Neuropathology of white matter changes in Alzheimer’s disease and vascular dementia
Abstract
Morphological white matter changes were investigated in clinically and neuropathologically diagnosed cases of Alzheimer's disease (AD; 60 cases) and vascular dementia (VaD; 40 cases). In 33 of 60 AD cases, a white matter disease (WMD) characterized by tissue rarefaction, mild gliosis and a non-amyloid small-vessel sclerosis occurred in the central, preferentially frontal deep white matter. The mean vessel density was significantly lower than in normal control case frontal white matter. The presence of WMD did not parallel the severity of grey matter Alzheimer encephalopathy. In 25 of 60 AD cases, white matter degeneration with signs of both condensation and rarefaction of tissue elements was seen subjacent to advanced cortical degeneration in the temporal lobes. It concurred with WMD in only 13 cases and was judged to be of anterograde, Wallerian type and not related to angiopathy. In VaD, similar changes occurred, accompanied by several types of focal and topographically related lesions. For diffuse white matter pathology of similar appearance in vascular and neurodegenerative disease with dementia, there may be various at least partly contrasting aetiologies, which can be differentiated by the presence of even minor focal lesions in some cases. For the recognition of such subtle variations in the spectrum of WMD, modern imaging techniques are crucial for detailed clinical diagnosis and attempts at therapeutic intervention.
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White matter alterations in Alzheimer's disease cannot be fully accounted for as degenerative processes secondary to grey matter damage.
“Such white matter alterations cannot be fully accounted for as degenerative processes secondary to grey matter damage (Brun and Englund, 1986; Englund, 1998; Agosta et al., 2011), but may stem from vascular amyloid deposition and microvascular damage (Weller et al., 2009).”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Englund, 1998
Neurodegeneration is the major driver of cognitive decline in Alzheimer's disease.
“Neurodegeneration, which encompasses brain structural damage at the micro-and macroscopic scale, occurs in both white and grey matter, and is the major driver of cognitive decline in AD (Englund 1998, Jack Jr. et al 1997, Frisoni et al 2002, McDonald et al 2012).”
From White matter microstructural abnormality precedes cortical volumetric decline in Alzheimer’s disease: evidence from data-driven disease progression modelling (2022) · cites this paper as Englund 1998
Cites
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Pathologic correlates of incidental MRI white matter signal hyperintensities
Fazekas, F., Kleinert, R., Offenbacher, H., Schmidt, R., Kleinert, G., Payer, F., Radner, H., & Lechner, H. (1993) · Neurology · doi:10.1212/wnl.43.9.1683 · Cited by 1,619 · see citing works
A white matter disorder in dementia of the Alzheimer type: A pathoanatomical study
Brun, A., & Englund, E. (1986) · Annals of Neurology · doi:10.1002/ana.410190306 · Cited by 1,014 · see citing works
Self-citationULTRASTRUCTURAL STUDIES IN ALZHEIMER'S PRESENILE DEMENTIA.
Terry, R. D., Gonatas, N. K., & WEISS, M. (1964) · PubMed · Cited by 650 · see citing works
Regional pattern of degeneration in Alzheimer's disease: neuronal loss and histopathological grading
Brun, A., & Englund, E. M. (1981) · Histopathology · doi:10.1111/j.1365-2559.1981.tb01818.x · Cited by 559 · see citing works
Self-citationHistopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging
Scheltens, P., Barkhof, F., Leys, D., Wolters, E. C., Ravid, R., & Kamphorst, W. (1995) · Neurology · doi:10.1212/wnl.45.5.883 · Cited by 344 · see citing works
Buée, L., Hof, P. R., Bouras, C., Delacourte, A., Perl, D. P., Morrison, J. H., & Fillit, H. M. (1994) · Acta Neuropathologica · doi:10.1007/bf00294173 · Cited by 331 · see citing works
Why are stroke patients prone to develop dementia?
Pasquier, F., & Leys, D. (1997) · Journal of Neurology · doi:10.1007/s004150050064 · Cited by 253 · see citing works
WHITE MATTER CHANGES IN DEMENTIA OF ALZHEIMER'S TYPE: BIOCHEMICAL AND NEUROPATHOLOGICAL CORRELATES
ENGLUND, E., BRUN, A., & ALLING, C. (1988) · Brain · doi:10.1093/brain/111.6.1425 · Cited by 228 · see citing works
Self-citationWhite-Matter Hyperintensity and Neuropsychological Functions in Dementia and Healthy Aging
Almkvist, O., Wahlund, L., Andersson-Lundman, G., Basun, H., & Bäckman, L. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530300062011 · Cited by 195 · see citing works
Degeneration of vascular muscle cells in cerebral amyloid angiopathy of Alzheimer disease
Kawai, M., Kalaria, R. N., Cras, P. P., Siedlak, S. L., Velasco, M. E., Shelton, E. R., Chan, H. W., Greenberg, B., & Perry, G. L. (1993) · Brain Research · doi:10.1016/0006-8993(93)90021-e · Cited by 189 · see citing works
Patchy, periventricular white matter lesions in the elderly : common observation during NMR imaging
Bradley, W. J. (1984) · Medical Entomology and Zoology · Cited by 186 · see citing works
Clinicopathologic correlations of cranial magnetic resonance imaging of periventricular white matter
Leifer, D., Buonanno, F. S., & Richardson, E. P. (1990) · Neurology · doi:10.1212/wnl.40.6.911 · Cited by 169 · see citing works
Englund, E. M., & Brun, A. (1990) · Histopathology · doi:10.1111/j.1365-2559.1990.tb01542.x · Cited by 138 · see citing works
Self-citationNeuropathologic Correlates of Leuko-araiosis
Janota, I., Mirsen, T. R., Hachinski, V., et al. (1989) · Archives of Neurology · doi:10.1001/archneur.1989.00520460118023 · Cited by 138 · see citing works
Vinters, H., Secor, D. L., Read, S., Frazee, J., Tomiyasu, U., Stanley, T., Ferreiro, J., & Akers, M.-A. (1994) · Ultrastructural Pathology · doi:10.3109/01913129409023202 · Cited by 126 · see citing works
Relationship between vascular factors and white matter low attenuation of the brain
Räihä, I. J., Tarvonen-Schröder, S., Kurki, T. J. I., Rajala, T., & Sourander, L. (1993) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1993.tb05509.x · Cited by 118 · see citing works
Tomimoto, H., Akiguchi, I., Wakita, H., Suenaga, T., Nakamura, S., & Kimura, J. (1997) · Acta Neuropathologica · doi:10.1007/s004010050686 · Cited by 114 · see citing works
Subcortical arteriosclerotic encephalopathy: CT spectrum and pathologic correlation
Lotz, P. R., Ballinger, W. E., & Quisling, R. G. (1986) · American Journal of Roentgenology · doi:10.2214/ajr.147.6.1209 · Cited by 104 · see citing works
Clinical features of leuko-araiosis.
