The spectrum of age-associated brain abnormalities: their measurement and histopathological correlates

  • F. Fazekas
  • R. Schmidt
  • R. Kleinert
  • P. Kapeller
  • G. Roob
  • E. Flooh
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 53)


Magnetic resonance imaging (MRI) has dramatically increased our ability to detect morphological abnormalities in relation to aging of the brain. Among those changes are alterations of the white matter which display high signal intensity on both proton density and T2-weighted images. They may be seen in the deep and subcortical white matter or in a periventricular location. In clinically asymptomatic individuals the reported prevalence ranges from 20% to 60% for deep and subcortical white matter hyperintensities and from 15% to 94% for periventricular changes. Besides different characteristics of the populations examined these wide ranges are a consequence of quite diverse rating schemes and measurement approaches. Inadequate grading of MRI hyperintensities may also explain some of the inconsistencies in the reported associations of white matter damage with cerebrovascular risk factors or cognitive functions. Therefore development of a commonly accepted rating scheme would be desirable. Histopathologic observations could lay the basis. Hyperintense periventricular capping of the frontal horns and a smooth halo of periventricular hyperintensity have been linked to disruption of the ependymal lining, subependymal gliosis and concomitant loss of myelin. Punctate lesions in the deep and subcortical white matter corresponded to minor perivascular reduction in myelin content possibly because of a lower permeability of thickened arteriolar walls. Larger patchy and confluent hyperintensities, however, appear to indicate more extensive ischemic damage consistent with advanced microangiopathy. In parallel, newer MRI techniques may also contribute to the delineation and separation of these various types of tissue alteration.


