Cognitive correlates of cerebral white matter changes

  • J. C. de Groot
  • F. E. de Leeuw
  • M. M. B. Breteler
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 53)


The introduction of computer tomography (CT) and magnetic resonance imaging (MRI) has revealed unexpected cerebral findings of unknown consequences. Changes in the white matter of the brain appear in both normal and cognitively impaired elderly individuals and are common in demented patients. White matter changes are known under a variety of synonyms. On MRI they are also termed white matter lesions, hyperintensities, foci, findings or unidentified bright objects and on CT white matter lucencies or leukoaraiosis.


White Matter White Matter Lesion White Matter Change Verbal Fluency Task Subjective Memory Complaint 
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.


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  1. Almkvist O, Wahlund LO, Andersson-Lundman G, Basun H, Backman L (1992) White-matter hyperintensity and neuropsychological functions in dementia and healthy aging. Arch Neurol 49: 626–632PubMedCrossRefGoogle Scholar
  2. Amar K, Lewis T, Wilcock G, Scott M, Bucks R (1995) The relationship between white matter low attenuation on brain CT and vascular risk factors: a memory clinic study. Age Ageing 24: 411–415PubMedCrossRefGoogle Scholar
  3. Awad IA, Johnson PC, Spetzler RF, Hodak JA (1986) Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlations. Stroke 17: 1090–1097PubMedCrossRefGoogle Scholar
  4. Aylward EH, Roberts-Twillie JV, Barta PE, Kumar AJ, Harris GJ, Geer M, Peyser CE, Pearlson GD (1994) Basal ganglia volumes and white matter hyperintensities in patients with bipolar disorder. Am J Psychiatry 151: 687–693PubMedGoogle Scholar
  5. Baloh RW, Vinters HV (1995) White matter lesions and disequilibrium in older people. II. Clinicopathologic correlation. Arch Neurol 52: 975–981PubMedCrossRefGoogle Scholar
  6. Bandura A (1989) Regulation of cognitive processes through perceived self-efficacy. Dev Psychol 25: 729–735CrossRefGoogle Scholar
  7. Baum KA, Schulte C, Girke W, Reischies FM, Felix R (1996) Incidental white-matter foci on MRI in “healthy” subjects: evidence of subtle cognitive dysfunction. Neuroradiology 38: 755–760PubMedCrossRefGoogle Scholar
  8. Binetti G, Padovani A, Magni E, Bianchetti A, Scuratti A, Lenzi GL, Trabucchi M (1995) Delusions and dementia: clinical and CT correlates. Acta Neurol Scandi 91: 271–275CrossRefGoogle Scholar
  9. Blennow K, Wallin A, Uhlemann C, Gottfries CG (1991) White-matter lesions on CT in Alzheimer patients: relation to clinical symptomatology and vascular factors. Acta Neurol Scand 83: 187–193PubMedCrossRefGoogle Scholar
  10. Blessed G, Tomlinson BE, Roth M (1968) The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 114: 797–811PubMedCrossRefGoogle Scholar
  11. Boone KB, Miller BL, Lesser IM, Mehringer CM, Hill-Gutierrez E, Goldberg MA, Berman NG (1992) Neuropsychological correlates of white-matter lesions in healthy elderly subjects. A threshold effect. Arch Neurol 49: 549–554CrossRefGoogle Scholar
  12. Brand N, Jolies J (1987) Information processing in depression and anxiety. Psychol Med 17: 145–153PubMedCrossRefGoogle Scholar
  13. Breteler MM, van Amerongen NM, van Swieten JC, Claus JJ, Grobbee DE, van Gijn J, Hofman A, van Harskamp F (1994) Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study. Stroke 25: 1109–1115CrossRefGoogle Scholar
  14. Brown FW (1993) The neurobiology of late-life psychosis. [Review]. Crit Rev Neurobiol 7: 275–289PubMedGoogle Scholar
  15. Cavanaugh JC, Green EE (1990) I believe, therefore I can: Self-efficacy beliefs in memory aging. [References.] In: Lovelace EA (ed) North-Holland, Amsterdam, pp 189–230Google Scholar
  16. Challa VR, Moody DM (1987) White-matter lesions in MR imaging of elderly subjects. [Letter.] Radiology 164: 874–875PubMedGoogle Scholar
  17. Cummings JL (1986) Subcortical dementia. Neuropsychology, neuropsychiatry, and pathophysiology. [Review.] Br J Psychiatry 149: 682–697PubMedCrossRefGoogle Scholar
  18. Cummings JL, Benson DF (1988) Psychological dysfunction accompanying subcortical dementias. [Review.] Ann Rev Med 39: 53–61PubMedCrossRefGoogle Scholar
