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Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults
Rizvi B, Lao PJ, Chesebro AG, Dworkin JD, Amarante E, Beato JM, Gutierrez J, Zahodne LB et al.. JAMA network open, 2021-10-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH), is associated with cognitive decline and risk of clinical Alzheimer disease (AD). One way in which small vessel cerebrovascular disease could contribute to AD is through the promotion of neurodegeneration; the effect of small vessel cerebrovascular disease on neurodegeneration may differ across racial and ethnic groups. Objective To examine whether WMH volume is associated with cortical thinning over time and subsequent memory functioning and whether the association between WMH volume and cortical thinning differs among racial and ethnic groups. Design, setting, and participants This longitudinal community-based cohort study included older adults from northern Manhattan who were participants in the Washington Heights-Inwood Columbia Aging Project. Participants underwent two 3T magnetic resonance imaging (MRI) scans a mean of 4 years apart. Data were collected from March 2011 to January 2020. Exposures Total and regional WMH volumes. Main outcomes and measures The association of total and regional WMH volumes with cortical thinning over time was tested using general linear models in a vertexwise analysis. Cortical thinning was measured vertexwise by symmetrized percent change between 2 time points. The association of changes in cortical thickness with memory and whether this association differed by race and ethnicity was also analyzed. Delayed memory was a secondary outcome. Results In 303 participants (mean [SD] age, 73.16 [5.19] years, 181 [60%] women, 96 [32%] non-Hispanic White, 113 [37%] Non-Hispanic Black, 94 [31%] Hispanic), baseline WMH volumes were associated with cortical thinning in medial temporal and frontal/parietal regions. Specifically, total WMH volume was associated with cortical thinning in the right caudal middle frontal cortex (P = .001) and paracentral cortex (P = .04), whereas parietal WMH volume was associated with atrophy in the left entorhinal cortex (P = .03) and right rostral middle frontal (P Conclusions and relevance In this study, small vessel cerebrovascular disease, operationalized as WMH, was associated with subsequent cortical atrophy in regions that overlap with typical AD neurodegeneration patterns, particularly among non-Hispanic Black older adults. Cerebrovascular disease may affect risk and progression of AD by promoting neurodegeneration and subsequent memory decline.
Key findings
- Importance Small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH), is associated with cognitive decline and risk of clinical Alzheimer disease (AD).
- Objective To examine whether WMH volume is associated with cortical thinning over time and subsequent memory functioning and whether the association between WMH volume and cortical thinning differs among racial and ethnic groups.
- Results In 303 participants (mean [SD] age, 73.16 [5.19] years, 181 [60%] women, 96 [32%] non-Hispanic White, 113 [37%] Non-Hispanic Black, 94 [31%] Hispanic), baseline WMH volumes were associated with cortical thinning in medial temporal and frontal/parietal regions.
- Specifically, total WMH volume was associated with cortical thinning in the right caudal middle frontal cortex (P = .001) and paracentral cortex (P = .04), whereas parietal WMH volume was associated with atrophy in the left entorhinal cortex (P = .03) and right rostral middle frontal (P < .001), paracentral (P < .001), and pars triangularis (P = .02) cortices.
Why it matters
In 303 older adults from northern Manhattan who had two MRI scans about 4 years apart, people with more white matter hyperintensities (an MRI sign of small blood vessel disease) at the start went on to show more thinning of the cortex in areas typical of Alzheimer's disease, including the entorhinal cortex in the medial temporal lobe. The authors report this link was seen "particularly among non-Hispanic Black older adults" and suggest blood vessel disease "may" add to Alzheimer's progression by promoting brain cell loss. This is an observational association, not proof of cause, and the study did not test any treatment or prevention.
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Study details
- Study designcohort study
- Participants303
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA network open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 303 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 79 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 7.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 3 / 4 | Cited 53 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Adam M. Brickman: h-index 87 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Michigan: institution h-index 2,240 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34609497) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
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Read the original
- DOI: 10.1001/jamanetworkopen.2021.25166
- PubMed: 34609497
- Original source →
- Free full text: JAMA Network Open →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Rizvi, B., Lao, P. J., Chesebro, A. G., Dworkin, J. D., Amarante, E., Beato, J. M., et al. (2021). Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults. JAMA network open. https://doi.org/10.1001/jamanetworkopen.2021.25166
Vancouver
Rizvi B, Lao PJ, Chesebro AG, Dworkin JD, Amarante E, Beato JM, et al. Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults. JAMA network open. 2021. doi:10.1001/jamanetworkopen.2021.25166. PMID: 34609497.
BibTeX
@article{rizvi2021-34609497,
author = {Rizvi, B. and Lao, P. J. and Chesebro, A. G. and Dworkin, J. D. and Amarante, E. and Beato, J. M. and Gutierrez, J. and Zahodne, L. B. and others},
title = {{Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults}},
journal = {JAMA network open},
year = {2021},
doi = {10.1001/jamanetworkopen.2021.25166},
pmid = {34609497},
url = {https://doi.org/10.1001/jamanetworkopen.2021.25166}
}
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