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Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study
Hofman A, Ott A, Breteler MM, Bots ML, Slooter AJ, van Harskamp F, van Duijn CN, Van Broeckhoven C et al.. Lancet (London, England), 1997-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimer's disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimer's disease. We investigated the frequency of dementia and its subtypes in relation to atherosclerosis and apolipoprotein E. Methods We did a population-based study of 284 patients with dementia, 207 of whom had Alzheimer's disease, and 1698 individuals who were not demented. Indicators of atherosclerosis included vessel wall thickness and plaques of the carotid arteries, assessed by ultrasonography, and the ratio of ankle-to-brachial systolic blood pressure as a measure of generalised atherosclerosis. Based on these indicators participants were scored from 0 (no atherosclerosis) to 3 (severe atherosclerosis) for degree of atherosclerosis. Apolipoprotein-E polymorphisms were assessed in 246 patients and in 928 controls. Findings All indicators of atherosclerosis were associated with dementia (odds ratios ranging from 1.3 to 1.9) and its major subtypes Alzheimer's disease (odds ratios 1.3-1.8) and vascular dementia (odds ratios 1.9-3.2). The frequencies of all dementia. Alzheimer's disease, and vascular dementia increased with the degree of atherosclerosis. The odds ratio for Alzheimer's disease in those with severe atherosclerosis compared with those without atherosclerosis was 3.0 (95% CI 1.5-6.0; p = 0.001). In participants with the apolipoprotein-E epsilon 4 genotype and an atherosclerosis score of 2 or 3 the odds ratio for all dementia was 4.5 (2.0-10.1; p Interpretation These findings suggest that dementia and its two major subtypes Alzheimer's disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein E and atherosclerosis in the aetiology of Alzheimer's disease.
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APA 7th
Hofman, A., Ott, A., Breteler, M. M., Bots, M. L., Slooter, A. J., van Harskamp, F., et al. (1997). Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet (London, England). https://doi.org/10.1016/s0140-6736(96)09328-2
Vancouver
Hofman A, Ott A, Breteler MM, Bots ML, Slooter AJ, van Harskamp F, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet (London, England). 1997. doi:10.1016/s0140-6736(96)09328-2. PMID: 9111537.
BibTeX
@article{hofman1997-9111537,
author = {Hofman, A. and Ott, A. and Breteler, M. M. and Bots, M. L. and Slooter, A. J. and van Harskamp, F. and van Duijn, C. N. and Van Broeckhoven, C. and others},
title = {{Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study}},
journal = {Lancet (London, England)},
year = {1997},
doi = {10.1016/s0140-6736(96)09328-2},
pmid = {9111537},
url = {https://doi.org/10.1016/s0140-6736(96)09328-2}
}
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Key findings
- The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimer's disease.
- Findings All indicators of atherosclerosis were associated with dementia (odds ratios ranging from 1.3 to 1.9) and its major subtypes Alzheimer's disease (odds ratios 1.3-1.8) and vascular dementia (odds ratios 1.9-3.2).
- The odds ratio for Alzheimer's disease in those with severe atherosclerosis compared with those without atherosclerosis was 3.0 (95% CI 1.5-6.0; p = 0.001).
- In participants with the apolipoprotein-E epsilon 4 genotype and an atherosclerosis score of 2 or 3 the odds ratio for all dementia was 4.5 (2.0-10.1; p < 0.001), for Alzheimer's disease was 3.9 (1.6-9.6; p = 0.002), and for vascular dementia was 19.8 (4.1-95.0; p < 0.001).
Why it matters
In this Rotterdam population study of 284 people with dementia (207 with Alzheimer's disease) and 1,698 without, signs of hardened arteries, measured by neck-artery ultrasound and an ankle-arm blood-pressure ratio, were more common in those with dementia. People with severe atherosclerosis had about three times the odds of having Alzheimer's disease as people with none (odds ratio 3.0, 95% CI 1.5–6.0). Dementia was more common still in people who carried the APOE ε4 gene variant and had moderate-to-severe atherosclerosis (odds ratio 4.5 for all dementia). The study looked at people at one point in time, so it shows a link, not that atherosclerosis causes Alzheimer's or that treating it would prevent the disease.
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Study details
- Participants284
- Evidence strengthLow
How this study scored 62/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Lancet (London, England)) |
| Journal's citation record | 4 / 4 | The Lancet: journal h-index 1,205 (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 | 1 / 5 | 1997 — older than 20 years, still counted |
| Sample size | 2 / 4 | 284 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 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 1,381 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 44.5 citations a year over 31 year(s) since 1997 |
| Impact for its field and year | 6 / 6 | Cited 47.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 100 other studies in this library |
| Still being cited | 3 / 4 | Cited 51 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Diederick E. Grobbee: h-index 28 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Erasmus MC: institution h-index 1,321 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9111537) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
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