoogle Scholar
  52. Rapoport SI, Hatanpää K, Brady DR, Chandrasekaran K (1996) Brain energy metabolism, cognitive function and down-regulated oxidative phosphorylation in Alzheimer’s disease. Neurodegeneration 5: 473–476PubMedCrossRefGoogle Scholar
  53. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozzo JM, Brun A, Hofman A, Moody DM, O’Brien MD, Yamaguchi T, Grafman J, Drayer BP, Bennett DA, Fisher M, Ogata J, Kokmen E, Bermejo F, Wolf PA, Gorelick PB, Bick KL, Pajeau AK, Bell MA, DeCarli C, Culebras A, Korczyn AD, Bogousslavsky J, Hartmann A, Scheinberg P (1993) Vascular dementia: diagnostic criteria for research studies. Neurology 43: 250–260PubMedCrossRefGoogle Scholar
  54. Rossor MN, Iversen LL, Reynolds GP, Mountjoy CQ, Roth M (1984) Neurochemical characteristics of early and late onset type of Alzheimer’s disease. Br Med J 288: 961–964CrossRefGoogle Scholar
  55. Roth MN (1986) The association of clinical and neurobiological findings and its bearing on the classification and aetiology of Alzheimer’s disease. Br Med Bull 42: 42–50PubMedGoogle Scholar
  56. Sacquegna T, DeCarolis P, Daidone R, Dondi M (1988) Single-photon emission tomography with technetium Tc 99m hexamethylpropylene amine oxime in Binswanger’s disease. Arch Neurol 45: 603–604PubMedCrossRefGoogle Scholar
  57. Small GW. Kuhl DE, Riege WH, Fujikawa DG, Ashford JW, Metter EJ, Mazziotta JC (1989) Cerebral glucose metabolic patterns in Alzheimer’s disease. Effect of gender and age at dementia onset. Arch Gen Psychiat 46: 527–532CrossRefGoogle Scholar
  58. StGeorge-Hyslop PH, Haines JL, Farrer LA, Polinsky R, Broeckhoven C, Goate A, McLachlan DRC, Orr H, Bruni AC, Sorbi S, Rainero I, Foncin JF, Pollen D, Cantu JM, Tupler R, Voskresenskaya N, Mayeux R, Growdon J, Fried VA, Myers RH, Nee L, Backhovens H, Martin JJ, Rossor M, Owen MJ, Mullan M, Percy ME, Karlinsky H, Rich S, Heston L, Montesi M, Mortilla M, Nacmias N, Gusella JF, Hardy JA (1990) Genetic linkage studies suggest that Alzheimer’s disease is not a single homogenous disorder. Nature 347: 194–197CrossRefGoogle Scholar
  59. Szelies B, Herholz K, Pawlik G, Beil C, Wienhard K, Heiss WD (1986) Zerebraler Glukosestoffwechsel bei praeseniler Demenz vom Alzheimer Typ — Verlaufskontrolle unter Therapie mit muskarinergem Cholinagonisten. Fortschr Neurol Psychiat 11: 364–373CrossRefGoogle Scholar
  60. Szelies B, Karenberg A (1986) Störungen des Glukosestoffwechsels bei Pickscher Erkrankung. Fortschr Neurol Psychiat 54: 393–397PubMedCrossRefGoogle Scholar
  61. Tomlinson BE, Blessed G, Roth M (1968) Observations on the brains of non-demented old people. J Neurol Sci 7: 331–356PubMedCrossRefGoogle Scholar
  62. Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of demented old people. J Neurol Sci 11: 205–242PubMedCrossRefGoogle Scholar
  63. Tune L, Brandt J, Frost JJ, Harris G, Mayberg H, Steele C, Burns A, Sapp J, Folstein MF, Wagner HN (1991) Physostigmine in Alzheimer’s disease — effects on cognitive-functioning, cerebral glucose-metabolism analyzed by positron emission tomography and cerebral blood flow analyzed by single photon-emission tomography. Acta Psychiatr Scand 93 [Suppl 366]: 61–65CrossRefGoogle Scholar
  64. Weinstein HC, Haan J, van Royen EO, Derix MMA, Lanser JBK, van der Zant F, Dunnewold RJW, van Kroonenburgh MJPG, Pauwels EKJ, van der Velde EA, Hijdra A, Buruma OJS (1991) SPECT in the diagnosis of Alzheimer’s disease and multi-infarct dementia. Clin Neurol Neurosurg 93: 39–43PubMedCrossRefGoogle Scholar
  65. Weltgesundheitsorganisation (1991) Dilling H, Mombour W, Schmidt MH (eds) Internationale Klassifikation psychischer Störungen ICD 10 Kp V (F). Klinischdiagnostische Leitlinien. Huber, BernGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • R. Mielke
    • 1
  • W.-D. Heiss
    • 1
    • 2
  1. 1.Max-Planck-Institut für neurologische Forschung and Universitätsklinik für NeurologieKölnFederal Republic of Germany
  2. 2.Max-Planck-Institut für neurologische ForschungKölnFederal Republic of Germany

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