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Cerebral perfusion (HMPAO-SPECT) in patients with depression with cognitive impairment versus those with mild cognitive impairment and dementia of Alzheimer’s type: a semiquantitative and automated evaluation

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Comparative evaluation of regional brain perfusion measured by HMPAO-SPECT of patients with mild cognitive impairment (MCI), dementia of Alzheimer’s type (DAT) and depression with cognitive impairment (DCI).

Methods

A total of 736 patients were investigated because of suspected cognitive dysfunction. After exclusion of patients with other forms of dementia than DAT or relevant accompanying disorders, SPECT data from 149 MCI, 131 DAT and 127 DCI patients, and 123 controls without any cognitive impairment, were analysed. Relative cerebral blood flow of 34 anatomical regions was assessed with automated analysis software (BRASS).

Results

Calculation of global forebrain perfusion discriminated demented from nondemented patients. Compared to controls DCI patients showed hypoperfusion of the thalamus, lentiform nucleus and medial temporal cortex. MCI patients differed significantly from controls concerning perfusion in both hemispheric temporal and parietal areas, and in the (right hemispheric) posterior part of the cingulate gyrus. MCI and DCI patients differed in the parietal, temporal superior and right hemispheric cingulate gyrus posterior cortices. Global forebrain and regional perfusion was more extensively reduced in DAT patients and discriminated them from controls, and MCI and DCI patients. Frontal perfusion disturbance was only present in DAT patients.

Conclusion

Automated analysis of HMPAO-SPECT data from MCI patients showed significant perfusion deficits in regions also involved in DAT patients, but ROC analysis demonstrated only moderate sensitivity and specificity for differentiating DAT patients from controls and DCI patients. Frontal hypoperfusion seems to correspond with conversion from MCI to DAT. Finally, the results in DCI patients again raise the question of depression as an early symptom of neurodegeneration.

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References

  1. Scheltens P, Korf ES. Contribution of neuroimaging in the diagnosis of Alzheimer’s disease and other dementias. Curr Opin Neurol 2000;13:391–6.

    Article  PubMed  CAS  Google Scholar 

  2. DeCarli C. The role of neuroimaging in dementia. Clin Geriatr Med 2001;17:255–79.

    Article  PubMed  CAS  Google Scholar 

  3. Dougall NJ, Bruggink S, Ebmeier KP, et al. The clinical use of 99mTc-HMPAO in Alzheimer’s disease. In: Ebmeier KB, ed. SPECT in dementia. Adv Biol Psychiatry. Basel: Kager; 2003;22:4–37.

  4. Chow T. Structural imaging in the diagnosis of dementia. Alzheimers Dement 2007;3:333–5.

    Article  PubMed  Google Scholar 

  5. Kloppel S, Stonnington CM, Chu C, et al. Automatic classification of MR scans in Alzheimer’s disease. Brain 2008;131:681–9.

    Article  PubMed  Google Scholar 

  6. Kidron D, Black SE, Stanchev P, et al. Quantitative MR volumetry in Alzheimer’s disease. Topographic markers and the effects of sex and education. Neurology 1997;49:1504–12.

    PubMed  CAS  Google Scholar 

  7. Santens P, Petit H. Positron emission tomography in dementia. Acta Neurol Belg 1997;97:192–5.

    PubMed  CAS  Google Scholar 

  8. Hogh P, Teller AS, Hasselbalch S, Waldemar G. Visual rating and ROI-based parametric analysis of rCBF SPECT in patients with mild or questionable dementia: a comparative study. Dement Geriatr Cogn Disord 2007;24:429–33.

    Article  PubMed  Google Scholar 

  9. Jobst KA, Barnetson LP, Shepstone BJ. Accurate prediction of histologically confirmed Alzheimer’s disease and the differential diagnosis of dementia: the use of NINCDS-ADRDA and DSM-III-R criteria, SPECT, X-ray CT, and Apo E4 in medial temporal lobe dementias. Oxford Project to Investigate Memory and Aging. Int Psychogeriatr 1998;10:271–302.

    Article  PubMed  CAS  Google Scholar 

  10. Matsuda H, Mizumura S, Nagao T, et al. Automated discrimination between very early Alzheimer disease and controls using an easy Z-score imaging system for multicenter brain perfusion single-photon emission tomography. AJNR Am J Neuroradiol 2007;28:731–6.