White Matter White Matter Hyperintensities White Matter Change Subcortical White Matter White Matter Damage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Awad IA, Spetzler RF, Hodak JA, Awad CA, Carey R (1986a) Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. I. Correlation with age and cerebrovascular risk factors. Stroke 17: 1084–1089Google Scholar
  2. Awad IA, Johnson PC, Spetzler RF, Hodak JA (1986b) Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlations. Stroke 17: 1090–1097PubMedCrossRefGoogle Scholar
  3. Bokura H, Kobayashi S, Yamaguchi S (1998) Distinguishing silent lacunar infarction from enlarged Virchow-Robin spaces: a magnetic resonance imaging and pathological study. J Neurol 245: 116–122PubMedCrossRefGoogle Scholar
  4. Brant-Zawadzki M, Fein G, VanDyke C, Kiernan R, Davenport L, DeGroot J (1985) MR imaging of the aging brain: patchy white-matter lesions and dementia. AJNR 6: 675–682PubMedGoogle Scholar
  5. Chui HC, Victoroff JI, Margolin D, Jagust W, Shankle R, Katzman R (1992) Criteria for thediagnosis of ischemic vascular dementia proposed by the State of California Alzheimer’s Disease Diagnostic and Treatment Centers. Neurology 42: 473–480PubMedCrossRefGoogle Scholar
  6. Easton JD (1997) Cognitive correlates of leukoaraiosis. Cerebrovasc Dis 7: 129–137CrossRefGoogle Scholar
  7. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MRI signal abnormalities at 1.5T in Alzheimer’s dementia and normal aging. AJNR 8: 421–426Google Scholar
  8. Fazekas F, Kleinert R, Offenbacher H, et al (1991) The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR 12: 915–921PubMedGoogle Scholar
  9. Fazekas F, Kleinert R, Offenbacher H, et al (1993) Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 43: 1683–1689PubMedCrossRefGoogle Scholar
  10. Fazekas F, Schmidt R, Kapeller P, Offenbacher H, Reinhart B, Eber B (1996) Factors modulating the extent of MRI white matter hyperintensities in the normal elderly population. Neurology 46: A133 (Abstract)Google Scholar
  11. Fazekas F, Schmidt R, Scheltens Ph (1998) Pathophysiologic mechanisms in the development of age-related white matter changes of the brain. Eur Neurol (in press)Google Scholar
  12. George AE, de Leon MJ, Gentes CT, et al (1986) Leukoencephalopathy in normal and pathologic aging. I. CT of brain lucencies. AJNR 7: 561–56PubMedGoogle Scholar
  13. Grafton ST, Sumi SM, Stimac GK, Alvord EC Jr, Shaw CM, Nochlin D (1991) Comparison of postmortem magnetic resonance imaging and neuropathologic findings in the cerebral white matter. Arch Neurol 48: 293–298PubMedCrossRefGoogle Scholar
  14. Hachinski V, Potter P, Merskey H (1987) Leuko-araiosis. Arch Neurol 44: 21–23PubMedCrossRefGoogle Scholar
  15. Inzitari D, Diaz F, Fox A, et al (1987) Vascular risk factors and leuko-araiosis. Arch Neurol 44: 42–47PubMedCrossRefGoogle Scholar
  16. Jernigan TL, Press GA, Hesselink JR (1990) Methods for measuring brain morphologic features on magnetic resonance images. Validation and normal aging. Arch Neurol 47: 27–32PubMedCrossRefGoogle Scholar
  17. Kapeller P, Ropele S, Fazekas F (1998) White matter imaging: technical considerations including histopathologic correlation. In: Pantoni L, Inzitari D, Wallin A (eds) The matter of white matter: clinical and pathophysiological aspects of white matter disease related to cognitive decline and vascular dementia. ICG Publications, Dordrecht (in press)Google Scholar
  18. Kidron D, Black SE, Stanchev P, Buck B, Szalai JP, Parker J, Szekely C, Bronskill MJ (1997) Quantitative MR volumetry in Alzheimer’s disease. Topograhic markers and the effects of sex and education. Neurology 49: 1504–1512PubMedCrossRefGoogle Scholar
  19. Kirkpatrick JB, Hayman LA (1987) White-matter lesions in MR imaging of clinically healthy brains of elderly subjects: possible pathologic basis. Radiology 162: 509–511PubMedGoogle Scholar
  20. Leifer D, Buonanno FS, Richardson EP Jr (1990) Clinicopathologic correlations of cranial magnetic resonance imaging of periventricular white matter. Neurology 40: 911–918PubMedCrossRefGoogle Scholar
  21. Mäntylä R, Erkinjuntti T, Salonen O, et al (1997) Variable agreement between visual rating scales for white matter hyperintensities on MRI. Stroke 28: 1614–1623PubMedCrossRefGoogle Scholar
  22. Munoz DG, Hastak SM, Harper B, Lee D, Hachinski VC (1993) Pathologic correlates of increased signals of the centrum ovale on magnetic resonance imaging. Arch Neurol 50: 492–497PubMedCrossRefGoogle Scholar
  23. Pantoni L, Garcia JH (1995) The significance of cerebral white matter abnormalities 100 years after Binswanger’s report. A review. Stroke 26: 1293–1301CrossRefGoogle Scholar
  24. Rezek DL, Morris JC, Fulling KH, Gado MH (1987) Periventricular white matter lucencies in senile dementia of the Alzheimer type and in normal aging. Neurology 37: 1365–1368PubMedCrossRefGoogle Scholar
  25. Roman GC, Tatemichi TK, Erkinjuntti T, et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43: 250–260PubMedCrossRefGoogle Scholar
  26. Scarpelli M, Salvolini U, Diamanti L, Montironi R, Chiaromoni L, Maricotti M (1994) MRI and pathological examination of post-mortem brains: the problem of white matter high signal areas. Neuroradiology 36: 393–398PubMedCrossRefGoogle Scholar
  27. Scheltens P, Barkhof F, Leys D, Wolters EC, Ravid R, Kamphorst W (1995) Histopathologic correlates of white matter changes on MRI in Alzheimer’s disease and normal aging. Neurology 45: 883–888PubMedCrossRefGoogle Scholar
  28. Scheltens PH, Erkinjuntti T, Leys D, et al (1998) White matter changes on CT and MRI. An overview of visual rating scales. Eur Neurol 39: 80–89PubMedCrossRefGoogle Scholar
  29. Schmidt R, Fazekas F, Offenbacher H, Dusek T, Zach E, Reinhart B, Grieshofer P, Freidl W, Eber B, Schumacher M, Koch M, Lechner H (1993) Neuropsychological correlates of MRI white matter hyperintensities: a study of 150 normal volunteers. Neurology 43: 2490–2494PubMedCrossRefGoogle Scholar
  30. Schmidt R, Fazekas F, Kapeller P, Schmidt H, Lechner A (1998a) White matter changes and cognitive decline in non-demented subjects. In: Leys D, Pasquier F, Schelten P (eds) Stroke and Alzheimer’s disease. ICG Publications Dordrecht (Current Issues in Neurodegenerative Disorders) (in press)Google Scholar
  31. Schmidt R, Fazekas F, Offenbacher H, Kapeller P, Schmidt H, Roob G (1998b) Prevalence and risk factors for white matter damage. In: Fazekas F, Schmidt R, Alavi A (eds) Neuroimaging of normal aging and uncommon causes of dementia. ICG Publications Dordrecht (Current Issues in Neurodegenerative Disorders) (in press)Google Scholar
  32. Steingart A, Hachinski V, Lau C, et al (1987) Cognitive and neurologic findings in subjects with diffuse white matter lucencies on computed tomographic scan (Leuko-Araiosis). Arch Neurol 44: 32–35PubMedCrossRefGoogle Scholar
  33. Stout JC, Jernigan TL, Archibald SL, Salmon DP (1996) Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type. Arch Neurol 53: 742–749PubMedCrossRefGoogle Scholar
  34. Sze G, De Armond SJ, Brant-Zawadzki M, Davis RL, Norman D, Newton DH (1986) Foci of MRI signal (pseudo-lesions) anterior to the frontal horns: histologic correlations of a normal finding. AJNR 17: 381–387Google Scholar
  35. Zimmerman RD, Fleming CA, Lee BCP, et al (1986) Periventricular hyperintensity as seen by magnetic resonance: prevalence and significance. AJNR 7: 13–20Google Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • F. Fazekas
    • 1
  • R. Schmidt
    • 1
  • R. Kleinert
    • 2
  • P. Kapeller
    • 1
  • G. Roob
    • 3
  • E. Flooh
    • 3
  1. 1.Department of NeurologyKarl-Franzens University GrazAustria
  2. 2.MR Institute, Karl-Franzens UniversityGrazAustria
  3. 3.Institute of Pathology, Karl-Franzens UniversityGrazAustria

Personalised recommendations