Key result
Viral infections including SARS-CoV-2, CMV, HCV, and HHV are linked to increased Alzheimer's disease risk.
Why the study?
Viral infections have been implicated in the pathogenesis of neurodegenerative diseases, but evidence linking specific viruses to Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis remains inconclusive.
Do viral infections increase the risk of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis?
Meta-Analysis
Do viral infections increase the risk of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis?
Odds Ratio: 1.41 (95% CI 1.03–1.93)
Specific viral infections, including CMV, SARS-CoV-2, HCV, HHV, and HBV, are associated with an increased risk of developing Alzheimer's and Parkinson's diseases, but not amyotrophic lateral sclerosis.
Select viruses linked to higher AD/PD risk but not ALS; leaves open causality and warrants prospective confirmation before clinical consideration.
BACKGROUND: Viral infections have been implicated in the pathogenesis of neurodegenerative diseases (NDs); however, evidence linking specific viruses to Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) remains inconclusive. This study conducted a meta-analysis and systematic review to investigate these associations. METHODS: Thorough searches were conducted across Embase, PubMed, Cochrane Library, Web of Science and Scopus until May 18, 2025, to identify observational studies investigating the relationship between viral infections and the risk of NDs, including AD, PD, and ALS. Meta-analyses were executed using a random-effects model with Stata MP18.0. RESULTS: A total of 34,417 articles were identified, of which 73 met the eligibility criteria for inclusion in the meta-analysis, and 48 were included in the systematic review. The analysis demonstrated that infections with cytomegalovirus (CMV) (odds ratio [OR] = 1.41; 95% confidence interval [CI]: 1.03, 1.93), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (OR = 1.88; 95% CI: 1.53, 2.32), hepatitis C virus (HCV) (OR = 1.39; 95% CI: 1.14, 1.69), and human herpesvirus (HHV) (OR = 1.24; 95% CI: 1.02, 1.51) were associated with an increased risk of AD. Regarding PD, infections with hepatitis B virus (HBV) (OR = 1.18; 95% CI: 1.04, 1.35) and HCV (OR = 1.29; 95% CI: 1.18, 1.41) were identified as risk factors. Conversely, no significant correlation was found between any viral infection and the risk of ALS. CONCLUSION: This meta-analysis supports the role of select viral infections in AD and PD pathogenesis. However, no association was found between viral infections and ALS, warranting further large, multicenter, and longitudinal studies to elucidate mechanisms and confirm causality.
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Yin et al. (2025) conducted a meta-analysis in Neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis). Viral infections (e.g., CMV, SARS-CoV-2, HCV, HHV, HBV) vs. Individuals with no evidence of the studied viral infections was evaluated on Risk of Alzheimer's disease associated with cytomegalovirus (CMV) infection (OR 1.41, 95% CI 1.03, 1.93). Infections with cytomegalovirus (OR 1.41), SARS-CoV-2 (OR 1.88), hepatitis C virus (OR 1.39), and human herpesvirus (OR 1.24) were associated with an increased risk of Alzheimer's disease.
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