Infectious Disease Burden and the Risk of Alzheimer’s Disease: A Population-Based Study
Open accessAbstract
Background: Previous studies suggested a link between various infectious pathogens and the development of Alzheimer’s disease (AD), posing the question whether infectious disease could present a novel modifiable risk factor. Objective: To assess whether infectious disease burden due to clinically apparent infections is associated with an increased risk of AD. Methods: We conducted a population-based nested case-control study using the United Kingdom Clinical Practice Research Datalink. We included all dementia-free subjects ≥50 years of age enrolling in the database between January 1988 and December 2017. Each case of AD identified during follow-up was matched with up to 40 controls. Conditional logistic regression estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with ≥1 infection diagnosed > 2 years before the index date compared with no infection during the study period. We further stratified by time since first infection and cumulative number of infections. Results: The cohort included overall 4,262,092 individuals (mean age at cohort entry 60.4 years; 52% female). During a median follow-up of 10.5 years, 40,455 cases of AD were matched to 1,610,502 controls. Compared with having no burden of infectious disease, having a burden of infectious disease was associated with an increase in the risk of AD (OR, 1.05; 95% CI, 1.02 to 1.08). The risk increased with longer time since first infection, peaking after 12–30 years (OR, 1.11; 95% CI, 1.05–1.17). The risk did not increase with cumulative number of infections. Conclusion: The overall risk of AD associated with infectious disease burden was small but increased gradually with longer time since first infection.
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Some evidence from electronic health records has not found a link between HSV-1/HSV-2 with AD.
“On the other hand, some evidence from electronic health records has not found a link between HSV-1/HSV-2 with AD [29].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [29]
The Exposure definition identifies clinically diagnosed herpes labialis or genitalis as the herpes simplex infections studied. Table 3 (displayed under Discussion; page unavailable) reports no statistically significant association between the combined herpes category and Alzheimer’s disease (adjusted OR 1.15, 95% CI 0.92–1.43). The paper does not report separate findings for HSV-1 and HSV-2, so the claim’s type-specific wording goes beyond its results. (LLM, conf=0.88)
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Cites
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Data Resource Profile: Clinical Practice Research Datalink (CPRD)
Herrett, E., Gallagher, A. M., Bhaskaran, K., Forbes, H., Mathur, R., van Staa, T., & Smeeth, L. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv098 · Cited by 2,667 · see citing works
Preclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria
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Singhrao, S. K., Harding, A., Poole, S., Kesavalu, L., & Crean, S. (2015) · Mediators of Inflammation · doi:10.1155/2015/137357 · Cited by 195 · see citing works
Lövheim, H., Olsson, J., Weidung, B., Johansson, A., Eriksson, S., Hallmans, G., & Elgh, F. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-161305 · Cited by 103 · see citing works
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Wu, X., Yang, H., He, S., Xia, T., Chen, D., Zhou, Y., Liu, J., Liu, M., & Sun, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.872542 · Cited by 73 · see citing works
Common vaccines and the risk of incident dementia: a population-based cohort study
Douros, A., Ante, Z., Suissa, S., & Brassard, P. (2023) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiac484 · Cited by 24 · see citing works
Self-citationWhat would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
Brutkiewicz, R. R., Cao, W., Morgan, D., Reis, R. S. D., Suryadevara, V., Willette, A. A., Willette, S. A., Wyatt-Johnson, S. K., & Duggan, M. R. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.05.009 · Cited by 3 · see citing works
- Authors
- Douros, A., Santella, C., Dell’Aniello, S., Azoulay, L., Renoux, C., Suissa, S., & Brassard, P.
- Affiliations
- Lady Davis Institute for Medical Research (CA)
- Corresponding author
- Brassard, Paul
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2021-05-04
- Volume
- 81
- Issue
- 1
- Pages
- 329-338
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W3138108848
- Cited by
- 37
- References
- 6
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 15 · 2023: 5 · 2022: 6 · 2021: 1
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- McGill University
- Alzheimer Society
- Fonds de Recherche du Québec - Santé (Junior 2, Junior 1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, infectious disease burden
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Communicable Diseases, Female, United Kingdom, Humans, Male, Middle Aged, Risk, Incidence, Case-Control Studies, Databases, Factual
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