Pathological correlates of white matter hyperintensities on magnetic resonance imaging

Dementia and Geriatric Cognitive Disorders

Volumn 39, Issue , 2015, Pages 92-104

  Shim, Yong Soo ^a   Yang, Dong Won ^a   Roe, Catherine M ^b   Coats, Mary A ^b   Benzinger, Tammie L ^b   Xiong, Chengjie ^b   Galvin, James E ^c,d,e   Cairns, Nigel J ^b   Morris, John C ^b  

^a The Catholic University of Korea College of Medicine   (South Korea)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Departments of Neurology Medicine   (United States)

^d Departments of Psychiatry and Behavioral Sciences   (United States)

^e NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Dementia; Leukoaraiosis; Neuropathology; Small vessel disease

Indexed keywords

AGED; ALZHEIMER DISEASE; ARTERIOLOSCLEROSIS; ARTERIOSCLEROSIS; ARTICLE; BLOOD VESSEL WALL; BRAIN ATROPHY; BRAIN BLOOD VESSEL; BRAIN HEMORRHAGE; BRAIN SIZE; CEREBROVASCULAR DISEASE; CONTROLLED STUDY; FEMALE; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; LONGITUDINAL STUDY; MAJOR CLINICAL STUDY; MALE; NEUROIMAGING; NEUROPATHOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; VASCULAR AMYLOIDOSIS; WHITE MATTER; WHITE MATTER HYPERINTENSITY; WHITE MATTER LESION; CASE CONTROL STUDY; IMMUNOHISTOCHEMISTRY; PATHOLOGY; SOUTH KOREA; ULTRASTRUCTURE; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; CASE-CONTROL STUDIES; CEREBROVASCULAR DISORDERS; FEMALE; HUMANS; IMMUNOHISTOCHEMISTRY; LONGITUDINAL STUDIES; MAGNETIC RESONANCE IMAGING; MALE; REPUBLIC OF KOREA; WHITE MATTER;

EID: 84961290507     PISSN: 14208008     EISSN: 14219824     Source Type: Journal    
DOI: 10.1159/000366411     Document Type: Article

References (77)

