Skip to main content

Advertisement

SpringerLink
Log in

Perfusion abnormalities in mild cognitive impairment and mild dementia in Alzheimer’s disease measured by pulsed arterial spin labeling MRI

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) and mild cognitive impairment (MCI), the transitional clinical stage between cognition in normal aging and dementia, have been linked to abnormalities in brain perfusion. Pulsed arterial spin labeling (PASL) is a magnetic resonance imaging (MRI) technique for evaluating brain perfusion. The present study aimed to determine regional perfusion abnormalities in 19 patients with mild dementia in AD and 24 patients with MCI as compared to 24 cognitively healthy elderly controls using PASL. In line with nuclear imaging methods, lower perfusion in patients with MCI and AD was found mainly in the parietal lobe, but also in angular and middle temporal areas as well as in the left middle occipital lobe and precuneus. Our data imply that PASL may be a valuable instrument for investigating perfusion changes in the transition from normal aging to dementia and indicate that it might become an alternative to nuclear imaging techniques in AD diagnostics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Alexopoulos P, Greim B, Nadler K, Martens U, Krecklow B, Domes G, Herpertz S, Kurz A (2006) Validation of the Addenbrooke’s cognitive examination for detecting early Alzheimer’s disease and mild vascular dementia in a German population. Dement Geriatr Cogn Disord 22:385–391

    Article  PubMed  CAS  Google Scholar 

  2. Alexopoulos P, Grimmer T, Perneczky R, Domes G, Kurz A (2006) Progression to dementia in clinical subtypes of mild cognitive impairment. Dement Geriatr Cogn Disord 22:27–34

    Article  PubMed  CAS  Google Scholar 

  3. Alsop DC, Casement M, de Bazelaire C, Fong T, Press DZ (2008) Hippocampal hyperperfusion in Alzheimer’s disease. Neuroimage 42:1267–1274

    Article  PubMed  Google Scholar 

  4. Alsop DC, Dai W, Grossman M, Detre JA (2010) Arterial spin labeling blood flow MRI: its role in the early characterization of Alzheimer’s disease. J Alzheimers Dis 20:871–880

    PubMed  Google Scholar 

  5. Ashburner J, Friston KJ (1999) Nonlinear spatial normalization using basis functions. Hum Brain Mapp 7:254–266

    Article  PubMed  CAS  Google Scholar 

  6. Bradley KM, O’Sullivan VT, Soper ND, Nagy Z, King EM, Smith AD, Shepstone BJ (2002) Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer’s disease. Brain 125:1772–1781

    Article  PubMed  CAS  Google Scholar 

  7. Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR (1998) A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med 40:383–396

    Article  PubMed  CAS  Google Scholar 

  8. Buxton RB, Uludag K, Dubowitz DJ, Liu TT (2004) Modeling the hemodynamic response to brain activation. Neuroimage 23(Suppl 1):S220–S233

    Article  PubMed  Google Scholar 

  9. Celone KA, Calhoun VD, Dickerson BC, Atri A, Chua EF, Miller SL, DePeau K, Rentz DM, Selkoe DJ, Blacker D, Albert MS, Sperling RA (2006) Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: an independent component analysis. J Neurosci 26:10222–10231

    Article  PubMed  CAS  Google Scholar 

  10. Chen W, Song X, Beyea S, D’Arcy R, Zhang Y, Rockwood K (2010) Advances in perfusion magnetic resonance imaging in Alzheimer’s disease. Alzheimers Dement 7(2):185–196

    Google Scholar 

  11. D’Esposito M, Deouell LY, Gazzaley A (2003) Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat Rev Neurosci 4:863–872

    Article  PubMed  Google Scholar 

  12. Dai W, Lopez OL, Carmichael OT, Becker JT, Kuller LH, Gach HM (2009) Mild cognitive impairment and alzheimer disease: patterns of altered cerebral blood flow at MR imaging. Radiology 250:856–866

    Article  PubMed  Google Scholar 

  13. de Leon MJ, Convit A, Wolf OT, Tarshish CY, DeSanti S, Rusinek H, Tsui W, Kandil E, Scherer AJ, Roche A, Imossi A, Thorn E, Bobinski M, Caraos C, Lesbre P, Schlyer D, Poirier J, Reisberg B, Fowler J (2001) Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-d-glucose/poitron-emission tomography (FDG/PET). Proc Natl Acad Sci U S A 98:10966–10971

    Article  PubMed  Google Scholar 

  14. Dickerson BC, Sperling RA (2008) Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer’s disease: insights from functional MRI studies. Neuropsychologia 46:1624–1635

    Article  PubMed  Google Scholar 

  15. Dougall NJ, Bruggink S, Ebmeier KP (2004) Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia. Am J Geriatr Psychiatry 12:554–570

    PubMed  Google Scholar 

  16. Drzezga A, Lautenschlager N, Siebner H, Riemenschneider M, Willoch F, Minoshima S, Schwaiger M, Kurz A (2003) Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer’s disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 30:1104–1113