    PubMed  CAS  Google Scholar 

  11. Staffen W, Schonauer U, Zauner H, et al. Brain perfusion SPECT in patients with mild cognitive impairment and Alzheimer's disease: comparison of a semiquantitative and a visual evaluation. J Neural Transm 2006;113:195–203.

    Article  PubMed  CAS  Google Scholar 

  12. Waragai M, Yamada T, Matsuda H. Evaluation of brain perfusion SPECT using an easy Z-score imaging system (eZIS) as an adjunct to early-diagnosis of neurodegenerative diseases. J Neurol Sci 2007;260:57–64.

    Article  PubMed  Google Scholar 

  13. Camargo EE. Brain SPECT in neurology and psychiatry. J Nucl Med 2001;42:611–23.

    PubMed  CAS  Google Scholar 

  14. Herholz K, Schopphoff H, Schmidt M, et al. Direct comparison of spatially normalized PET and SPECT scans in Alzheimer's disease. J Nucl Med 2002;43:21–6.

    PubMed  Google Scholar 

  15. Hoffman JM, Welsh-Bohmer KA, Hanson M, et al. FDG PET imaging in patients with pathologically verified dementia. J Nucl Med 2000;41:1920–8.

    PubMed  CAS  Google Scholar 

  16. Savoiardo M, Grisoli M. Imaging dementias. Eur Radiol 2001;11:484–92.

    Article  PubMed  CAS  Google Scholar 

  17. Jagust WJ. Neuroimaging in dementia. Neurol Clin 2000;18:885–902.

    Article  PubMed  CAS  Google Scholar 

  18. Caroli A, Testa C, Geroldi C, et al. Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment. J Neurol 2007;254:1698–707.

    Article  PubMed  CAS  Google Scholar 

  19. Encinas M, De Juan R, Marcos A, et al. Regional cerebral blood flow assessed with 99mTc-ECD SPET as a marker of progression of mild cognitive impairment to Alzheimer's disease. Eur J Nucl Med Mol Imaging 2003;30:1473–80.

    Article  PubMed  Google Scholar 

  20. Huang C, Wahlund LO, Svensson L, Winblad B, Julin P. Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment. BMC Neurol 2002;2:9.

    Article  PubMed  Google Scholar 

  21. Johnson KA, Moran EK, Becker JA, Blacker D, Fischman AJ, Albert MS. Single photon emission computed tomography perfusion differences in mild cognitive impairment. J Neurol Neurosurg Psychiatry 2007;78:240–7.

    Article  PubMed  CAS  Google Scholar 

  22. Matsuda H. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease. Ann Nucl Med 2001;15:85–92.

    Article  PubMed  CAS  Google Scholar 

  23. Okomura N, Shinkawa M, Arai H, et al. Prediction of progression in patients with mild cognitive impairment using IMP-SPECT. Nippon Ronen Igakkai Zasshi 2000;37:974–8.

    Google Scholar 

  24. Fleming JS, Kemp PM, Bolt L, Goatman KA. Measurement of cerebral perfusion volume and 99mTc-HMPAO uptake using SPECT in controls and patients with Alzheimer’s disease. Nucl Med Commun 2002;23:1057–64.

    Article  PubMed  CAS  Google Scholar 

  25. Van Laere KJ, Warwick J, Versijpt J, Goethals I, Audenaert K, Van Heerden B, et al. Analysis of clinical brain SPECT data based on anatomic standardization and reference to normal data: an ROC-based comparison of visual, semiquantitative, and voxel-based methods. J Nucl Med 2002;43:458–69.

    PubMed  Google Scholar 

  26. Devanand DP, Sano M, Tang MX, et al. Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community. Arch Gen Psychiatry 1996;53(2):175–82.

    PubMed  CAS  Google Scholar 

  27. Palmer K, Berger AK, Monastero R, et al. Predictors of progression from mild cognitive impairment to Alzheimer disease. Neurology 2007;68(19):1596–602.

    Article  PubMed  CAS  Google Scholar 

  28. Geerlings MI, den Heijer T, Koudstaal PJ, et al. History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease. Neurology 2008;70(15):1258–64.

