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Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study
Ott A, Slooter AJ, Hofman A, van Harskamp F, Witteman JC, Van Broeckhoven C, van Duijn CM, Breteler MM.. Lancet (London, England), 1998-06-01
Topic: Risk, prevention and care in population studies
Background Previous studies suggested a protective effect of smoking on Alzheimer's disease, but most were case-control studies based on prevalent cases. The findings of prospective studies on the association between smoking and the risk of dementia are inconclusive. Methods We did a population-based follow-up study of elderly people who were initially free of dementia. 6870 people aged 55 years and older agreed to take part. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers. During follow-up, we recorded all incident cases of dementia. We used never smokers as the reference category to calculate relative risks of dementia and Alzheimer's disease by Cox proportional hazards regression, after adjustment for age, sex, education, and alcohol intake. We also examined modification of risk by age, sex, and the apolipoprotein E (APOE) genotype. Findings During mean follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were detected, of which 105 were Alzheimer's disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for Alzheimer's disease in individuals without the APOEepsilon4 allele (4.6 [1.5-14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]). Interpretation Smoking was associated with a doubling of the risk of dementia and Alzheimer's disease. Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimer's disease.
Key findings
- Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimer's disease (2.3 [1.3-4.1]).
- Interpretation Smoking was associated with a doubling of the risk of dementia and Alzheimer's disease.
- Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimer's disease.
Why it matters
In this cohort, smokers had about double the risk of dementia and Alzheimer's disease compared with never smokers. This identifies smoking as a risk factor but does not test a treatment or cure.
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Study details
- Study designcase-control study
- Participants6,870
- Evidence strengthModerate
How this study scored 67/100
Published in a top-tier journal, and it is a case-control study. Scored zero for effect reported and randomised / 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 | 6 / 12 | A case-control study |
| 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 | 3 / 4 | 6,870 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 | 6 / 7 | Cited 536 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.9 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 4 / 6 | Cited 17.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 34 other studies in this library |
| Still being cited | 2 / 4 | Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Monique M.B. Breteler: h-index 162 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Erasmus MC: institution h-index 1,321 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9652667) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 67 / 100 | — |
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Read the original
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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 8 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
Ott, A., Slooter, A. J., Hofman, A., van Harskamp, F., Witteman, J. C., Van Broeckhoven, C., et al. (1998). Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study. Lancet (London, England). https://doi.org/10.1016/s0140-6736(97)07541-7
Vancouver
Ott A, Slooter AJ, Hofman A, van Harskamp F, Witteman JC, Van Broeckhoven C, et al. Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study. Lancet (London, England). 1998. doi:10.1016/s0140-6736(97)07541-7. PMID: 9652667.
BibTeX
@article{ott1998-9652667,
author = {Ott, A. and Slooter, A. J. and Hofman, A. and van Harskamp, F. and Witteman, J. C. and Van Broeckhoven, C. and van Duijn, C. M. and Breteler, M. M.},
title = {{Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study}},
journal = {Lancet (London, England)},
year = {1998},
doi = {10.1016/s0140-6736(97)07541-7},
pmid = {9652667},
url = {https://doi.org/10.1016/s0140-6736(97)07541-7}
}
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