    Article  PubMed  Google Scholar 

  17. Falkai P, Moller HJ (2010) Understanding mental disorders from neuronal networks to glial cells and proteomics. Eur Arch Psychiatry Clin Neurosci 260:441–442

    Article  PubMed  Google Scholar 

  18. Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  PubMed  CAS  Google Scholar 

  19. Fukumoto H, Cheung BS, Hyman BT, Irizarry MC (2002) Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol 59:1381–1389

    Article  PubMed  Google Scholar 

  20. Golay X, Petersen ET, Hui F (2005) Pulsed star labeling of arterial regions (PULSAR): a robust regional perfusion technique for high field imaging. Magn Reson Med 53:15–21

    Article  PubMed  Google Scholar 

  21. Grimmer T, Drzezga A, Kurz A (2010) Visualization of amyloid with positron emission tomography. Useful improvement in the diagnosis of dementia? Nervenarzt 81:602–606

    Article  PubMed  CAS  Google Scholar 

  22. Hanyu H, Shimizu S, Tanaka Y, Takasaki M, Koizumi K, Abe K (2004) Differences in regional cerebral blood flow patterns in male versus female patients with Alzheimer disease. Ajnr 25:1199–1204

    PubMed  Google Scholar 

  23. Heo S, Prakash RS, Voss MW, Erickson KI, Ouyang C, Sutton BP, Kramer AF (2010) Resting hippocampal blood flow, spatial memory and aging. Brain Res 1315:119–127

    Article  PubMed  CAS  Google Scholar 

  24. Herholz K, Carter SF, Jones M (2007) Positron emission tomography imaging in dementia. Br J Radiol 80(Spec No 2):S160–S167

    Article  PubMed  Google Scholar 

  25. Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL (1984) Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science 225:1168–1170

    Article  PubMed  CAS  Google Scholar 

  26. Jack CR Jr, Petersen RC, Xu YC, O’Brien PC, Smith GE, Ivnik RJ, Boeve BF, Waring SC, Tangalos EG, Kokmen E (1999) Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 52:1397–1403

    PubMed  Google Scholar 

  27. Jarstfer BS, Rich NM, Hobson RW 2nd, Geer TM (1980) Smoking, lipids, and atherosclerosis. Mil Med 145:521–524

    PubMed  CAS  Google Scholar 

  28. Johnson KA (2006) Amyloid imaging of Alzheimer’s disease using Pittsburgh Compound B. Curr Neurol Neurosci Rep 6:496–503

    Article  PubMed  Google Scholar 

  29. Johnson KA, Moran EK, Becker JA, Blacker D, Fischman AJ, Albert MS (2007) Single photon emission computed tomography perfusion differences in mild cognitive impairment. J Neurol Neurosurg Psychiatry 78:240–247

    Article  PubMed  CAS  Google Scholar 

  30. Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, Gorno-Tempini ML, Schuff N (2005) Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology 234:851–859

    Article  PubMed  Google Scholar 

  31. Luh WM, Wong EC, Bandettini PA, Hyde JS (1999) QUIPSS II with thin-slice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med 41:1246–1254

    Article  PubMed  CAS  Google Scholar 

  32. Mansfield P (1984) Real-time echo-planar imaging by NMR. Br Med Bull 40:187–190

    PubMed  CAS  Google Scholar 

  33. Martins-de-Souza D (2010) Is the word ‘biomarker’ being properly used by proteomics research in neuroscience? Eur Arch Psychiatry Clin Neurosci 260:561–562

    Article  PubMed  Google Scholar 

  34. McKhann G, Drachmann D, Folstein M, Katzmann R, Price D, Stadlan E (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 34:939–944

    Google Scholar 

  35. Minati L, Edginton T, Bruzzone MG, Giaccone G (2009) Current concepts in Alzheimer’s disease: a multidisciplinary review. Am J Alzheimers Dis Other Demen 24:95–121

    Article  PubMed  Google Scholar 

  36. Mosconi L, Tsui WH, De Santi S, Li J, Rusinek H, Convit A, Li Y, Boppana M, de Leon MJ (2005) Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis. Neurology 64:1860–1867

    Article  PubMed  CAS  Google Scholar 

  37. Nichols T, Hayasaka S (2003) Controlling the familywise error rate in functional neuroimaging: a comparative review. Stat Methods Med Res 12:419–446

    Article  PubMed  Google Scholar 

  38. Nöth U, Meadows GE, Kotajima F, Deichmann R, Corfield DR, Turner R (2006) Cerebral vascular response to hypercapnia: determination with perfusion MRI at 1.5 and 3.0 Tesla using a pulsed arterial spin labeling technique. J Magn Reson Imaging 24:1229–1235

