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Vascular burden and Alzheimer disease pathologic progression
Lo RY, Jagust WJ, Alzheimer's Disease Neuroimaging Initiative.. Neurology, 2012-09-12
Topic: Amyloid, tau and blood-test diagnosis
Objective To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. Methods The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. Results Cardiovascular risk profiles were not predictive of progression in CSF β₄₂-amyloid, [¹⁸F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. Conclusion Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.
Key findings
- Results Cardiovascular risk profiles were not predictive of progression in CSF β₄₂-amyloid, [¹⁸F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy.
- Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function.
- Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC.
- Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups.
- These findings remained unchanged after accounting for APOE4.
Why it matters
Cardiovascular risk profiles did not predict progression in CSF β-amyloid, FDG PET uptake, or MRI hippocampal atrophy. Greater white matter hyperintensities were linked to worse executive function and, in normal cognition, faster executive decline and lower FDG uptake, but were otherwise not associated with CSF or MRI biomarkers.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 60/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| 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 | 7 / 12 | A longitudinal study following the same 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 | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 156 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.8 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 12.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 18 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Daniel Varón: h-index 49 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 37 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22972646) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Lo, R. Y., Jagust, W. J., & Alzheimer's Disease Neuroimaging Initiative. (2012). Vascular burden and Alzheimer disease pathologic progression. Neurology. https://doi.org/10.1212/wnl.0b013e31826c1b9d
Vancouver
Lo RY, Jagust WJ, Alzheimer's Disease Neuroimaging Initiative. Vascular burden and Alzheimer disease pathologic progression. Neurology. 2012. doi:10.1212/wnl.0b013e31826c1b9d. PMID: 22972646.
BibTeX
@article{lo2012-22972646,
author = {Lo, R. Y. and Jagust, W. J. and {Alzheimer's Disease Neuroimaging Initiative}},
title = {{Vascular burden and Alzheimer disease pathologic progression}},
journal = {Neurology},
year = {2012},
doi = {10.1212/wnl.0b013e31826c1b9d},
pmid = {22972646},
url = {https://doi.org/10.1212/wnl.0b013e31826c1b9d}
}
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