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Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort
Sipilä PN, Heikkilä N, Lindbohm JV, Hakulinen C, Vahtera J, Elovainio M, Suominen S, Väänänen A et al.. The Lancet. Infectious diseases, 2021-06-21
Topic: Risk, prevention and care in population studies
Existing studies have included a narrow range of infectious diseases, relied on short follow-up periods, and provided little evidence for whether the increased risk is limited to specific dementia subtypes or attributable to specific microbes rather than infection burden. Hospitalisation for any infectious disease was associated with increased dementia risk in the primary cohort (adjusted HR [aHR] 1·48 [95% CI 1·37-1·60]) and replication cohort (2·60 [2·38-2·83]). Although the greatest dementia risk was seen for central nervous system (CNS) infections versus no infection (aHR 3·01 [95% CI 2·07-4·37]), excess risk was also evident for extra-CNS infections (1·47 [1·36-1·59]). Although we found little difference in the infection-dementia association by type of infection, associations were stronger for vascular dementia than for Alzheimer's disease (aHR 2·09 [95% CI 1·59-2·75] versus aHR 1·20 [1·08-1·33] in the primary cohort and aHR 3·28 [2·65-4·04] versus aHR 1·80 [1·53-2·13] in the replication cohort). Interpretation Severe infections requiring hospital treatment are associated with long-term increased risk of dementia, including vascular dementia and Alzheimer's disease. This association is not limited to CNS infections, suggesting that systemic effects are sufficient to affect the brain.
Key findings
- Existing studies have included a narrow range of infectious diseases, relied on short follow-up periods, and provided little evidence for whether the increased risk is limited to specific dementia subtypes or attributable to specific microbes rather than infection burden.
- Hospitalisation for any infectious disease was associated with increased dementia risk in the primary cohort (adjusted HR [aHR] 1·48 [95% CI 1·37-1·60]) and replication cohort (2·60 [2·38-2·83]).
- Although the greatest dementia risk was seen for central nervous system (CNS) infections versus no infection (aHR 3·01 [95% CI 2·07-4·37]), excess risk was also evident for extra-CNS infections (1·47 [1·36-1·59]).
- Although we found little difference in the infection-dementia association by type of infection, associations were stronger for vascular dementia than for Alzheimer's disease (aHR 2·09 [95% CI 1·59-2·75] versus aHR 1·20 [1·08-1·33] in the primary cohort and aHR 3·28 [2·65-4·04] versus aHR 1·80 [1·53-2·13] in the replication cohort).
- Interpretation Severe infections requiring hospital treatment are associated with long-term increased risk of dementia, including vascular dementia and Alzheimer's disease.
Why it matters
This large observational study found that hospital treatment for severe infections was associated with a long-term increased risk of dementia, including vascular dementia and Alzheimer's disease, and that the association was not limited to infections of the central nervous system. It shows an association only and does not prove that preventing or treating infections would prevent Alzheimer's disease.
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Study details
- Study designcohort study
- Participants490
- Evidence strengthModerate
How this study scored 70/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Lancet. Infectious diseases) |
| Journal's citation record | 3 / 4 | The Lancet Infectious Diseases: journal h-index 373 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 490 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 | 5 / 7 | Cited 195 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.9 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 18.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 3 / 4 | Cited 134 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Mika Kivimäki: h-index 208 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34166620) |
| Free to read | 2 / 2 | Free to read |
| Total | 70 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/s1473-3099(21)00144-4
- PubMed: 34166620
- Original source →
- Free full text: The Lancet Infectious Diseases →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Sipilä, P. N., Heikkilä, N., Lindbohm, J. V., Hakulinen, C., Vahtera, J., Elovainio, M., et al. (2021). Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort. The Lancet. Infectious diseases. https://doi.org/10.1016/s1473-3099(21)00144-4
Vancouver
Sipilä PN, Heikkilä N, Lindbohm JV, Hakulinen C, Vahtera J, Elovainio M, et al. Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort. The Lancet. Infectious diseases. 2021. doi:10.1016/s1473-3099(21)00144-4. PMID: 34166620.
BibTeX
@article{sipila2021-34166620,
author = {Sipilä, P. N. and Heikkilä, N. and Lindbohm, J. V. and Hakulinen, C. and Vahtera, J. and Elovainio, M. and Suominen, S. and Väänänen, A. and others},
title = {{Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort}},
journal = {The Lancet. Infectious diseases},
year = {2021},
doi = {10.1016/s1473-3099(21)00144-4},
pmid = {34166620},
url = {https://doi.org/10.1016/s1473-3099(21)00144-4}
}
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