    Article  PubMed  Google Scholar 

  39. Pertoldi C, Hansen MM, Loeschcke V, Madsen AB, Jacobsen L, Baagoe H (2001) Genetic consequences of population decline in the European otter (Lutra lutra): an assessment of microsatellite DNA variation in Danish otters from 1883 to 1993. Proc Biol Sci 268:1775–1781

    Article  PubMed  CAS  Google Scholar 

  40. Placanica L, Zhu L, Li YM (2009) Gender- and age-dependent gamma-secretase activity in mouse brain and its implication in sporadic Alzheimer disease. PLoS One 4:e5088

    Article  PubMed  Google Scholar 

  41. Price JL, Davis PB, Morris JC, White DL (1991) The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer’s disease. Neurobiol Aging 12:295–312

    Article  PubMed  CAS  Google Scholar 

  42. Raji CA, Becker JT, Tsopelas ND, Price JC, Mathis CA, Saxton JA, Lopresti BJ, Hoge JA, Ziolko SK, DeKosky ST, Klunk WE (2008) Characterizing regional correlation, laterality and symmetry of amyloid deposition in mild cognitive impairment and Alzheimer’s disease with Pittsburgh Compound B. J Neurosci Methods 172:277–282

    Article  PubMed  CAS  Google Scholar 

  43. Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 14:45–53

    Article  PubMed  CAS  Google Scholar 

  44. Roberts DA, Detre JA, Bolinger L, Insko EK, Leigh JS Jr (1994) Quantitative magnetic resonance imaging of human brain perfusion at 1.5 T using steady-state inversion of arterial water. Proc Natl Acad Sci USA 91:33–37

    Article  PubMed  CAS  Google Scholar 

  45. Rodriguez G, Warkentin S, Risberg J, Rosadini G (1988) Sex differences in regional cerebral blood flow. J Cereb Blood Flow Metab 8:783–789

    Article  PubMed  CAS  Google Scholar 

  46. Rosazza C, Minati L, Ghielmetti F, Maccagnano E, Erbetta A, Villani F, Epifani F, Spreafico R, Bruzzone MG (2009) Engagement of the medial temporal lobe in verbal and nonverbal memory: assessment with functional MR imaging in healthy subjects. AJNR Am J Neuroradiol 30:1134–1141

    Article  PubMed  CAS  Google Scholar 

  47. Thalmann B, Monsch A (1997) The consortium to establish a registry for Alzheimer’s disease. Neuropsychologische Testbatterie. Memory Clinic Basel, Basel

    Google Scholar 

  48. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–289

    Article  PubMed  CAS  Google Scholar 

  49. Warkentin S, Ohlsson M, Wollmer P, Edenbrandt L, Minthon L (2004) Regional cerebral blood flow in Alzheimer’s disease: classification and analysis of heterogeneity. Dement Geriatr Cogn Disord 17:207–214

    Article  PubMed  Google Scholar 

  50. WHO (1994) Internationale Klassifikation psychischer Störungen, ICD-10 Kapitel V(F) Forschungskriterien. Hans Huber, Bern

    Google Scholar 

  51. Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC (2004) Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246

    Article  PubMed  CAS  Google Scholar 

  52. Wong EC, Buxton RB, Frank LR (1998) Quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSS II). Magn Reson Med 39:702–708

    Article  PubMed  CAS  Google Scholar 

  53. Worsley KJ (2003) Detecting activation in fMRI data. Stat Methods Med Res 12:401–418

    Article  PubMed  CAS  Google Scholar 

  54. Zetterberg H, Blennow K, Hanse E (2010) Amyloid beta and APP as biomarkers for Alzheimer’s disease. Exp Gerontol 45:23–29

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank all the healthy and diseased volunteers who participated in this study. AMW is supported by the German Federal Ministry of Education and Research, BMBF grant 01EV0710.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der TU München, Ismaninger Str. 22, 81675, München, Germany

    Panagiotis Alexopoulos, Christian Sorg, Timo Grimmer, Robert Perneczky & Alexander Kurz

  2. Department of Neuroradiology, Technische Universität München, Munich, Germany

    Christian Sorg, Annette Förschler, Afra Wohlschläger, Claus Zimmer & Christine Preibisch

  3. Department of Psychiatry, University of Patras, Rion, Patras, Greece

    Maria Skokou

  4. Department of Neurology, Technische Universität München, München, Germany

    Christine Preibisch

Authors
  1. Panagiotis Alexopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Sorg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annette Förschler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Timo Grimmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Skokou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Afra Wohlschläger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert Perneczky
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Claus Zimmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alexander Kurz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Christine Preibisch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Panagiotis Alexopoulos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alexopoulos, P., Sorg, C., Förschler, A. et al. Perfusion abnormalities in mild cognitive impairment and mild dementia in Alzheimer’s disease measured by pulsed arterial spin labeling MRI. Eur Arch Psychiatry Clin Neurosci 262, 69–77 (2012). https://doi.org/10.1007/s00406-011-0226-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-011-0226-2

Keywords

Search

Navigation