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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1994 Mar;57(3):285–295. doi: 10.1136/jnnp.57.3.285

Heterogeneity of neocortical cerebral blood flow deficits in dementia of the Alzheimer type: a [99mTc]-d,l-HMPAO SPECT study.

G Waldemar 1, P Bruhn 1, M Kristensen 1, A Johnsen 1, O B Paulson 1, N A Lassen 1
PMCID: PMC1072816  PMID: 8158175

Abstract

Regional cerebral blood flow (rCBF) was measured with high resolution brain dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) in 25 patients with probable Alzheimer's disease and in 25 control subjects, selected according to rigorous inclusion and exclusion criteria. The aim was to analyse the topography of rCBF deficits in individual patients. In the group of patients with Alzheimer's disease as a whole, global CBF was reduced, but a factorial analysis of variance did not show disproportionate reduction of rCBF in any brain region. A parametric analysis of the rCBF data in individual patients was carried out with reference to normal values for internal rCBF ratios and to 13 different abnormal rCBF patterns. These theoretical patterns were predefined by showing significant hypoperfusion in at least one, or in any relevant combination of two, three, or four, of four major brain regions (a left and right frontal and a left and right posterior region). All patients with Alzheimer's disease and none of the control subjects had an abnormal rCBF pattern. Eleven of the 13 different patterns were seen in the patients. Frontal changes were seen in 19 (76%) of the patients, more often than previously reported. No single Alzheimer's disease pattern could be derived from our data. The number of regions with hypoperfusion, but not the presence of frontal changes, correlated significantly with the duration of disease. It is concluded that a clinical diagnosis of probable Alzheimer's disease is associated with heterogeneous patterns of rCBF deficits as measured with SPECT and [99mTc]-d,l-HMPAO. This heterogeneity may reflect different stages of the disease or cognitive subtypes and help explain published discrepancies concerning the topography of hypoperfusion in Alzheimer's disease. An analysis of individual rCBF data may add important information in the investigation of diseases with heterogeneous effects on the brain.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akiyama H., Harrop R., McGeer P. L., Peppard R., McGeer E. G. Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease. Neurology. 1989 Apr;39(4):541–548. doi: 10.1212/wnl.39.4.541. [DOI] [PubMed] [Google Scholar]
  2. Andersen A. R., Friberg H. H., Schmidt J. F., Hasselbalch S. G. Quantitative measurements of cerebral blood flow using SPECT and [99mTc]-d,l-HM-PAO compared to xenon-133. J Cereb Blood Flow Metab. 1988 Dec;8(6):S69–S81. doi: 10.1038/jcbfm.1988.35. [DOI] [PubMed] [Google Scholar]
  3. Blessed G., Tomlinson B. E., Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968 Jul;114(512):797–811. doi: 10.1192/bjp.114.512.797. [DOI] [PubMed] [Google Scholar]
  4. Braak H., Braak E., Bohl J., Lang W. Alzheimer's disease: amyloid plaques in the cerebellum. J Neurol Sci. 1989 Nov;93(2-3):277–287. doi: 10.1016/0022-510x(89)90197-4. [DOI] [PubMed] [Google Scholar]
  5. Brun A., Englund E. A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study. Ann Neurol. 1986 Mar;19(3):253–262. doi: 10.1002/ana.410190306. [DOI] [PubMed] [Google Scholar]
  6. Brun A., Gustafson L. Distribution of cerebral degeneration in Alzheimer's disease. A clinico-pathological study. Arch Psychiatr Nervenkr (1970) 1976 Dec 31;223(1):15–33. doi: 10.1007/BF00367450. [DOI] [PubMed] [Google Scholar]
  7. Burns A., Philpot M. P., Costa D. C., Ell P. J., Levy R. The investigation of Alzheimer's disease with single photon emission tomography. J Neurol Neurosurg Psychiatry. 1989 Feb;52(2):248–253. doi: 10.1136/jnnp.52.2.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Celsis P., Goldman T., Henriksen L., Lassen N. A. A method for calculating regional cerebral blood flow from emission computed tomography of inert gas concentrations. J Comput Assist Tomogr. 1981 Oct;5(5):641–645. doi: 10.1097/00004728-198110000-00006. [DOI] [PubMed] [Google Scholar]
