TY - JOUR
T1 - Herpes Labialis, Chlamydophila pneumoniae, Helicobacter pylori, and Cytomegalovirus Infections and Risk of Dementia
T2 - The Framingham Heart Study
AU - Zilli, Eduardo Marques
AU - O'Donnell, Adrienne
AU - Salinas, Joel
AU - Aparicio, Hugo J.
AU - Gonzales, Mitzi Michelle
AU - Jacob, Mini
AU - Beiser, Alexa
AU - Seshadri, Sudha
AU - Lövheim, Hugo
N1 - Publisher Copyright:
© 2021 - IOS Press. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Dementia
KW - Framingham
KW - Herpes labialis
KW - Viral infections
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U2 - 10.3233/JAD-200957
DO - 10.3233/JAD-200957
M3 - Article
C2 - 34057145
AN - SCOPUS:85111395106
SN - 1387-2877
VL - 82
SP - 593
EP - 605
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -