Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2004 Jun;75(6):822–827. doi: 10.1136/jnnp.2003.019273

White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease

A Capizzano 1, L Acion 1, T Bekinschtein 1, M Furman 1, H Gomila 1, A Martinez 1, R Mizrahi 1, S Starkstein 1
PMCID: PMC1739041  PMID: 15145992

Abstract

Background and objective: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and examined the association between WMH and structural and cognitive variables.

Methods: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates.

Results: Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R2 = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks.

Conclusion: Objective measurements of tissue volumes in AD demonstrated that WMH are significantly related to cortical atrophy and neuropsychological impairment.

Full Text

The Full Text of this article is available as a PDF (306.4 KB).

Selected References

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

  1. Andreasen N. C., Rajarethinam R., Cizadlo T., Arndt S., Swayze V. W., 2nd, Flashman L. A., O'Leary D. S., Ehrhardt J. C., Yuh W. T. Automatic atlas-based volume estimation of human brain regions from MR images. J Comput Assist Tomogr. 1996 Jan-Feb;20(1):98–106. doi: 10.1097/00004728-199601000-00018. [DOI] [PubMed] [Google Scholar]
  2. Barber R., Scheltens P., Gholkar A., Ballard C., McKeith I., Ince P., Perry R., O'Brien J. White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging. J Neurol Neurosurg Psychiatry. 1999 Jul;67(1):66–72. doi: 10.1136/jnnp.67.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bondareff W., Raval J., Woo B., Hauser D. L., Colletti P. M. Magnetic resonance imaging and the severity of dementia in older adults. Arch Gen Psychiatry. 1990 Jan;47(1):47–51. doi: 10.1001/archpsyc.1990.01810130049007. [DOI] [PubMed] [Google Scholar]
  4. Boone K. B., Miller B. L., Lesser I. M., Mehringer C. M., Hill-Gutierrez E., Goldberg M. A., Berman N. G. Neuropsychological correlates of white-matter lesions in healthy elderly subjects. A threshold effect. Arch Neurol. 1992 May;49(5):549–554. doi: 10.1001/archneur.1992.00530290141024. [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., Englund E. Regional pattern of degeneration in Alzheimer's disease: neuronal loss and histopathological grading. Histopathology. 1981 Sep;5(5):549–564. doi: 10.1111/j.1365-2559.1981.tb01818.x. [DOI] [PubMed] [Google Scholar]
  7. Buschke H., Fuld P. A. Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology. 1974 Nov;24(11):1019–1025. doi: 10.1212/wnl.24.11.1019. [DOI] [PubMed] [Google Scholar]
  8. Capizzano A. A., Schuff N., Amend D. L., Tanabe J. L., Norman D., Maudsley A. A., Jagust W., Chui H. C., Fein G., Segal M. R. Subcortical ischemic vascular dementia: assessment with quantitative MR imaging and 1H MR spectroscopy. AJNR Am J Neuroradiol. 2000 Apr;21(4):621–630. [PMC free article] [PubMed] [Google Scholar]
  9. De Renzi E., Faglioni P. Normative data and screening power of a shortened version of the Token Test. Cortex. 1978 Mar;14(1):41–49. doi: 10.1016/s0010-9452(78)80006-9. [DOI] [PubMed] [Google Scholar]
  10. DeCarli C., Murphy D. G., Tranh M., Grady C. L., Haxby J. V., Gillette J. A., Salerno J. A., Gonzales-Aviles A., Horwitz B., Rapoport S. I. The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology. 1995 Nov;45(11):2077–2084. doi: 10.1212/wnl.45.11.2077. [DOI] [PubMed] [Google Scholar]
  11. Englund E., Brun A., Alling C. White matter changes in dementia of Alzheimer's type. Biochemical and neuropathological correlates. Brain. 1988 Dec;111(Pt 6):1425–1439. doi: 10.1093/brain/111.6.1425. [DOI] [PubMed] [Google Scholar]
