Skip to main content
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2005 Sep;76(9):1229–1233. doi: 10.1136/jnnp.2004.055657

White matter hyperintensities as a predictor of neuropsychological deficits post-stroke

H Jokinen 1, H Kalska 1, R Mantyla 1, R Ylikoski 1, M Hietanen 1, T Pohjasvaara 1, M Kaste 1, T Erkinjuntti 1
PMCID: PMC1739804  PMID: 16107356

Abstract

Objectives: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients.

Methods: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses.

Results: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions.

Conclusions: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.

Full Text

The Full Text of this article is available as a PDF (77.9 KB).

Selected References

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

  1. Breteler M. M., van Swieten J. C., Bots M. L., Grobbee D. E., Claus J. J., van den Hout J. H., van Harskamp F., Tanghe H. L., de Jong P. T., van Gijn J. Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology. 1994 Jul;44(7):1246–1252. doi: 10.1212/wnl.44.7.1246. [DOI] [PubMed] [Google Scholar]
  2. Burton Emma J., Kenny Rose Anne, O'Brien John, Stephens Sally, Bradbury Michael, Rowan Elise, Kalaria Raj, Firbank Michael, Wesnes Keith, Ballard Clive. White matter hyperintensities are associated with impairment of memory, attention, and global cognitive performance in older stroke patients. Stroke. 2004 Apr 29;35(6):1270–1275. doi: 10.1161/01.STR.0000126041.99024.86. [DOI] [PubMed] [Google Scholar]
  3. Burton Emma, Ballard Clive, Stephens Sally, Kenny Rose Anne, Kalaria Raj, Barber Robert, O'Brien John. Hyperintensities and fronto-subcortical atrophy on MRI are substrates of mild cognitive deficits after stroke. Dement Geriatr Cogn Disord. 2003;16(2):113–118. doi: 10.1159/000070684. [DOI] [PubMed] [Google Scholar]
  4. Cohen Ronald A., Paul Robert H., Ott Brian R., Moser David J., Zawacki Tricia M., Stone William, Gordon Norman. The relationship of subcortical MRI hyperintensities and brain volume to cognitive function in vascular dementia. J Int Neuropsychol Soc. 2002 Sep;8(6):743–752. doi: 10.1017/s1355617702860027. [DOI] [PubMed] [Google Scholar]
  5. Cook Ian A., Leuchter Andrew F., Morgan Melinda L., Conlee Elise Witte, David Steven, Lufkin Robert, Babaie Ashkan, Dunkin Jennifer J., O'Hara Ruth, Simon Sara. Cognitive and physiologic correlates of subclinical structural brain disease in elderly healthy control subjects. Arch Neurol. 2002 Oct;59(10):1612–1620. doi: 10.1001/archneur.59.10.1612. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Fukui T., Sugita K., Sato Y., Takeuchi T., Tsukagoshi H. Cognitive functions in subjects with incidental cerebral hyperintensities. Eur Neurol. 1994;34(5):272–276. doi: 10.1159/000117055. [DOI] [PubMed] [Google Scholar]
  9. Garde E., Mortensen E. L., Krabbe K., Rostrup E., Larsson H. B. Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study. Lancet. 2000 Aug 19;356(9230):628–634. doi: 10.1016/S0140-6736(00)02604-0. [DOI] [PubMed] [Google Scholar]
  10. Jokinen H., Kalska H., Ylikoski R., Hietanen M., Mäntylä R., Pohjasvaara T., Kaste M., Erkinjuntti T. Medial temporal lobe atrophy and memory deficits in elderly stroke patients. Eur J Neurol. 2004 Dec;11(12):825–832. doi: 10.1111/j.1468-1331.2004.00870.x. [DOI] [PubMed] [Google Scholar]
  11. Junqué C., Pujol J., Vendrell P., Bruna O., Jódar M., Ribas J. C., Viñas J., Capdevila A., Marti-Vilalta J. L. Leuko-araiosis on magnetic resonance imaging and speed of mental processing. Arch Neurol. 1990 Feb;47(2):151–156. doi: 10.1001/archneur.1990.00530020047013. [DOI] [PubMed] [Google Scholar]
  12. Leskelä M., Hietanen M., Kalska H., Ylikoski R., Pohjasvaara T., Mäntylä R., Erkinjuntti T. Executive functions and speed of mental processing in elderly patients with frontal or nonfrontal ischemic stroke. Eur J Neurol. 1999 Nov;6(6):653–661. doi: 10.1046/j.1468-1331.1999.660653.x. [DOI] [PubMed] [Google Scholar]
