Cholesterol, Atherosclerosis, and APOE in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Potential Mechanisms and Therapy
Duong MT, Nasrallah IM, Wolk DA, Chang CCY, Chang TY.. Frontiers in aging neuroscience, 2021-03-25
Topic: Amyloid, tau and blood-test diagnosis
Vascular contributions to cognitive impairment and dementia (VCID) are a common cause of cognitive decline, yet limited therapies exist. This cerebrovascular disease results in neurodegeneration via acute, chronic, local, and systemic mechanisms. The etiology of VCID is complex, with a significant impact from atherosclerosis. Risk factors including hypercholesterolemia and hypertension promote intracranial atherosclerotic disease and carotid artery stenosis (CAS), which disrupt cerebral blood flow and trigger ischemic strokes and VCID. Apolipoprotein E (APOE) is a cholesterol and phospholipid carrier present in plasma and various tissues. APOE is implicated in dyslipidemia and Alzheimer disease (AD); however, its connection with VCID is less understood. Few experimental models for VCID exist, so much of the present information has been drawn from clinical studies. Here, we review the literature with a focus on the clinical aspects of atherosclerotic cerebrovascular disease and build a working model for the pathogenesis of VCID. We describe potential intermediate steps in this model, linking cholesterol, atherosclerosis, and APOE with VCID. APOE4 is a minor isoform of APOE that promotes lipid dyshomeostasis in astrocytes and microglia, leading to chronic neuroinflammation. APOE4 disturbs lipid homeostasis in macrophages and smooth muscle cells, thus exacerbating systemic inflammation and promoting atherosclerotic plaque formation. Additionally, APOE4 may contribute to stromal activation of endothelial cells and pericytes that disturb the blood-brain barrier (BBB). These and other risk factors together lead to chronic inflammation, atherosclerosis, VCID, and neurodegeneration. Finally, we discuss potential cholesterol metabolism based approaches for future VCID treatment.
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APA 7th
Duong, M. T., Nasrallah, I. M., Wolk, D. A., Chang, C. C. Y., & Chang, T. Y. (2021). Cholesterol, Atherosclerosis, and APOE in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Potential Mechanisms and Therapy. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2021.647990
Vancouver
Duong MT, Nasrallah IM, Wolk DA, Chang CCY, Chang TY. Cholesterol, Atherosclerosis, and APOE in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Potential Mechanisms and Therapy. Frontiers in aging neuroscience. 2021. doi:10.3389/fnagi.2021.647990. PMID: 33841127.
BibTeX
@article{duong2021-33841127,
author = {Duong, M. T. and Nasrallah, I. M. and Wolk, D. A. and Chang, C. C. Y. and Chang, T. Y.},
title = {{Cholesterol, Atherosclerosis, and APOE in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Potential Mechanisms and Therapy}},
journal = {Frontiers in aging neuroscience},
year = {2021},
doi = {10.3389/fnagi.2021.647990},
pmid = {33841127},
url = {https://doi.org/10.3389/fnagi.2021.647990}
}
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Key findings
- This cerebrovascular disease results in neurodegeneration via acute, chronic, local, and systemic mechanisms.
- The etiology of VCID is complex, with a significant impact from atherosclerosis.
Why it matters
This review links cholesterol, atherosclerosis and APOE4 to vascular contributions to cognitive impairment and dementia, noting that few experimental models exist. It is a review of existing literature and does not report a new treatment or prevention result.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in aging neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Aging Neuroscience: journal h-index 174 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 106 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 4.4× 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 75 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ta‐Yuan Chang: h-index 60 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33841127) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 100 | — |
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Read the original
- DOI: 10.3389/fnagi.2021.647990
- PubMed: 33841127
- Original source →
- Free full text: Frontiers in Aging Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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