Tarvonen-Schröder, S., Röyttä, M., Räihä, I. J., Kurki, T. J. I., Rajala, T., & Sourander, L. (1996) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.60.4.431 · Cited by 84 · see citing works
CORRELATIONS BETWEEN HISTOPATHOLOGIC WHITE MATTER CHANGES AND PROTON MR RELAXATION TIMES IN DEMENTIA
Enolund, E., Brun, A., & Persson, B. (1987) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-198701030-00008 · Cited by 78 · see citing works
Waldemar, G., Christiansen, P., Larsson, H. B. W., Høgh, P., Laursen, H. B., Lassen, N. A., & Paulson, O. B. (1994) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.57.12.1458 · Cited by 74 · see citing works
Kawamura, J., Meyer, J. S., Ichijo, M., et al. (1993) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.56.2.182 · Cited by 44 · see citing works
Amar, K. A., Bucks, R. S., Lewis, T., et al. (1996) · Age and Ageing · doi:10.1093/ageing/25.6.443 · Cited by 36 · see citing works
Rarefied White Matter in Patients with Alzheimer Disease
Brilliant, M., Hughes, L. F., Anderson, D., Ghobrial, M. W., & Elble, R. J. (1995) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199505000-00008 · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
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White matter hyperintensities, cognitive impairment and dementia: an update
Prins, N. D., & Scheltens, P. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.10 · Cited by 1,284 · see citing works
Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations
Gouw, A. A., Seewann, A., van der Flier, W. M., Barkhof, F., Rozemuller, A. M., Scheltens, P., & Geurts, J. J. G. (2011) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.204685 · Cited by 766 · see citing works
Han, X., M. Holtzman, D., W. McKeel, D., Kelley, J., & Morris, J. C. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00997.x · Cited by 626 · see citing works
White matter changes in mild cognitive impairment and AD: a diffusion tensor imaging study
Medina, D., deToledo-Morrell, L., Urresta, F., Gabrieli, J. D. E., Moseley, M., Fleischman, D., Bennett, D. A., Leurgans, S., Turner, D. A., & Stebbins, G. T. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.026 · Cited by 492 · see citing works
Kalaria, R. N. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1571-z · Cited by 441 · see citing works
A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease
Sexton, C. E., Kalu, U. G., Filippini, N., Mackay, C. E., & Ebmeier, K. P. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.019 · Cited by 410 · see citing works
Vascular pathology in the aged human brain
Grinberg, L. T., & Thal, D. R. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0652-7 · Cited by 345 · see citing works
Magnetic Resonance Imaging of Myelin
Laule, C., Vavasour, I. M., Kolind, S. H., Li, D. K. B., Traboulsee, T. L., Moore, G. R. W., & MacKay, A. L. (2007) · Neurotherapeutics · doi:10.1016/j.nurt.2007.05.004 · Cited by 334 · see citing works
Mild cognitive impairment and Alzheimer disease: regional diffusivity of water
Kantarci, K., Jack, C. R., Xu, Y. C., Campeau, N. G., O’Brien, P. C., Smith, G. E., Ivnik, R. J., Boeve, B. F., Kokmen, E., Tangalos, E. G., et al. (2001) · Radiology · doi:10.1148/radiology.219.1.r01ap14101 · Cited by 300 · see citing works
Towards defining the neuropathological substrates of vascular dementia
Kalaria, R. N., Kenny, R. A., Ballard, C. G., Perry, R., Ince, P., & Polvikoski, T. (2004) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.09.019 · Cited by 291 · see citing works
White matter damage in Alzheimer disease and its relationship to gray matter atrophy
Agosta, F., Pievani, M., Sala, S., Geroldi, C., Galluzzi, S., Frisoni, G. B., & Filippi, M. (2011) · Radiology · doi:10.1148/radiol.10101284 · Cited by 288 · see citing works
Bosch, B., Arenaza-Urquijo, E. M., Rami, L., Sala-Llonch, R., Junqué, C., Solé-Padullés, C., Peña-Gómez, C., Bargalló, N., Molinuevo, J. L., & Bartrés-Faz, D. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.02.004 · Cited by 272 · see citing works
Simpson, J. E., Fernando, M. S., Clark, L., Ince, P. G., Matthews, F., Forster, G., O'Brien, J. T., Barber, R., Kalaria, R. N., Brayne, C., et al. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00828.x · Cited by 215 · see citing works
Cerebral Perfusion and Cerebrovascular Reactivity Are Reduced in White Matter Hyperintensities
Marstrand, J. R., Garde, E., Rostrup, E., Ring, P., Rosenbaum, S., Mortensen, E. L., & Larsson, H. B. W. (2002) · Stroke · doi:10.1161/01.str.0000012808.81667.4b · Cited by 215 · see citing works
Bocti, C., Swartz, R. H., Gao, F.-Q., Sahlas, D. J., Behl, P., & Black, S. E. (2005) · Stroke · doi:10.1161/01.str.0000183615.07936.b6 · Cited by 182 · see citing works
White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease
Araque Caballero, M. Á., Suárez-Calvet, M., Duering, M., Franzmeier, N., Benzinger, T., Fagan, A. M., Bateman, R. J., Jack, C. R., Levin, J., Dichgans, M., et al. (2018) · Brain · doi:10.1093/brain/awy229 · Cited by 179 · see citing works
“Such white matter alterations cannot be fully ac- counted for as degenerative processes secondary to grey matter damage (Brun and Englund, 1986; Englund, 1998; Agosta et al., 2011), but may stem from vascular amyloid deposition and microvascular damage (Weller et al., 2009).”