    Article  PubMed  CAS  Google Scholar 

  29. Crowe SF, Hoogenraad K. Differentiation of dementia of the Alzheimer’s type from depression with cognitive impairment on the basis of a cortical versus subcortical pattern of cognitive deficit. Arch Clin Neuropsychol 2000;15:9–19.

    PubMed  CAS  Google Scholar 

  30. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98.

    Article  PubMed  CAS  Google Scholar 

  31. Wechsler D. A standardized memory scale for clinical use. J Psychol 1945;19:87–95.

    Google Scholar 

  32. Dahl G. Reduzierter Wechsler-Intelligenztest. Göttingen: Hogrefe; 1986.

  33. Lehrl S, Merz J, Burkhard G, Fischer S. Mehrfachwahl-Wortschatz-Inteligenztest. Balingen: Spitta Verlag; 2005.

    Google Scholar 

  34. Oswald WD, Fleischmann UM. Nürnberger-Alters-Inventar. Göttingen: Hogrefe; 1997.

  35. Zung WWK. Depressions-Status-Inventar (DSI). Fremdbeurteilungsskala. Weinheim: Beltz; 1986.

  36. Zerssen D, Koeller DM. Depressivitäts-Skala. Weinheim: Beltz; 1976.

  37. McKeith IG, Golasko D, Kosaka K, Perry EK, Dickson DW, Handsen LA. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996;47(5):1113–24.

    PubMed  CAS  Google Scholar 

  38. The Lund and Manchester Groups. Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 1994;57:416–8.

    Article  Google Scholar 

  39. Geldmacher DS, Whitehouse P. Evaluation of dementia. N Engl J Med 1996;335(5):330–6.

    Article  PubMed  CAS  Google Scholar 

  40. Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol Berl 1991;82:239–59.

    Article  PubMed  CAS  Google Scholar 

  41. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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;34:939–44.

    PubMed  CAS  Google Scholar 

  42. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1133–42.

    PubMed  CAS  Google Scholar 

  43. Folstein MF, McHugh PR. Dementia syndrome of depression. In: Katzman R, Terry RD, Bick KL, editors. Alzheimer’s disease: senile dementia and related disorders (Ageing, vol.7). New York: Raven Press; 1978. p. 87–92.

    Google Scholar 

  44. Chang LT. A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 1978;21:2–20.

    Google Scholar 

  45. Kanetaka H, Matsuda H, Asada T, Ohnishi T, Yamashita F, Imabayashi E, et al. Effects of partial volume correction on discrimination between very early Alzheimer's dementia and controls using brain perfusion SPECT. Eur J Nucl Med Mol Imaging 2004;31 7:975–80.

    Article  PubMed  Google Scholar 

  46. Pagani M, Salmaso D, Jonsson C, et al. Regional cerebral blood flow as assessed by principal component analysis and (99m)Tc-HMPAO SPET in healthy subjects at rest: normal distribution and effect of age and gender. Eur J Nucl Med Mol Imaging 2002;29:67–75.

    Article  PubMed  CAS  Google Scholar 

  47. Van Laere K, Versijpt J, Audenaert K, et al. 99mTc-ECD brain perfusion SPET: variability, asymmetry and effects of age and gender in healthy adults. Eur J Nucl Med 2001;28:873–87.

    Article  PubMed  Google Scholar 

  48. Matsuda H. Role of neuroimaging in Alzheimer’s disease, with emphasis on brain perfusion SPECT. J Nucl Med 2007;48:1289–300.

    Article  PubMed  Google Scholar 

  49. Uchida Y, Minoshima S, Okada S, Kawata T, Ito H. Diagnosis of dementia using perfusion SPECT imaging at the patient's initial visit to a cognitive disorder clinic. Clin Nucl Med 2006;31:764–73.

    Article  PubMed  Google Scholar 

  50. Duran FL, Zampieri FG, Bottino CC, Buchpiguel CA, Busatto GF. Voxel-based investigations of regional cerebral blood flow abnormalities in Alzheimer's disease using a single-detector SPECT system. Clinics 2007;62:377–84.

    Article  PubMed  Google Scholar 

  51. Hirsch C, Bartenstein P, Minoshima S, et al. Reduction of regional cerebral blood flow and cognitive impairment in patients with Alzheimer's disease: evaluation of an observer-independent analytic approach. Dement Geriatr Cogn Disord 1997;8:98–104.

    Article  PubMed  CAS  Google Scholar 

  52. Johnson KA, Jones K, Holman BL, et al. Preclinical prediction of Alzheimer's disease using SPECT. Neurology 1998;50:1563–71.

    PubMed  CAS  Google Scholar 

  53. Nobili F, Brugnolo A, Calvini P, et al. Resting SPECT-neuropsychology correlation in very mild Alzheimer's disease. Clin Neurophysiol 2005;116:364–75.

    Article  PubMed  CAS  Google Scholar 

  54. Rodriguez G, Morbelli S, Brugnolo A, et al. Global cognitive impairment should be taken into account in SPECT-neuropsychology correlations: the example of verbal memory in very mild Alzheimer's disease. Eur J Nucl Med Mol Imaging 2005;32:1186–92.

    Article  PubMed  CAS  Google Scholar 

  55. Vasic N, Walter H, Hose A, Wolf RC. Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study. J Affect Disord 2008;109:107–16.

    Article  PubMed  Google Scholar 

  56. Mu J, Xie P, Yang ZS, et al. 1H magnetic resonance spectroscopy study of thalamus in treatment resistant depressive patients. Neurosci Lett 2007;425:49–52.

    Article  PubMed  CAS  Google Scholar 

  57. Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 2001;11:240–9.

    Article  PubMed  CAS  Google Scholar 

  58. Greicius MD, Flores BH, Menon V, et al. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry 2007;62:429–37.

    Article  PubMed  Google Scholar 

  59. Matsuda H. The role of neuroimaging in mild cognitive impairment. Neuropathology 2007;27:570–7.

    Article  PubMed  Google Scholar 

  60. Yamaguchi S, Meguro K, Itoh M, et al. Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer's disease as shown by MRI and PET. J Neurol Neurosurg Psychiatry 1997;62:596–600.

    Article  PubMed  CAS  Google Scholar 

  61. Brown DR, Hunter R, Wyper DJ, et al. Longitudinal changes in cognitive function and regional cerebral function in Alzheimer's disease: a SPECT blood flow study. J Psychiatr Res 1996;30:109–26.

    Article  PubMed  CAS  Google Scholar 

  62. Nishimura T, Hashikawa K, Fukuyama H, et al. Decreased cerebral blood flow and prognosis of Alzheimer's disease: a multicenter HMPAO-SPECT study. Ann Nucl Med 2007;21:15–23.

    Article  PubMed  Google Scholar 

  63. Li Y, Rinne JO, Mosconi L, Pirraglia E, Rusinek H, Desanti S et al. Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer's disease. Eur J Nucl Med Mol Imaging 2008;35:2169–81

    Article  PubMed  Google Scholar 

  64. Van der Flier WM, Van Buchem AM, Weverlingh-Rijnsburger AW, Mutsaers ER, Bollen EL, Admiraal-Behloul F, et al. Memory complaints in patients with normal cognition are associated with smaller hippocampal volumes. J Neurol 2004;251:671–5.

    Article  PubMed  Google Scholar 

  65. Cho MJ, Lyoo IK, Lee DW, et al. Brain single photon emission computed tomography findings in depressive pseudodementia patients. J Affect Disord 2002;69:159–66.

    Article  PubMed  Google Scholar 

  66. Swets JA. Measuring the accuracy of diagnostic systems. Science 1988;240:1285–93.

    Article  PubMed  CAS  Google Scholar 

  67. Hampl H, Bürger K, Teipel SJ, Bokde AL, Zetterberg H, Blennow K. Core candidate neurochemical and imaging biomarkers of Alzheimer’s disease. Alzheimers Dement 2008;4:38–48.

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Markus Dimling for his technical support.

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Correspondence to W. Staffen.

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Staffen, W., Bergmann, J., Schönauer, U. et al. Cerebral perfusion (HMPAO-SPECT) in patients with depression with cognitive impairment versus those with mild cognitive impairment and dementia of Alzheimer’s type: a semiquantitative and automated evaluation. Eur J Nucl Med Mol Imaging 36, 801–810 (2009). https://doi.org/10.1007/s00259-008-1028-2

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  • DOI: https://doi.org/10.1007/s00259-008-1028-2

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