  19. de la Monte SM (1989) Quantitation of cerebral atrophy in preclinical and end-stage Alzheimer’s disease. Ann Neurol 25: 450–459PubMedCrossRefGoogle Scholar
  20. DeCarli C, Murphy DG, Tranh M, Grady CL, Haxby JV, Gillette JA, Salerno JA, Gonzales-Aviles A, Horwitz B, Rapoport SI, et al (1995) The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology 45: 2077–2084CrossRefGoogle Scholar
  21. Derix MAA (1994) Neuropsychological differentiation of dementia syndromes. Lisse, Swets en ZeitlingerGoogle Scholar
  22. Diaz JF, Merskey H, Hachinski VC, Lee DH, Boniferro M, Wong CJ, Mirsen TR, Fox H (1991) Improved recognition of leukoaraiosis and cognitive impairment in Alzheimer’s disease. Arch Neurol 48: 1022–1025PubMedCrossRefGoogle Scholar
  23. Dixon RA, Hultsch DF, Hertzog C (1988) The metamemory in adulthood (MIA) questionnaire [published erratum appears in Psychopharmacol Bull (1989) 25: 157]. Psychopharmacol Bull 24: 671–688PubMedGoogle Scholar
  24. Dupont RM, Jernigan TL, Heindel W, Butters N, Shafer K, Wilson T, Hesselink J, Gillin JC (1995) Magnetic resonance imaging and mood disorders. Localization of white matter and other subcortical abnormalities. Arch Gen Psychiatry 52: 747–755PubMedCrossRefGoogle Scholar
  25. Erkinjuntti T, Ketonen L, Sulkava R, Sipponen J, Vuorialho M, Iivanainen M (1987) Do white matter changes on MRI and CT differentiate vascular dementia from Alzheimer’s disease? J Neurol Neurosurg Psychiatry 50: 37–42PubMedCrossRefGoogle Scholar
  26. Fazekas F, Kleinert R, Offenbacher H, Schmidt R, Kleinert G, Payer F, Radner H, Lechner H (1993) Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 43: 1683–1689PubMedCrossRefGoogle Scholar
  27. Fein G, Van Dyke C, Davenport L, Turetsky B, Brant-Zawadzki M, Zatz L, Dillon W, Valk P (1990) Preservation of normal cognitive functioning in elderly subjects with extensive white-matter lesions of long duration. Arch Gen Psychiatry 47: 220–223PubMedCrossRefGoogle Scholar
  28. Figiel GS, Krishnan KR, Rao VP, Doraiswamy M, Ellinwood E, Jr, Nemeroff CB, Evans D, Boyko O (1991) Subcortical hyperintensities on brain magnetic resonance imaging: a comparison of normal and bipolar subjects. J Neuropsychiatr Clin Neurosci 3: 18–22Google Scholar
  29. Fischer P, Gatterer G, Marterer A, Danielczyk W (1988) Nonspecificity of semantic impairment in dementia of Alzheimer’s type. Arch Neurol 45: 1341–1343PubMedCrossRefGoogle Scholar
  30. 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: 189–198PubMedCrossRefGoogle Scholar
  31. Fukui T, Sugita K, Sato Y, Takeuchi T, Tsukagoshi H (1994) Cognitive functions in subjects with incidental cerebral hyperintensities. Eur Neurol 34: 272–276PubMedCrossRefGoogle Scholar
  32. Gawnecain ML, Silver NC, Moseley IF, Miller DH (1997) Fast FLAIR of the brain: the range of appearances in normal subjects and its application to quantification of white-matter disease. Neuroradiology 39: 243–249CrossRefGoogle Scholar
  33. Hachinski VC, Potter P, Merskey H (1987) Leuko-araiosis. Arch Neurol 44: 21–23PubMedCrossRefGoogle Scholar
  34. Harrell LE, Duvall E, Folks DG, Duke L, Bartolucci A, Conboy T, Callaway R, Kerns D (1991) The relationship of high-intensity signals on magnetic resonance images to cognitive and psychiatric state in Alzheimer’s disease. Arch Neurol 48: 1136–1140PubMedCrossRefGoogle Scholar
  35. Hersch EL (1979) Development and application of the extended scale for dementia. J Am Geriatr Soc 27: 348–354PubMedGoogle Scholar
  36. Houx PJ, Jolies J, Vreeling FW (1993) Stroop interference: aging effects assessed with the Stroop Color-Word Test. Exp Aging Res 19: 209–224PubMedCrossRefGoogle Scholar
  37. Hunt AL, Orrison WW, Yeo RA, Haaland KY, Rhyne RL, Garry PJ, Rosenberg GA (1989) Clinical significance of MRI white matter lesions in the elderly [see comments]. Neurology 39: 1470–1474PubMedCrossRefGoogle Scholar
  38. Johnson KA, Davis KR, Buonanno FS, Brady TJ, Rosen TJ, Growdon JH (1987) Comparison of magnetic resonance and roentgen ray computed tomography in dementia. Arch Neurol 44: 1075–1080PubMedCrossRefGoogle Scholar