  13. Libon D. J., Bogdanoff B., Leopold N., Hurka R., Bonavita J., Skalina S., Swenson R., Gitlin H. L., Ball S. K. Neuropsychological profiles associated with subcortical white matter alterations and Parkinson's disease: implications for the diagnosis of dementia. Arch Clin Neuropsychol. 2001 Jan;16(1):19–32. [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Mungas D., Jagust W. J., Reed B. R., Kramer J. H., Weiner M. W., Schuff N., Norman D., Mack W. J., Willis L., Chui H. C. MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer's disease. Neurology. 2001 Dec 26;57(12):2229–2235. doi: 10.1212/wnl.57.12.2229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mäntylä R., Erkinjuntti T., Salonen O., Aronen H. J., Peltonen T., Pohjasvaara T., Standertskjöld-Nordenstam C. G. Variable agreement between visual rating scales for white matter hyperintensities on MRI. Comparison of 13 rating scales in a poststroke cohort. Stroke. 1997 Aug;28(8):1614–1623. doi: 10.1161/01.str.28.8.1614. [DOI] [PubMed] [Google Scholar]
  18. Nelson H. E. A modified card sorting test sensitive to frontal lobe defects. Cortex. 1976 Dec;12(4):313–324. doi: 10.1016/s0010-9452(76)80035-4. [DOI] [PubMed] [Google Scholar]
  19. O'Brien John T., Erkinjuntti Timo, Reisberg Barry, Roman Gustavo, Sawada Tohru, Pantoni Leonardo, Bowler John V., Ballard Clive, DeCarli Charles, Gorelick Philip B. Vascular cognitive impairment. Lancet Neurol. 2003 Feb;2(2):89–98. doi: 10.1016/s1474-4422(03)00305-3. [DOI] [PubMed] [Google Scholar]
  20. O'Sullivan M., Jones D. K., Summers P. E., Morris R. G., Williams S. C., Markus H. S. Evidence for cortical "disconnection" as a mechanism of age-related cognitive decline. Neurology. 2001 Aug 28;57(4):632–638. doi: 10.1212/wnl.57.4.632. [DOI] [PubMed] [Google Scholar]
  21. Perret E. The left frontal lobe of man and the suppression of habitual responses in verbal categorical behaviour. Neuropsychologia. 1974 Jul;12(3):323–330. doi: 10.1016/0028-3932(74)90047-5. [DOI] [PubMed] [Google Scholar]
  22. Pohjasvaara T., Erkinjuntti T., Vataja R., Kaste M. Dementia three months after stroke. Baseline frequency and effect of different definitions of dementia in the Helsinki Stroke Aging Memory Study (SAM) cohort. Stroke. 1997 Apr;28(4):785–792. doi: 10.1161/01.str.28.4.785. [DOI] [PubMed] [Google Scholar]
  23. Pohjasvaara T., Mäntylä R., Salonen O., Aronen H. J., Ylikoski R., Hietanen M., Kaste M., Erkinjuntti T. How complex interactions of ischemic brain infarcts, white matter lesions, and atrophy relate to poststroke dementia. Arch Neurol. 2000 Sep;57(9):1295–1300. doi: 10.1001/archneur.57.9.1295. [DOI] [PubMed] [Google Scholar]
  24. Pugh Kenneth G., Lipsitz Lewis A. The microvascular frontal-subcortical syndrome of aging. Neurobiol Aging. 2002 May-Jun;23(3):421–431. doi: 10.1016/s0197-4580(01)00319-0. [DOI] [PubMed] [Google Scholar]
  25. Sachdev P. S., Brodaty H., Valenzuela M. J., Lorentz L., Looi J. C. L., Wen W., Zagami A. S. The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients. Neurology. 2004 Mar 23;62(6):912–919. doi: 10.1212/01.wnl.0000115108.65264.4b. [DOI] [PubMed] [Google Scholar]
  26. Stuss Donald T., Levine Brian. Adult clinical neuropsychology: lessons from studies of the frontal lobes. Annu Rev Psychol. 2002;53:401–433. doi: 10.1146/annurev.psych.53.100901.135220. [DOI] [PubMed] [Google Scholar]
  27. Tekin Sibel, Cummings Jeffrey L. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res. 2002 Aug;53(2):647–654. doi: 10.1016/s0022-3999(02)00428-2. [DOI] [PubMed] [Google Scholar]
  28. Tullberg M., Fletcher E., DeCarli C., Mungas D., Reed B. R., Harvey D. J., Weiner M. W., Chui H. C., Jagust W. J. White matter lesions impair frontal lobe function regardless of their location. Neurology. 2004 Jul 27;63(2):246–253. doi: 10.1212/01.wnl.0000130530.55104.b5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Vataja R., Pohjasvaara T., Mäntylä R., Ylikoski R., Leppävuori A., Leskelä M., Kalska H., Hietanen M., Aronen H. J., Salonen O. MRI correlates of executive dysfunction in patients with ischaemic stroke. Eur J Neurol. 2003 Nov;10(6):625–631. doi: 10.1046/j.1468-1331.2003.00676.x. [DOI] [PubMed] [Google Scholar]
  30. Wu C. C., Mungas D., Petkov C. I., Eberling J. L., Zrelak P. A., Buonocore M. H., Brunberg J. A., Haan M. N., Jagust W. J. Brain structure and cognition in a community sample of elderly Latinos. Neurology. 2002 Aug 13;59(3):383–391. doi: 10.1212/wnl.59.3.383. [DOI] [PubMed] [Google Scholar]
  31. Ylikoski R., Ylikoski A., Erkinjuntti T., Sulkava R., Raininko R., Tilvis R. White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol. 1993 Aug;50(8):818–824. doi: 10.1001/archneur.1993.00540080029009. [DOI] [PubMed] [Google Scholar]
  32. 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