  12. Fazekas F., Kleinert R., Offenbacher H., Schmidt R., Kleinert G., Payer F., Radner H., Lechner H. Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology. 1993 Sep;43(9):1683–1689. doi: 10.1212/wnl.43.9.1683. [DOI] [PubMed] [Google Scholar]
  13. Fein G., Di Sclafani V., Tanabe J., Cardenas V., Weiner M. W., Jagust W. J., Reed B. R., Norman D., Schuff N., Kusdra L. Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease. Neurology. 2000 Dec 12;55(11):1626–1635. doi: 10.1212/wnl.55.11.1626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Giubilei F., Bastianello S., Paolillo A., Gasperini C., Tisei P., Casini A. R., Gragnani A., Bozzao L., Fieschi C. Quantitative magnetic resonance analysis in vascular dementia. J Neurol. 1997 Apr;244(4):246–251. doi: 10.1007/s004150050079. [DOI] [PubMed] [Google Scholar]
  16. Hachinski V. C., Potter P., Merskey H. Leuko-araiosis. Arch Neurol. 1987 Jan;44(1):21–23. doi: 10.1001/archneur.1987.00520130013009. [DOI] [PubMed] [Google Scholar]
  17. Hampel H., Teipel S. J., Alexander G. E., Horwitz B., Teichberg D., Schapiro M. B., Rapoport S. I. Corpus callosum atrophy is a possible indicator of region- and cell type-specific neuronal degeneration in Alzheimer disease: a magnetic resonance imaging analysis. Arch Neurol. 1998 Feb;55(2):193–198. doi: 10.1001/archneur.55.2.193. [DOI] [PubMed] [Google Scholar]
  18. Harris G., Andreasen N. C., Cizadlo T., Bailey J. M., Bockholt H. J., Magnotta V. A., Arndt S. Improving tissue classification in MRI: a three-dimensional multispectral discriminant analysis method with automated training class selection. J Comput Assist Tomogr. 1999 Jan-Feb;23(1):144–154. doi: 10.1097/00004728-199901000-00030. [DOI] [PubMed] [Google Scholar]
  19. Hughes C. P., Berg L., Danziger W. L., Coben L. A., Martin R. L. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982 Jun;140:566–572. doi: 10.1192/bjp.140.6.566. [DOI] [PubMed] [Google Scholar]
  20. Inzitari D. Age-related white matter changes and cognitive impairment. Ann Neurol. 2000 Feb;47(2):141–143. [PubMed] [Google Scholar]
  21. Ishii N., Nishihara Y., Imamura T. Why do frontal lobe symptoms predominate in vascular dementia with lacunes? Neurology. 1986 Mar;36(3):340–345. doi: 10.1212/wnl.36.3.340. [DOI] [PubMed] [Google Scholar]
  22. Leys D., Soetaert G., Petit H., Fauquette A., Pruvo J. P., Steinling M. Periventricular and white matter magnetic resonance imaging hyperintensities do not differ between Alzheimer's disease and normal aging. Arch Neurol. 1990 May;47(5):524–527. doi: 10.1001/archneur.1990.00530050040010. [DOI] [PubMed] [Google Scholar]
  23. Libon D. J., Bogdanoff B., Cloud B. S., Skalina S., Giovannetti T., Gitlin H. L., Bonavita J. Declarative and procedural learning, quantitative measures of the hippocampus, and subcortical white alterations in Alzheimer's disease and ischaemic vascular dementia. J Clin Exp Neuropsychol. 1998 Feb;20(1):30–41. doi: 10.1076/jcen.20.1.30.1490. [DOI] [PubMed] [Google Scholar]
  24. Liu C. K., Miller B. L., Cummings J. L., Mehringer C. M., Goldberg M. A., Howng S. L., Benson D. F. A quantitative MRI study of vascular dementia. Neurology. 1992 Jan;42(1):138–143. doi: 10.1212/wnl.42.1.138. [DOI] [PubMed] [Google Scholar]
  25. Longstreth W. T., Jr, Manolio T. A., Arnold A., Burke G. L., Bryan N., Jungreis C. A., Enright P. L., O'Leary D., Fried L. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke. 1996 Aug;27(8):1274–1282. doi: 10.1161/01.str.27.8.1274. [DOI] [PubMed] [Google Scholar]
