Infectious Disease Burden and the Risk of Alzheimer’s Disease: A Population-Based Study

Article type: Research Article

Authors: Douros, Antonios^{a; b; c; d} | Santella, Christina^c | Dell’Aniello, Sophie^c | Azoulay, Laurent^{b; c; e} | Renoux, Christel^{b; c; f} | Suissa, Samy^{a; b; c} | Brassard, Paul^{a; b; c; *}

Affiliations: [a] Department of Medicine, McGill University, Montreal, QC, Canada | [b] Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada | [c] Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, QC, Canada | [d] Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Berlin, Germany | [e] Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada | [f] Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada

Correspondence: [*] Correspondence to: Paul Brassard, MD, MSc, Centre for Clinical Epidemiology, Lady Davis Institute, 3755 Chemin de la Cote St-Catherine, H-424, Montréal, QC H3T1E2, Canada. Tel.: +1 514 340 7563; E-mail: paul.brassard@mcgill.ca.

Abstract: 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.

Keywords: Alzheimer’s disease, dementia, epidemiology, infection, neurodegenerative diseases

DOI: 10.3233/JAD-201534

Journal: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 329-338, 2021