Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study
Slooter AJ, Cruts M, Kalmijn S, Hofman A, Breteler MM, Van Broeckhoven C, van Duijn CM.. Archives of neurology, 1998-07-01
Topic: Amyloid, tau and blood-test diagnosis
Objectives To provide risk estimates of dementia and Alzheimer disease as a function of the apolipoprotein E (APOE) genotypes and to assess the proportion of dementia that is attributable to the APOE genotypes. Design Case-control study nested in a population-based cohort study with a mean (SD) follow-up of 2.1 (0.9) years. Setting General population in Rotterdam, the Netherlands. Participants A total of 134 patients with incident dementia and a random sample of 997 nondemented control subjects. No participant had dementia at baseline. Main outcome measures Odds ratios for dementia and Alzheimer disease, the fraction of dementia attributable to the APOE epsilon4 allele, and the proportion of the variance in age at the onset of dementia explained by the APOE genotypes. Results Persons with the epsilon4/4 genotype had a more than 10-fold higher risk of dementia (odds ratio, 11.2; 95% confidence interval, 3.6-35.2), and subjects with the epsilon3/4 genotype had a 1.7-fold increased risk of dementia (95% confidence interval, 1.0-2.9) as compared with persons with the epsilon3/3 genotype. The proportion of patients with dementia that is attributable to the epsilon4 allele was estimated to be 20%. The APOE genotypes explained up to 10% of the variance in age at the onset of dementia. The association between the epsilon4 allele and dementia was strongest in the youngest age category and in those with a family history of dementia. Conclusions The APOE genotype is an important determinant of the risk of dementia. At a population level, however, other factors than the APOE genotype may play an important role in the cause of dementia.
Key findings
- Results Persons with the epsilon4/4 genotype had a more than 10-fold higher risk of dementia (odds ratio, 11.2; 95% confidence interval, 3.6-35.2), and subjects with the epsilon3/4 genotype had a 1.7-fold increased risk of dementia (95% confidence interval, 1.0-2.9) as compared with persons with the epsilon3/3 genotype.
Why it matters
In this population-based study, people with the APOE epsilon4/4 genotype had more than a 10-fold higher risk of dementia and those with epsilon3/4 had a 1.7-fold higher risk compared with epsilon3/3. About 20% of dementia cases were estimated to be attributable to the epsilon4 allele, and APOE genotypes explained up to 10% of the variance in age at dementia onset, which informs risk understanding rather than offering a treatment.
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Study details
- Study designcohort study
- Participants134
- Evidence strengthModerate
How this study scored 69/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| 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 | 1998 — older than 20 years, still counted |
| Sample size | 2 / 4 | 134 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 | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 6 / 7 | Cited 401 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.4 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 4 / 6 | Cited 8.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 33 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Cornelia M. van Duijn: h-index 237 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Erasmus MC: institution h-index 1,321 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9678314) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
Full text: free to read — Unpaywall lists this copy as free to read: the link above (checked 10 Oct 2026).
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Slooter, A. J., Cruts, M., Kalmijn, S., Hofman, A., Breteler, M. M., Van Broeckhoven, C., et al. (1998). Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study. Archives of neurology. https://doi.org/10.1001/archneur.55.7.964
Vancouver
Slooter AJ, Cruts M, Kalmijn S, Hofman A, Breteler MM, Van Broeckhoven C, et al. Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study. Archives of neurology. 1998. doi:10.1001/archneur.55.7.964. PMID: 9678314.
BibTeX
@article{slooter1998-9678314,
author = {Slooter, A. J. and Cruts, M. and Kalmijn, S. and Hofman, A. and Breteler, M. M. and Van Broeckhoven, C. and van Duijn, C. M.},
title = {{Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study}},
journal = {Archives of neurology},
year = {1998},
doi = {10.1001/archneur.55.7.964},
pmid = {9678314},
url = {https://doi.org/10.1001/archneur.55.7.964}
}
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