1. Murray AD, Staff RT, Shenkin SD, Deary IJ, Starr JM, Whalley LJ: Brain white matter hyperintensities: relative importance of vascular risk factors in nondemented elderly people. Radiology 2005; 237: 251-257.
2. de Groot JC, de Leeuw FE, Oudkerk M, van Gijn J, Hofman A, Jolles J, Breteler MM: Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol 2000; 47: 145-151.
3. OBrien JT, Wiseman R, Burton EJ, Barber B, Wesnes K, Saxby B, Ford GA: Cognitive associations of subcortical white matter lesions in older people. Ann NY Acad Sci 2002; 977: 436-444.
4. Schmidt R, Ropele S, Enzinger C, Petrovic K, Smith S, Schmidt H, Matthews PM, Fazekas F: White matter lesion progression, brain atrophy, and cognitive decline: the Austrian stroke prevention study. Ann Neurol 2005; 58: 610-616.
5. van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T, Crisby M, Waldemar G, Schmidt R, Fazekas F, Scheltens P: Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke 2005; 36: 2116-2120.
6. Stout JC, Jernigan TL, Archibald SL, Salmon DP: Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type. Arch Neurol 1996; 53: 742-749.
7. Hirono N, Kitagaki H, Kazui H, Hashimoto M, Mori E: Impact of white matter changes on clinical manifestation of Alzheimers disease: a quantitative study. Stroke 2000; 31: 2182-2188.
8. Mungas D, Jagust WJ, Reed BR, Kramer JH, Weiner MW, Schuff N, Norman D, Mack WJ, Willis L, Chui HC: MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimers disease. Neurology 2001; 57: 2229-2235.
9. Scheltens P, Barkhof F, Valk J, Algra PR, van der Hoop RG, Nauta J, Wolters EC: White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimers disease. Evidence for heterogeneity. Brain 1992; 115: 735-748.
10. Schmidt R, Schmidt H, Haybaeck J, Loitfelder M, Weis S, Cavalieri M, Seiler S, Enzinger C, Ropele S, Erkinjuntti T, Pantoni L, Scheltens P, Fazekas F, Jellinger K: Heterogeneity in age-related white matter changes. Acta Neuropathol 2011; 122: 171-185.
11. Fazekas F, Niederkorn K, Schmidt R, Offenbacher H, Horner S, Bertha G, Lechner H: White matter abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors. Stroke 1988; 19: 1285-1288.
12. Lazarus R, Prettyman R, Cherryman G: White matter lesions on magnetic resonance imaging and their relationship with vascular risk factors in memory clinic attenders. Int J Geriatr Psychiatry 2005; 20: 274-279.
13. Lechner H, Schmidt R, Bertha G, Justich E, Offenbacher H, Schneider G: Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals. Stroke 1988; 19: 263-265.
14. Pantoni L, Garcia JH: Pathogenesis of leukoaraiosis. Stroke 1997; 28: 652-659.
15. Simpson JE, Fernando MS, Clark L, Ince PG, Matthews F, Forster G, OBrien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Lewis CE, Wharton SB; MRC Cognitive Function and Ageing Neuropathology Study Group: White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol Appl Neurobiol 2007; 33: 410-419.
16. Sze G, De Armond S, Brant-Zawadzki M, Davis RL, Norman D, Newton TH: Foci of MRI signal (pseudo lesions) anterior to the frontal horns: histologic correlations of a normal finding. AJR Am J Roentgenol 1986; 147: 331-337.
17. Scheltens P, Barkhof F, Leys D, Wolters EC, Ravid R, Kamphorst W: Histopathologic correlates of white matter changes on MRI in Alzheimers disease and normal aging. Neurology 1995; 45: 883-888.
18. Rennels ML, Blaumanis OR, Grady PA: Rapid solute transport throughout the brain via paravascular fluid pathways. Adv Neurol 1990; 52: 431-439.
19. Munoz DG, Hastak SM, Harper B, Lee D, Hachinski VC: Pathologic correlates of increased signals of the centrum ovale on magnetic resonance imaging. Arch Neurol 1993; 50: 492-497.
20. Simpson JE, Ince PG, Higham CE, Gelsthorpe CH, Fernando MS, Matthews F, Forster G, OBrien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Stoeber K, Williams GH, Lewis CE, Wharton SB; MRC Cognitive Function and Ageing Neuropathology Study Group: Microglial activation in white matter lesions and nonlesional white matter of ageing brains. Neuropathol Appl Neurobiol 2007; 33: 670-683.
21. Simpson JE, Fernando MS, Clark L, Ince PG, Matthews F, Forster G, OBrien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Lewis CE, Wharton SB; MRC Cognitive Function and Ageing Neuropathology Study Group: White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol Appl Neurobiol 2007; 33: 410-419.
22. Awad IA, Johnson PC, Spetzler RF, Hodak JA: Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlations. Stroke 1986; 17: 1090-1097.
23. Braffman BH, Zimmerman RA, Trojanowski JQ, Gonatas NK, Hickey WF, Schlaepfer WW: Brain MR: pathologic correlation with gross and histopathology. 2. Hyperintense white-matter foci in the elderly. AJR Am J Roentgenol 1988; 151: 559-566.
24. Berg L, McKeel DW Jr, Miller JP, Storandt M, Rubin EH, Morris JC, Baty J, Coats M, Norton J, Goate AM, Price JL, Gearing M, Mirra SS, Saunders AM: Clinicopathologic studies in cognitively healthy aging and Alzheimers disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol 1998; 55: 326-335.