  26. Mielke R., Herholz K., Grond M., Kessler J., Heiss W. D. Severity of vascular dementia is related to volume of metabolically impaired tissue. Arch Neurol. 1992 Sep;49(9):909–913. doi: 10.1001/archneur.1992.00530330031011. [DOI] [PubMed] [Google Scholar]
  27. Scheltens P., Barkhof F., Leys D., Wolters E. C., Ravid R., Kamphorst W. Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging. Neurology. 1995 May;45(5):883–888. doi: 10.1212/wnl.45.5.883. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Scheltens P., Erkinjunti T., Leys D., Wahlund L. O., Inzitari D., del Ser T., Pasquier F., Barkhof F., Mäntylä R., Bowler J. White matter changes on CT and MRI: an overview of visual rating scales. European Task Force on Age-Related White Matter Changes. Eur Neurol. 1998;39(2):80–89. doi: 10.1159/000007921. [DOI] [PubMed] [Google Scholar]
  30. Smith C. D., Snowdon D. A., Wang H., Markesbery W. R. White matter volumes and periventricular white matter hyperintensities in aging and dementia. Neurology. 2000 Feb 22;54(4):838–842. doi: 10.1212/wnl.54.4.838. [DOI] [PubMed] [Google Scholar]
  31. Starkstein S. E., Sabe L., Vazquez S., Teson A., Petracca G., Chemerinski E., Di Lorenzo G., Leiguarda R. Neuropsychological, psychiatric, and cerebral blood flow findings in vascular dementia and Alzheimer's disease. Stroke. 1996 Mar;27(3):408–414. doi: 10.1161/01.str.27.3.408. [DOI] [PubMed] [Google Scholar]
  32. Starkstein S. E., Sabe L., Vázquez S., Di Lorenzo G., Martínez A., Petracca G., Tesón A., Chemerinski E., Leiguarda R. Neuropsychological, psychiatric, and cerebral perfusion correlates of leukoaraiosis in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1997 Jul;63(1):66–73. doi: 10.1136/jnnp.63.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stout J. C., Jernigan T. L., Archibald S. L., Salmon D. P. Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type. Arch Neurol. 1996 Aug;53(8):742–749. doi: 10.1001/archneur.1996.00550080056013. [DOI] [PubMed] [Google Scholar]
  34. Sultzer D. L., Mahler M. E., Cummings J. L., Van Gorp W. G., Hinkin C. H., Brown C. Cortical abnormalities associated with subcortical lesions in vascular dementia. Clinical and position emission tomographic findings. Arch Neurol. 1995 Aug;52(8):773–780. doi: 10.1001/archneur.1995.00540320049012. [DOI] [PubMed] [Google Scholar]
  35. Swan G. E., DeCarli C., Miller B. L., Reed T., Wolf P. A., Carmelli D. Biobehavioral characteristics of nondemented older adults with subclinical brain atrophy. Neurology. 2000 Jun 13;54(11):2108–2114. doi: 10.1212/wnl.54.11.2108. [DOI] [PubMed] [Google Scholar]
  36. Tanabe J. L., Amend D., Schuff N., DiSclafani V., Ezekiel F., Norman D., Fein G., Weiner M. W. Tissue segmentation of the brain in Alzheimer disease. AJNR Am J Neuroradiol. 1997 Jan;18(1):115–123. [PMC free article] [PubMed] [Google Scholar]
  37. Tsiskaridze A., Shakarishvili R., Janelidze M., Vashadze T., Chikhladze M. Cognitive correlates of leukoaraiosis in the early stages of Alzheimer's disease. Funct Neurol. 1998 Jan-Mar;13(1):17–25. [PubMed] [Google Scholar]
  38. Yamauchi H., Fukuyama H., Shio H. Corpus callosum atrophy in patients with leukoaraiosis may indicate global cognitive impairment. Stroke. 2000 Jul;31(7):1515–1520. doi: 10.1161/01.str.31.7.1515. [DOI] [PubMed] [Google Scholar]
  39. de Groot J. C., de Leeuw F. E., Oudkerk M., van Gijn J., Hofman A., Jolles J., Breteler M. M. Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol. 2000 Feb;47(2):145–151. doi: 10.1002/1531-8249(200002)47:2<145::aid-ana3>3.3.co;2-g. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES