Herpes Labialis, Chlamydophila pneumoniae, Helicobacter pylori, and Cytomegalovirus Infections and Risk of Dementia: The Framingham Heart Study

Article type: Research Article

Authors: Zilli, Eduardo Marques^{a; *} | O’Donnell, Adrienne^b | Salinas, Joel^c | Aparicio, Hugo J.^{d; e} | Gonzales, Mitzi Michelle^a | Jacob, Mini^a | Beiser, Alexa^{b; d} | Seshadri, Sudha^{a; b; d; e}

Affiliations: [a] Glenn Biggs Institute of Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, TX, USA | [b] Boston University School of Public Health, Boston, MA, USA | [c] New York University Grossman School of Medicine, New York, NY, USA | [d] Boston University School of Medicine, Boston, MA, USA | [e] Framingham Heart Study, Framingham, MA, USA

Correspondence: [*] Correspondence to: Eduardo Marques Zilli, Glenn Biggs Institute of Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Tel.: +1 210 450 9960; E-mail: marqueszilli@uthscsa.edu.

Abstract: Background:An association between chronic infectious diseases and development of dementia has been suspected for decades, based on the finding of pathogens in postmortem brain tissue and on serological evidence. However, questions remain regarding confounders, reverse causality, and how accurate, reproducible and generalizable those findings are. Objective:Investigate whether exposure to Herpes simplex (manifested as herpes labialis), Chlamydophila pneumoniae (C. pneumoniae), Helicobacter pylori (H. pylori), and cytomegalovirus (CMV) modifies the risk of dementia in a populational cohort. Methods:Questionnaires regarding incidence of herpes infections were administered to Original Framingham Study participants (n = 2,632). Serologies for C. pneumoniae, H. pylori, and CMV were obtained in Original (n = 2,351) and Offspring cohort (n = 3,687) participants. Participants are under continuous dementia surveillance. Brain MRI and neuropsychological batteries were administered to Offspring participants from 1999–2005. The association between each infection and incident dementia was tested with Cox models. Linear models were used to investigate associations between MRI or neuropsychological parameters and serologies. Results:There was no association between infection serologies and dementia incidence, total brain volume, and white matter hyperintensities. Herpes labialis was associated with reduced 10-year dementia risk (HR 0.66, CI 0.46–0.97), but not for the duration of follow-up. H. pylori antibodies were associated with worse global cognition (β –0.14, CI –0.22, –0.05). Conclusion:We found no association between measures of chronic infection and incident dementia, except for a reduction in 10-year dementia risk for patients with herpes labialis. This unexpected result requires confirmation and further characterization, concerning antiviral treatment effects and capture of episodes.

Keywords: Alzheimer’s disease, dementia, Framingham, herpes labialis, viral infections

DOI: 10.3233/JAD-200957

Journal: Journal of Alzheimer's Disease, vol. 82, no. 2, pp. 593-605, 2021