25. Probstfield JL, Applegate WB, Borhani NO, Curb JD, Cutler JA, Davis BR, Furberg CD, Hawkins CM, Lakatos E, Page LB, Perry HM, Schron E, Smith WM: The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group. Clin Exp Hypertens A 1989; 11: 973-989.
26. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimers disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimers Disease. Neurology 1984; 34: 939-944.
27. Price JL, McKeel DW Jr, Buckles VD, Roe CM, Xiong C, Grundman M, Hansen LA, Petersen RC, Parisi JE, Dickson DW, Smith CD, Davis DG, Schmitt FA, Markesbery WR, Kaye J, Kurlan R, Hulette C, Kurland BF, Higdon R, Kukull W, Morris JC: Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease. Neurobiol Aging 2009; 30: 1026-1036.
28. Braak H, Braak E: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82: 239-259.
29. Mirra SS, Hart MN, Terry RD: Making the diagnosis of Alzheimers disease: a primer for practicing pathologists. Arch Pathol Lab Med 1993; 117: 132-144.
30. Hyman BT, Trojanowski JQ: Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 1997; 56: 1095-1097.
31. Beekly DL, Ramos EM, van Belle G, Deitrich W, Clark AD, Jacka ME, Kukull WA; NIA-Alzheimers Disease Centers: The National Alzheimers Coordinating Center (NACC) Database: an Alzheimer disease database. Alzheimer Dis Assoc Disord 2004; 18: 270-277.
32. Roman GC: Senile dementia of the Binswanger type. A vascular form of dementia in the elderly. JAMA 1987; 258: 1782-1788.
33. Caplan LR: Binswangers disease-revisited. Neurology 1995; 45: 626-633.
34. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA: MR signal abnormalities at 1.5 T in Alzheimers dementia and normal aging. AJR Am J Roentgenol 1987; 149: 351-356.
35. Goulding JM, Signorini DF, Chatterjee S, Nicoll JA, Stewart J, Morris R, Lammie GA: Inverse relation between Braak NFT stage and cerebrovascular pathology in Alzheimer predominant dementia. J Neurol Neurosurg Psychiatry 1999; 67: 654-657.
36. Nagy Z, Esiri MM, Jobst KA, Morris JH, King EM, McDonald B, Joachim C, Litchfield S, Barnetson L, Smith AD: The effects of additional pathology on the cognitive deficit in Alzheimer disease. J Neuropathol Exp Neurol 1997; 56: 165-170.
37. Englund E, Brun A, Persson B: Correlations between histopathologic white matter changes and proton MR relaxation times in dementia. Alzheimer Dis Assoc Disord 1987; 1: 156-170.
38. Rvsz T, Hawkins CP, du Boulay EP, Barnard RO, McDonald WI: Pathological findings correlated with magnetic resonance imaging in subcortical arteriosclerotic encephalopathy (Binswangers disease). J Neurol Neurosurg Psychiatry 1989; 52: 1337-1344.
39. van Swieten JC, van den Hout JH, van Ketel BA, Hijdra A, Wokke JH, van Gijn J: Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain 1991; 114: 761-774.
40. Marshall VG, Bradley WG Jr, Marshall CE, Bhoopat T, Rhodes RH: Deep white matter infarction: correlation of MR imaging and histopathologic findings. Radiology 1988; 167: 517-522.
41. Fernando MS, Simpson JE, Matthews F, Brayne C, Lewis CE, Barber R, Kalaria RN, Forster G, Esteves F, Wharton SB, Shaw PJ, OBrien JT, Ince PG; MRC Cognitive Function and Ageing Neuropathology Study Group: White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury. Stroke 2006; 37: 1391-1398.
42. Auriel E, Bornstein NM, Berenyi E, Varkonyi I, Gabor M, Majtenyi K, Szepesi R, Goldberg I, Lampe R, Csiba L: Clinical, radiological and pathological correlates of leukoaraiosis. Acta Neurol Scand 2011; 123: 41-47.
43. Auriel E, Csiba L, Berenyi E, Varkonyi I, Mehes G, Kardos L, Karni A, Bornstein NM: Leukoaraiosis is associated with arterial wall thickness: a quantitative analysis. Neuropathology 2012; 32: 227-233.
44. Young VG, Halliday GM, Kril JJ: Neuropathologic correlates of white matter hyperintensities. Neurology 2008; 71: 804-811.
45. Moody DM, Thore CR, Anstrom JA, Challa VR, Langefeld CD, Brown WR: Quantification of afferent vessels shows reduced brain vascular density in subjects with leukoaraiosis. Radiology 2004; 233: 883-890.
46. Brown WR, Moody DM, Challa VR, Thore CR, Anstrom JA: Venous collagenosis and arteriolar tortuosity in leukoaraiosis. J Neurol Sci 2002; 203-204: 159-163.
47. 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; 43: 1683-1639.
48. Brun A, Englund E: A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study. Ann Neurol 1986; 19: 253-262.
49. Munoz DG: Leukoaraiosis and ischemia: beyond the myth. Stroke 2006; 37: 1348-1349.
50. Black S, Gao FQ, Bilbao J: Understanding white matter disease: imaging-pathological correlation in vascular cognitive impairment. Stroke 2009; 40:S48-S52.
51. Morris JC, Gado M, Torack RM, McKeel DW Jr: Binswangers disease or artifact: a clinical, neuroimaging, and pathological study of periventricular white matter changes in Alzheimers disease. Adv Neurol 1990; 51: 47-51.
52. Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjögren M, Wallin A, Ader H, Leys D, Pantoni L, Pasquier F, Erkinjuntti T, Scheltens P; European Task Force on Age-Related White Matter Changes: A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001; 32: 1318-1322.