  9. Delecluse F., Andersen A. R., Waldemar G., Thomsen A. M., Kjaer L., Lassen N. A., Postiglione A. Cerebral blood flow in progressive aphasia without dementia. Case report, using 133xenon inhalation, technetium 99m hexamethylpropyleneamine oxime and single photon emission computerized tomography. Brain. 1990 Oct;113(Pt 5):1395–1404. doi: 10.1093/brain/113.5.1395. [DOI] [PubMed] [Google Scholar]
  10. Folstein M. F., Folstein S. E., McHugh P. R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar]
  11. Frackowiak R. S., Pozzilli C., Legg N. J., Du Boulay G. H., Marshall J., Lenzi G. L., Jones T. Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with oxygen-15 and positron tomography. Brain. 1981 Dec;104(Pt 4):753–778. doi: 10.1093/brain/104.4.753. [DOI] [PubMed] [Google Scholar]
  12. Frlich L., Eilles C., Ihl R., Maurer K., Lanczik M. Stage-dependent reductions of regional cerebral blood flow measured by HMPAO-SPECT in dementia of Alzheimer type. Psychiatry Res. 1989 Sep;29(3):347–350. doi: 10.1016/0165-1781(89)90085-1. [DOI] [PubMed] [Google Scholar]
  13. Geaney D. P., Soper N., Shepstone B. J., Cowen P. J. Effect of central cholinergic stimulation on regional cerebral blood flow in Alzheimer disease. Lancet. 1990 Jun 23;335(8704):1484–1487. doi: 10.1016/0140-6736(90)93028-n. [DOI] [PubMed] [Google Scholar]
  14. Gemmell H. G., Sharp P. F., Besson J. A., Crawford J. R., Ebmeier K. P., Davidson J., Smith F. W. Differential diagnosis in dementia using the cerebral blood flow agent 99mTc HM-PAO: a SPECT study. J Comput Assist Tomogr. 1987 May-Jun;11(3):398–402. doi: 10.1097/00004728-198705000-00005. [DOI] [PubMed] [Google Scholar]
  15. Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967 Dec;6(4):278–296. doi: 10.1111/j.2044-8260.1967.tb00530.x. [DOI] [PubMed] [Google Scholar]
  16. Haxby J. V., Duara R., Grady C. L., Cutler N. R., Rapoport S. I. Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease. J Cereb Blood Flow Metab. 1985 Jun;5(2):193–200. doi: 10.1038/jcbfm.1985.25. [DOI] [PubMed] [Google Scholar]
  17. Haxby J. V., Grady C. L., Koss E., Horwitz B., Schapiro M., Friedland R. P., Rapoport S. I. Heterogeneous anterior-posterior metabolic patterns in dementia of the Alzheimer type. Neurology. 1988 Dec;38(12):1853–1863. doi: 10.1212/wnl.38.12.1853. [DOI] [PubMed] [Google Scholar]
  18. Holman B. L., Johnson K. A., Gerada B., Carvalho P. A., Satlin A. The scintigraphic appearance of Alzheimer's disease: a prospective study using technetium-99m-HMPAO SPECT. J Nucl Med. 1992 Feb;33(2):181–185. [PubMed] [Google Scholar]
  19. Hunter R., McLuskie R., Wyper D., Patterson J., Christie J. E., Brooks D. N., McCulloch J., Fink G., Goodwin G. M. The pattern of function-related regional cerebral blood flow investigated by single photon emission tomography with 99mTc-HMPAO in patients with presenile Alzheimer's disease and Korsakoff's psychosis. Psychol Med. 1989 Nov;19(4):847–855. doi: 10.1017/s0033291700005560. [DOI] [PubMed] [Google Scholar]
  20. Jacoby R. J., Levy R., Dawson J. M. Computed tomography in the elderly: I. The normal population. Br J Psychiatry. 1980 Mar;136:249–255. doi: 10.1192/bjp.136.3.249. [DOI] [PubMed] [Google Scholar]
  21. Klinger A., de Leon M. J., George A. E., Miller J. D., Wolf A. P. Elevated cerebellar glucose metabolism in microvascular white matter disease: normal aging and Alzheimer's disease. J Cereb Blood Flow Metab. 1988 Jun;8(3):433–435. doi: 10.1038/jcbfm.1988.80. [DOI] [PubMed] [Google Scholar]
  22. Kuwabara Y., Ichiya Y., Otsuka M., Tahara T., Fukumura T., Gunasekera R., Ichimiya A., Masuda K. Comparison of I-123 IMP and Tc-99m HMPAO SPECT studies with PET in dementia. Ann Nucl Med. 1990 Nov;4(3):75–82. doi: 10.1007/BF03164600. [DOI] [PubMed] [Google Scholar]
