Hospital-treated prevalent infections, the plasma proteome and incident dementia among UK older adults
May A. Beydoun,
Hind A. Beydoun,
Nicole Noren Hooten,
Osorio Meirelles,
Zhiguang Li,
Ziad W. El-Hajj,
Jordan Weiss,
Christian A. Maino Vieytes,
Lenore J. Launer,
Michele K. Evans,
Alan B. Zonderman
Affiliations
May A. Beydoun
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA; Corresponding author
Hind A. Beydoun
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA; AT Augusta Military Medical Center, Fort Belvoir, VA 22060, USA
Nicole Noren Hooten
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA
Osorio Meirelles
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA
Zhiguang Li
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA
Ziad W. El-Hajj
Department of Biology, McGill University, Montreal, QC, Canada
Jordan Weiss
Stanford Center on Longevity, Stanford University, Palo Alto, CA 94305, USA
Christian A. Maino Vieytes
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA
Lenore J. Launer
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA
Michele K. Evans
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA
Alan B. Zonderman
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Intramural Research Program, NIA/NIH/IRP, Baltimore, MD 21224, USA
Summary: The plasma proteome can mediate the association of hospital-treated infections with dementia incidence. We screened up to 37,269 UK Biobank participants aged 50–74 years for the presence of a prevalent hospital-treated infection, subsequently tested as a predictor for ≤1,463 plasma proteins and dementia incidence. Four-way decomposition models decomposed infection-dementia total effect into pure mediation, pure interaction, neither or both through the plasma proteome. Hospital-treated infections increased dementia two-fold. The strongest mediation effect was through the growth differentiation factor 15 (GDF15) protein. Top 17 proteomic mediators explained collectively 5% of the total effect, while pathway analysis of all mediators (k = 221 plasma proteins) revealed top pathways including the immune system, signal transduction, metabolism, disease and metabolism of proteins, with the GDF15 cluster reflecting most strongly the “transmembrane receptor protein tyrosine kinase signaling pathway”. The association of hospital-treated infections with dementia was partially mediated through GDF15 and other plasma proteomic markers.