  39. Junque C, Pujol J, Vendrell P, Bruna O, Jodar M, Ribas JC, Vinas J, Capdevila A, Marti-Vilalta JL (1990) Leuko-araiosis on magnetic resonance imaging and speed of mental processing. Arch Neurol 47: 151–156PubMedCrossRefGoogle Scholar
  40. 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
  41. Leys D, Soetaert G, Petit H, Fauquette A, Pruvo JP, Steinling M (1990) Periventricular and white matter magnetic resonance imaging hyperintensities do not differ between Alzheimer’s disease and normal aging [see comments]. Arch Neurol 47: 524–527PubMedCrossRefGoogle Scholar
  42. Lezak MD (1995) Neuropsychological assesment. Oxford University Press, New YorkGoogle Scholar
  43. Liao DP, Cooper L, Cai JW, Toole JF, Bryan NR, Hutchinson RG, Tyroler HA (1996) Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control: the ARIC study. Stroke 27: 2262–2270PubMedCrossRefGoogle Scholar
  44. Longstreth W, Jr, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, Enright PL, O’Leary D, Fried L (1996) Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study [see comments]. Stroke 27: 1274–1282Google Scholar
  45. Lopez OL, Becker JT, Rezek D, Wess J, Boiler F, Reynolds CD, Panisset M (1992) Neuropsychiatric correlates of cerebral white-matter radiolucencies in probable Alzheimer’s disease. Arch Neurol 49: 828–834PubMedCrossRefGoogle Scholar
  46. Lovelace A (1990) Aging and cognition: mental processes, self-awareness, and interventions. North Holland, Amsterdam, 452: 15Google Scholar
  47. Lovelace EA (1990) Aging and metacognitions concerning memory function. [References.] In: Lovelace EA (ed) Aging and cognition. North-Holland, Amsterdam, pp 157–188Google Scholar
  48. Malloy PF, Cummings JL, Coffey CE, Duffy J, Fink M, Lauterbach EC, Lovell M, Royall D, Salloway S (1997) Cognitive screening instruments in neuropsychiatry: a report of the committee on research of the American Neuropsychiatric Association. J Neuropsychiatr Clin Neurosci 9: 189–197Google Scholar
  49. Matsubayashi K, Shimada K, Kawamoto A, Ozawa T (1992) Incidental brain lesions on magnetic resonance imaging and neurobehavioral functions in the apparently healthy elderly. Stroke 23: 175–180PubMedCrossRefGoogle Scholar
  50. McDonald WM, Krishnan KR, Doraiswamy PM, Blazer DG (1991) Occurrence of sub-cortical hyperintensities in elderly subjects with mania. Psychiatr Res 40: 211–220CrossRefGoogle Scholar
  51. Mirsen TR, Lee DH, Wong CJ, Diaz JF, Fox AJ, Hachinski VC, Merskey H (1991) Clinical correlates of white-matter changes on magnetic resonance imaging scans of the brain. Arch Neurol 48: 1015–1021PubMedCrossRefGoogle Scholar
  52. Pollman S, Haupt M, Kurz A (1995) Changes of the relative severity of naming, fluency and recall impairment in the course of dementia of the Alzheimer type. Dementia 6: 252–257PubMedGoogle Scholar
  53. Ponds RW, Jolies J (1996) The Abridged Dutch Metamemory in Adulthood (MIA) Questionnaire: structure and effects of age, sex, and education. Psychol Aging 11: 324–332PubMedCrossRefGoogle Scholar
  54. Radloff LS (1977) The CES-D Scale: a self-report depression scale for research in the general population. Appl Psychol Measurem 1: 385–401CrossRefGoogle Scholar
  55. Rao SM, Mittenberg W, Bernardin L, Haughton V, Leo GJ (1989) Neuropsychological test findings in subjects with leukoaraiosis. Arch Neurol 46: 40–44PubMedCrossRefGoogle Scholar
  56. Reitan RM (1958) Validity of trail making test as an indicator of organic brain damage. Percept Mot Skills 8: 271–276Google Scholar
  57. 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
  58. Salloway S, Malloy P, Kohn R, Gillard E, Duffy J, Rogg J, Tung G, Richardson E, Thomas C, Westlake R (1996) MRI and neuropsychological differences in early-and late-life-onset geriatric depression. Neurology 46: 1567–1574PubMedCrossRefGoogle Scholar
  59. 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
  60. Scheltens P, Barkhof F, Valk J, Algra PR, van der Hoop RG, Nauta J, Wolters EC (1992) White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer’s disease. Evidence for heterogeneity. Brain 115: 735–748CrossRefGoogle Scholar
