The association between herpes simplex virus type 1 infection and Alzheimer's disease.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies (assessed via Newcastle-Ottawa Scale)
PubMed 33317741 · doi:10.1016/j.jocn.2020.10.044
What was done
Authors searched PubMed, Embase, and Cochrane databases for studies published between 1990 and 2020 evaluating the association between herpes simplex virus type 1 (HSV-1) infection and Alzheimer's disease (AD). Quality was assessed using the Newcastle-Ottawa Scale (NOS). Random-effects models were used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses stratified by APOE ε4 status, NOS score, and method of AD confirmation.
What was found
Across 21 studies, HSV-1 infection was significantly associated with AD overall (pooled OR 1.40, 95% CI: 1.13–1.75; I² = 3%, P = 0.42). In subgroup analyses, statistically significant associations were maintained only in high NOS score studies (OR 1.51, 95% CI: 1.10–2.06) and clinically diagnosed AD cohorts (OR 1.47, 95% CI: 1.16–1.87). Subgroup findings were not statistically significant in APOE ε4-positive individuals (OR 0.75, 95% CI: 0.24–2.37), APOE ε4-negative individuals (OR 0.85, 95% CI: 0.61–1.17), moderate NOS studies (OR 1.23, 95% CI: 0.85–1.76), or autopsy-confirmed AD cases (OR 1.20, 95% CI: 0.77–1.87).
Why it matters
This meta-analysis aggregates observational evidence on the HSV-1 hypothesis in AD, demonstrating an overall pooled association driven predominantly by clinically diagnosed rather than neuropathologically confirmed cases.
Limits
The abstract does not report total participant counts. Because it compiles observational studies, it cannot establish causality. The overall association loses statistical significance when limited to gold-standard autopsy-confirmed cases and reverses direction below 1.0 without statistical significance in both APOE ε4-stratified groups.
Cited by
- partial Herpes simplex virus type 1 (HSV-1) cold sores are associated with an increased risk of developing Alzheimer's disease.