BackgroundBrain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome
Lange, G., DeLuca, J., Maldjian, J. A., Lee, H.-J., Tiersky, L. A., & Natelson, B. H. (1999) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(99)00243-9 · Cited by 154 · see citing works
Is Alzheimer’s a disease of the white matter?
Sachdev, P. S., Zhuang, L., Braidy, N., & Wen, W. (2013) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32835ed6e8 · Cited by 137 · see citing works
Nowrangi, M. A., Lyketsos, C. G., Leoutsakos, J. S., Oishi, K., Albert, M., Mori, S., & Mielke, M. M. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.05.2186 · Cited by 120 · see citing works
O'Dwyer, L., Lamberton, F., Bokde, A. L. W., Ewers, M., Faluyi, Y. O., Tanner, C., Mazoyer, B., O'Neill, D., Bartley, M., Collins, D. R., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021745 · Cited by 119 · see citing works
Associations of White Matter Hyperintensities with Cognitive Decline: A Longitudinal Study
Wang, Y.-L., Chen, W., Cai, W.-J., Hu, H., Xu, W., Wang, Z.-T., Cao, X.-P., Tan, L., Yu, J.-T., & Initiative, A. D. N. (2020) · Journal of Alzheimer’s Disease · doi:10.3233/jad-191005 · Cited by 92 · see citing works
Early and late onset Alzheimer’s disease patients have distinct patterns of white matter damage.
Canu, E., Frisoni, G. B., Agosta, F., Pievani, M., Bonetti, M., & Filippi, M. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.09.021 · Cited by 67 · see citing works
Libon, D. J., Price, C. C., Giovannetti, T., Swenson, R., Bettcher, B. M., Heilman, K. M., & Pennisi, A. (2008) · Stroke · doi:10.1161/strokeaha.107.489997 · Cited by 62 · see citing works
O'Dwyer, L., Lamberton, F., Matura, S., Scheibe, M., Miller, J., Rujescu, D., Prvulovic, D., & Hampel, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036024 · Cited by 34 · see citing works
Parker, C., Weston, P., Zhang, H., Oxtoby, N., & Initiative, T. A. D. N. (2022) · doi:10.1101/2022.07.12.499784 · Cited by 2 · see citing works
- Authors
- Englund, E.
- Affiliations
- Lund University (SE)
- Corresponding author
- Englund, Elisabet
- ORCID
- Englund, Elisabet
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 1998
- Volume
- 9
- Issue
- Suppl. 1
- Pages
- 6-12
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W2081825327
- Cited by
- 213
- References
- 25
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 6 · 2022: 4 · 2021: 9 · 2020: 4 · 2019: 6 · 2018: 8 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 4 · 2013: 9 · 2012: 11
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Dementia and Geriatric Cognitive Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lunds Universitet
- Stiftelsen Konsul Thure Carlssons Minne
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- white matter disease, Alzheimer's disease, vascular dementia, white matter degeneration, gliosis, Wallerian degeneration, vessel density, neuropathology
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Blood Vessels, Brain, Female, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Degeneration, Dementia, Vascular
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