  61. Schmidt R, Fazekas F, Offenbacher H, Lytwyn H, Blematl B, Niederkorn K, Horner S, Payer F, Freidl W (1991) Magnetic resonance imaging white matter lesions and cognitive impairment in hypertensive individuals. Arch Neurol 48: 417–420PubMedCrossRefGoogle Scholar
  62. Schmidt R, Fazekas F, Offenbacher H, Dusek T, Zach E, Reinhart B, Grieshofer P, Freidl W, Eber B, Schumacher M, et al (1993) Neuropsychologic correlates of MRI white matter hyperintensities: a study of 150 normal volunteers. Neurology 43: 2490–2494PubMedCrossRefGoogle Scholar
  63. Schofield PW, Marder M, Dooneief G, Jacobs DM, Sano M, Stern Y (1997) Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment. Am J Psychiatry 154: 609–615PubMedGoogle Scholar
  64. Skoog I, Berg S, Johansson B, Palmertz B, Andreasson LA (1996) The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year-olds. Acta Neurol Scand 93: 142–148PubMedCrossRefGoogle Scholar
  65. Smith A (1968) The Symbol Digit Modalities Test: a neuropsychological test for economic screening of learning and other cerebral disorders. Learn Disord 3: 83–91Google Scholar
  66. Steingart A, Hachinski VC, Lau C, Fox AJ, Diaz F, Cape R, Lee D, Inzitari D, Merskey H (1987) Cognitive and neurologic findings in subjects with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis). Arch Neurol 44: 32–35PubMedCrossRefGoogle Scholar
  67. Steingart A, Hachinski VC, Lau C, Fox AJ, Fox H, Lee D, Inzitari D, Merskey H (1987) Cognitive and neurologic findings in demented patients with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis). Arch Neurol 44: 36–39PubMedCrossRefGoogle Scholar
  68. Sternberg S (1975) Memory scanning: new findings and current controversies. Quart J Exp Psychol 27: 1–32CrossRefGoogle Scholar
  69. Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18: 643–662CrossRefGoogle Scholar
  70. Sze G, De Armond SJ, Brant-Zawadzki M, Davis RL, Norman D, Newton TH (1986) Foci of MRI signal (pseudo lesions) anterior to the frontal horns: histologic correlations of a normal finding. Am J Roentgenol 147: 331–337CrossRefGoogle Scholar
  71. Teng EL, Chui HC (1987) The Modified Mini-Mental State (3MS) examination. J Clin Psychiatr 48: 314–318Google Scholar
  72. Tiffin J (1948) SRA Examiner’s Manual for the Purdue Pegboard. Science Research Associate, Inc., Chicago, 111Google Scholar
  73. Tupler LA, Coffey CE, Logue PE, Djang WT, Fagan SM (1992) Neuropsychological importance of subcortical white matter hyperintensity. [Review.] Arch Neurol 49: 1248–1252PubMedCrossRefGoogle Scholar
  74. van Swieten JC, Hijdra A, Koudstaal PJ, van Gijn J (1990) Grading white matter lesions on CT and MRI: a simple scale. J Neurol Neurosurg Psychiatry 53: 1080–1083PubMedCrossRefGoogle Scholar
  75. van Swieten JC, Geyskes GG, Derix MM, Peeck BM, Ramos LM, van Latum JC, van Gijn J (1991) Hypertension in the elderly is associated with white matter lesions and cognitive decline. Ann Neurol 30: 825–830PubMedCrossRefGoogle Scholar
  76. Vega A (1969) Use of Purdue pegboard and finger tapping performance as a rapid screening test for brain damage. J Clin Psychol 25: 255–258PubMedCrossRefGoogle Scholar
  77. Wahlund LO (1996) Magnetic resonance imaging and computed tomography in Alzheimer’s disease. Acta Neurol Scand [Suppl] 168: 50–53CrossRefGoogle Scholar
  78. Wahlund LO, Basun H, Almkvist O, Andersson-Lundman G, Julin P, Saaf J (1994) White matter hyperintensities in dementia: does it matter? Magn Reson Imag 12: 387–394CrossRefGoogle Scholar
  79. Wechsler DA (1945) A standardized memory scale for clinical use. J Psychol 19: 87–95CrossRefGoogle Scholar
  80. Wechsler DA (1955) The Wechsler adult intelligence scale: manual. Psychological Corporation, New YorkGoogle Scholar
  81. Ylikoski R, Ylikoski A, Erkinjuntti T, Sulkava R, Raininko R, Tilvis R (1993) White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol 50: 818–824PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • J. C. de Groot
    • 1
  • F. E. de Leeuw
    • 1
  • M. M. B. Breteler
    • 1
  1. 1.Department of Epidemiology and BiostatisticsErasmus University Medical SchoolRotterdamThe Netherlands

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