53. Fazekas F, Kleinert R, Offenbacher H, Payer F, Schmidt R, Kleinert G, Radner H, Lechner H: The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR Am J Neuroradiol 1991; 12: 915-921.
54. Chimowitz MI, Estes ML, Furlan AJ, Awad IA: Further observations on the pathology of subcortical lesions identified on magnetic resonance imaging. Arch Neurol 1992; 49: 747-752.
55. Udaka F, Sawada H, Kameyama M: White matter lesions and dementia: MRI pathological correlation. Ann NY Acad Sci 2002; 977: 411-415.
56. Leifer D, Buonanno FS, Richardson EP Jr: Clinicopathologic correlations of cranial magnetic resonance imaging of periventricular white matter. Neurology 1990; 40: 911-918.
57. Rossi R, Joachim C, Geroldi C, Combrinck M, Esiri MM, Smith AD, Frisoni GB: Association between subcortical vascular disease on CT and neuropathological findings. Int J Geriatr Psychiatry 2004; 19: 690-695.
58. Gouw AA, Seewann A, van der Flier WM, Barkhof F, Rozemuller AM, Scheltens P, Geurts JJG: Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 2011; 82: 126-135.
59. Jagust WJ, Zheng L, Harvey DJ, Mack WJ, Vinters HV, Weiner MW, Ellis WG, Zarow C, Mungas D, Reed BR, Kramer JH, Schuff N, DeCarli C, Chui HC: Neuropathological basis of magnetic resonance images in aging and dementia. Ann Neurol 2008; 63: 72-80.
60. Scarpelli M, Salvolini U, Diamanti L, Montironi R, Chiaromoni L, Maricotti M: MRI and pathological examination of post-mortem brains: the problem of white matter high signal areas. Neuroradiology 1994; 36: 393-398.
61. Smith CD, Snowdon D, Markesbery WR: Periventricular white matter hyperintensities on MRI: correlation with neuropathologic findings. J Neuroimaging 2000; 10: 13-16.
62. Burns JM, Church JA, Johnson DK, Xiong CX, Marcus D, Fotenos AF, Snyder AZ, Morris JC, Buckner RL: White matter lesions are prevalent but differently related with cognition an aging and early Alzheimer disease. Arch Neurol 2005; 62: 1870-1876.
63. 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; 43: 1683-1689.
64. McAleese KE, Firbank M, Hunter D, Sun L, Hall R, Neal JW, Mann DM, Esiri M, Jellinger KA, OBrien JT, Attems J: Magnetic resonance imaging of fixed post mortem brains reliably reflects subcortical vascular pathology of frontal, parietal and occipital white matter. Neuropathol Appl Neurobiol 2013; 39: 485-497.
65. Thal DR, Ghebremedhin E, Orantes M, Wiestler OD: Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 2003; 62: 1287-1301.
66. Beach TG, Wilson JR, Sue LI, Newell A, Poston M, Cisneros R, Pandya Y, Esh C, Connor DJ, Sabbagh M, Walker DG, Roher AE: Circle of Willis atherosclerosis: association with Alzheimers disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathol 2007; 113: 13-21.
67. Honig LS, Kukull W, Mayeux R: Atherosclerosis and AD: analysis of data from the US National Alzheimers Coordinating Center. Neurology 2005; 64: 494-500.
68. Roher AE, Esh C, Rahman A, Kokjohn TA, Beach TG: Atherosclerosis of cerebral arteries in Alzheimer disease. Stroke 2004; 35: 2623-2627.
69. Zekry D, Duyckaerts C, Moulias R, Belmin J, Geoffre C, Herrmann F, Hauw JJ: Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly. Acta Neuropathol 2002; 103: 481-487.
70. Aho L, Jolkkonen J, Alafuzoff I: Beta-amyloid aggregation in human brains with cerebrovascular lesions. Stroke 2006; 37: 2940-2945.
71. Luoto TM, Haikonen S, Haapasalo H, Goebeler S, Huhtala H, Erkinjuntti T, Karhunen PJ: Large vessel cerebral atherosclerosis is not in direct association with neuropathological lesions of Alzheimers disease. Eur Neurol 2009; 62: 93-98.
72. Tomimoto H, Akiguchi I, Suenaga T, Nishimura M, Wakita H, Nakamura S, Kimura J: Alterations of the bloodbrain barrier and glial cells in white-matter lesions in cerebrovascular and Alzheimers disease patients. Stroke 1996; 27: 2069-2074.
73. Haller S, Kövari E, Herrmann FR, Cuvinciuc V, Tomm AM, Zulian GB, Lovblad KO, Giannakopoulos P, Bouras C: Do brain T2/FLAIR white matter hyperintensities correspond to myelin loss in normal aging? A radiologicneuropathologic correlation study. Acta Neuropathol Commun 2013; 1: 14.
74. Simpson JE, Ince PG, Higham CE, Gelsthorpe CH, Fernando MS, Matthews F, Forster G, OBrien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Stoeber K, Williams GH, Lewis CE, Wharton SB; MRC Cognitive Function and Ageing Neuropathology Study Group: Microglial activation in white matter lesions and nonlesional white matter of ageing brains. Neuropathol Appl Neurobiol 2007; 33: 670-683.
75. OSullivan M, Summers PE, Jones DK, Jarosz JM, Williams SC, Markus HS: Normal-appearing white matter in ischemic leukoaraiosis: a diffusion tensor MRI study. Neurology 2001; 57: 2307-2310.
76. Moody DM, Brown WR, Challa VR, Anderson RL: Periventricular venous collagenosis: association with leukoaraiosis. Radiology 1995; 194: 469-476.
77. Moody DM, Brown WR, Challa VR, Ghazi-Birry HS, Reboussin DM: Cerebral microvascular alterations in aging, leukoaraiosis, and Alzheimers disease. Ann NY Acad Sci 1997; 826: 103-116.