Home › Research › Brain scans and imaging
APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia
Mirza SS, Saeed U, Knight J, Ramirez J, Stuss DT, Keith J, Nestor SM, Yu D et al.. Neurology, 2019-10-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To determine if APOE ε4 influences the association between white matter hyperintensities (WMH) and cognitive impairment in Alzheimer disease (AD) and dementia with Lewy bodies (DLB). Methods A total of 289 patients (AD = 239; DLB = 50) underwent volumetric MRI, neuropsychological testing, and APOE ε4 genotyping. Total WMH volumes were quantified. Neuropsychological test scores were included in a confirmatory factor analysis to identify cognitive domains encompassing attention/executive functions, learning/memory, and language, and factor scores for each domain were calculated per participant. After testing interactions between WMH and APOE ε4 in the full sample, we tested associations of WMH with factor scores using linear regression models in APOE ε4 carriers (n = 167) and noncarriers (n = 122). We hypothesized that greater WMH volume would relate to worse cognition more strongly in APOE ε4 carriers. Findings were replicated in 198 patients with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI-I), and estimates from both samples were meta-analyzed. Results A significant interaction was observed between WMH and APOE ε4 for language, but not for memory or executive functions. Separate analyses in APOE ε4 carriers and noncarriers showed that greater WMH volume was associated with worse attention/executive functions, learning/memory, and language in APOE ε4 carriers only. In ADNI-I, greater WMH burden was associated with worse attention/executive functions and language in APOE ε4 carriers only. No significant associations were observed in noncarriers. Meta-analyses showed that greater WMH volume was associated with worse performance on all cognitive domains in APOE ε4 carriers only. Conclusion APOE ε4 may influence the association between WMH and cognitive performance in AD and DLB.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mirza, S. S., Saeed, U., Knight, J., Ramirez, J., Stuss, D. T., Keith, J., et al. (2019). APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia. Neurology. https://doi.org/10.1212/wnl.0000000000008377
Vancouver
Mirza SS, Saeed U, Knight J, Ramirez J, Stuss DT, Keith J, et al. APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia. Neurology. 2019. doi:10.1212/wnl.0000000000008377. PMID: 31575706.
BibTeX
@article{mirza2019-31575706,
author = {Mirza, S. S. and Saeed, U. and Knight, J. and Ramirez, J. and Stuss, D. T. and Keith, J. and Nestor, S. M. and Yu, D. and others},
title = {{APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia}},
journal = {Neurology},
year = {2019},
doi = {10.1212/wnl.0000000000008377},
pmid = {31575706},
url = {https://doi.org/10.1212/wnl.0000000000008377}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Results A significant interaction was observed between WMH and APOE ε4 for language, but not for memory or executive functions.
- Separate analyses in APOE ε4 carriers and noncarriers showed that greater WMH volume was associated with worse attention/executive functions, learning/memory, and language in APOE ε4 carriers only.
- In ADNI-I, greater WMH burden was associated with worse attention/executive functions and language in APOE ε4 carriers only.
- No significant associations were observed in noncarriers.
- Meta-analyses showed that greater WMH volume was associated with worse performance on all cognitive domains in APOE ε4 carriers only.
Why it matters
Greater white matter hyperintensity volume was associated with worse attention/executive functions, learning/memory and language only in APOE ε4 carriers, with no significant associations in noncarriers. This describes how a genetic factor and vascular brain changes relate to cognition, not a treatment, cure or prevention for Alzheimer's disease.
New to this subject? Start with our plain-English guide: Brain scans & tests →
Study details
- Study designmeta-analysis
- Participants167
- Evidence strengthHigh
How this study scored 70/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 67 of the 96 points we could judge it on, which is 70 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 167 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| Times cited | 4 / 7 | Cited 67 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.4 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 26 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31575706) |
| Free to read | 2 / 2 | Free to read |
| Points | 67 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 67 of the 96 points we could judge it on is 70 out of 100. |
| Total | 70 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 14.
Later studies that cite this one
4 studies in the alzhub library list this one in their references.
Related studies in Brain scans and imaging
Also tagged “precursor”
1,337 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,337 tagged studies.