  23. Martin A., Brouwers P., Lalonde F., Cox C., Teleska P., Fedio P., Foster N. L., Chase T. N. Towards a behavioral typology of Alzheimer's patients. J Clin Exp Neuropsychol. 1986 Oct;8(5):594–610. doi: 10.1080/01688638608405178. [DOI] [PubMed] [Google Scholar]
  24. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. 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. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  25. Mesulam M. M. Slowly progressive aphasia without generalized dementia. Ann Neurol. 1982 Jun;11(6):592–598. doi: 10.1002/ana.410110607. [DOI] [PubMed] [Google Scholar]
  26. Montaldi D., Brooks D. N., McColl J. H., Wyper D., Patterson J., Barron E., McCulloch J. Measurements of regional cerebral blood flow and cognitive performance in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1990 Jan;53(1):33–38. doi: 10.1136/jnnp.53.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Morris J. C., McKeel D. W., Jr, Fulling K., Torack R. M., Berg L. Validation of clinical diagnostic criteria for Alzheimer's disease. Ann Neurol. 1988 Jul;24(1):17–22. doi: 10.1002/ana.410240105. [DOI] [PubMed] [Google Scholar]
  28. Neary D., Snowden J. S., Shields R. A., Burjan A. W., Northen B., MacDermott N., Prescott M. C., Testa H. J. Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia. J Neurol Neurosurg Psychiatry. 1987 Sep;50(9):1101–1109. doi: 10.1136/jnnp.50.9.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Neirinckx R. D., Canning L. R., Piper I. M., Nowotnik D. P., Pickett R. D., Holmes R. A., Volkert W. A., Forster A. M., Weisner P. S., Marriott J. A. Technetium-99m d,l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion. J Nucl Med. 1987 Feb;28(2):191–202. [PubMed] [Google Scholar]
  30. O'Brien J. T., Eagger S., Syed G. M., Sahakian B. J., Levy R. A study of regional cerebral blood flow and cognitive performance in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1992 Dec;55(12):1182–1187. doi: 10.1136/jnnp.55.12.1182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Perani D., Di Piero V., Vallar G., Cappa S., Messa C., Bottini G., Berti A., Passafiume D., Scarlato G., Gerundini P. Technetium-99m HM-PAO-SPECT study of regional cerebral perfusion in early Alzheimer's disease. J Nucl Med. 1988 Sep;29(9):1507–1514. [PubMed] [Google Scholar]
  32. Reisberg B., Ferris S. H., de Leon M. J., Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982 Sep;139(9):1136–1139. doi: 10.1176/ajp.139.9.1136. [DOI] [PubMed] [Google Scholar]
  33. Risse S. C., Raskind M. A., Nochlin D., Sumi S. M., Lampe T. H., Bird T. D., Cubberley L., Peskind E. R. Neuropathological findings in patients with clinical diagnoses of probable Alzheimer's disease. Am J Psychiatry. 1990 Feb;147(2):168–172. doi: 10.1176/ajp.147.2.168. [DOI] [PubMed] [Google Scholar]
  34. Scheltens P., Barkhof F., Valk J., Algra P. R., van der Hoop R. G., Nauta J., Wolters E. C. White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer's disease. Evidence for heterogeneity. Brain. 1992 Jun;115(Pt 3):735–748. doi: 10.1093/brain/115.3.735. [DOI] [PubMed] [Google Scholar]
  35. Stokely E. M., Sveinsdottir E., Lassen N. A., Rommer P. A single photon dynamic computer assisted tomograph (DCAT) for imaging brain function in multiple cross sections. J Comput Assist Tomogr. 1980 Apr;4(2):230–240. doi: 10.1097/00004728-198004000-00022. [DOI] [PubMed] [Google Scholar]
  36. Terry R. D., Peck A., DeTeresa R., Schechter R., Horoupian D. S. Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol. 1981 Aug;10(2):184–192. doi: 10.1002/ana.410100209. [DOI] [PubMed] [Google Scholar]
  37. Tomlinson B. E., Blessed G., Roth M. Observations on the brains of demented old people. J Neurol Sci. 1970 Sep;11(3):205–242. doi: 10.1016/0022-510x(70)90063-8. [DOI] [PubMed] [Google Scholar]
  38. Waldemar G., Hasselbalch S. G., Andersen A. R., Delecluse F., Petersen P., Johnsen A., Paulson O. B. 99mTc-d,l-HMPAO and SPECT of the brain in normal aging. J Cereb Blood Flow Metab. 1991 May;11(3):508–521. doi: 10.1038/jcbfm.1991.95. [DOI] [PubMed] [Google Scholar]

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