White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer’s disease. Evidence for heterogeneity
Abstract
In a prospective magnetic resonance imaging (MRI) study we evaluated the prevalence and severity of white matter changes in 29 patients with Alzheimer's Disease (AD) and 24 age-matched healthy elderly, all without cerebrovascular risk factors. The AD patients were divided into two groups according to age at onset of symptoms, one with presenile onset AD (n = 13) and one with senile onset AD (n = 16), who were matched for dementia severity. Signal hyperintensities were rated using a semiquantitative scoring method, separately in the periventricular region (PVH) and in the lobar white matter (WMH), as well as in the basal ganglia (BGH) and in the infratentorial region (ITFH). Cortical atrophy as a parameter of grey matter involvement was rated on a 0 (absent) to 3 (severe) scale. We found PVH, WMH and BGH scores to be significantly higher in senile onset AD patients than in age-matched controls. By means of multiple linear logistic regression we found that PVH, WMH and BGH scores were significantly dependent on the diagnosis of senile onset AD, while the PVH score also showed a significant age dependency. Cortical atrophy did not differ significantly between presenile onset AD and senile onset AD patients. These results indicate that presenile onset AD and senile onset AD patients differ with respect to white matter involvement, but not with respect to grey matter involvement on MRI. Since cerebrovascular risk factors were excluded these findings may indicate that senile onset AD patients display more small vessel involvement (arteriolosclerosis) than presenile onset AD patients, suggesting additional (microvascular) factors for the dementia syndrome in senile onset AD. Our data lend support to the growing body of evidence that AD is heterogeneous, consisting of at least two types. Based on our findings two forms can be distinguished: (i) a 'pure' form of the disease, usually with early disease onset, and no more white matter changes than normal for age; (ii) a 'mixed' form, usually with disease onset later in life, and showing more white matter changes on MRI than normal for age.
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Age-associated myelin breakdown is seen in MRI scans of patients from age 50 on, which is accentuated in APOE4 patients.
“Age-associated myelin breakdown is seen in MRI scans of patients from age 50 on, which is accentuated in APOE4 patients (Scheltens et al. , 1992; Bartzokis, 2011).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Scheltens et al., 1992
AD subjects show more pervasive white matter change.
“AD subjects show more pervasive white matter change [42–46].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [46]
MRI data indicate that individuals with the APOEε4 risk allele have accentuated myelin breakdown in AD.
“magnetic resonance imaging (MRI) data indicate that individuals with the risk allele APOEε4 have accentuated myelin breakdown in AD [128, 129].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [129]
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- Authors
- SCHELTENS, P., BARKHOF, F., VALK, J., ALGRA, P. R., HOOP, R. G. V. D., NAUTA, J., & WOLTERS, E. C.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 1992
- Volume
- 115
- Issue
- 3
- Pages
- 735-748
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2071837886
- Cited by
- 314
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 7 · 2018: 1 · 2017: 5 · 2016: 7 · 2015: 11 · 2014: 9 · 2013: 7 · 2012: 9
- FWCI
- 8.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- Alzheimer's disease, white matter lesions, disease heterogeneity, periventricular white matter hyperintensities, white matter hyperintensities, basal ganglia hyperintensity, cortical atrophy, arteriolosclerosis, cerebral small vessel disease, age of onset, dementia
- MeSH terms
- Aged, Alzheimer Disease, Basal Ganglia, Brain, Cerebral Ventricles, Female, Humans, Magnetic Resonance Imaging, Male, Meninges, Middle Aged, Prospective Studies
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