{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:04:33Z","timestamp":1785881073627,"version":"3.56.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011490","name":"College of Veterinary Medicine, North Carolina State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011490","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016230","name":"Steven and Alexandra Cohen Foundation","doi-asserted-by":"publisher","award":["53d1459"],"award-info":[{"award-number":["53d1459"]}],"id":[{"id":"10.13039\/100016230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Mild Cognitive Impairment (MCI) is a neurological disorder at the transition between normal cognitive decline and dementia. Despite the potential role of neuroinflammation in the pathogenesis of MCI, infectious triggers remain mostly unknown. Infection with <jats:italic>Bartonella<\/jats:italic> spp., a zoonotic bacterium, has recently been associated with diffuse neurological and psychiatric symptoms. Given the preferential endothelial localization of <jats:italic>Bartonella<\/jats:italic> spp. and the role of vascular changes in neurocognitive decline, we hypothesized that there is an association between <jats:italic>Bartonella<\/jats:italic> spp. infection and pathologically accelerated decline in cognitive function in aging. To test this hypothesis, we collected serological and molecular markers of past and present <jats:italic>Bartonella<\/jats:italic> spp. infection in a sample of older people with and without MCI. Samples were processed in a blinded way to exclude laboratory biases. Contrary to our hypothesis, people with MCI were not more likely than people without MCI to have an active <jats:italic>Bartonella<\/jats:italic> spp. infection as measured by droplet digital PCR (<jats:italic>p<\/jats:italic> = 0.735) and quantitative PCR (<jats:italic>p<\/jats:italic> = 1). In addition, there was no significant difference in positive serological results between cases and controls (<jats:italic>p<\/jats:italic> = 0.461). Overall, higher-than-expected active <jats:italic>Bartonella<\/jats:italic> spp. infection (37% by ddPCR) and seroreactivity (71% by indirect fluorescent antibody assay) were found in people without MCI. Conclusions require caution, as our study was limited by the small number of cases with MCI. Overall, our results identified a higher than previously recognized rate of exposure and infection with <jats:italic>Bartonella spp<\/jats:italic>. in this older study population but does not support a specific role for such infection in MCI.<\/jats:p>","DOI":"10.1371\/journal.pone.0307060","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T18:41:03Z","timestamp":1724352063000},"page":"e0307060","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bartonella spp. infection in people with Mild Cognitive Impairment: A pilot study"],"prefix":"10.1371","volume":"19","author":[{"given":"Verina","family":"Guirguis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pupillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siena","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chance E.","family":"Liedig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richardo G.","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"Breitschwerdt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3724-5621","authenticated-orcid":true,"given":"Flavio","family":"Frohlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"issue":"10","key":"pone.0307060.ref001","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1212\/WNL.0b013e3181f11d85","article-title":"Prevalence of mild cognitive impairment is higher in men","volume":"75","author":"RC Petersen","year":"2010","journal-title":"Neurology"},{"issue":"4","key":"pone.0307060.ref002","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1600-0447.2008.01326.x","article-title":"Rate of progression of mild cognitive impairment to dementia\u2013meta-analysis of 41 robust inception cohort studies.","volume":"119","author":"AJ Mitchell","year":"2009","journal-title":"Acta Psychiatr Scand"},{"issue":"8","key":"pone.0307060.ref003","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.18632\/aging.101924","article-title":"Identification of inflammatory and vascular markers associated with mild cognitive impairment.","volume":"11","author":"XN Shen","year":"2019","journal-title":"Aging"},{"issue":"5","key":"pone.0307060.ref004","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1136\/jnnp-2018-319148","article-title":"Inflammatory markers in Alzheimer\u2019s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies","volume":"90","author":"XN Shen","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0307060.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arr.2019.01.002","article-title":"Neuroinflammation in mild cognitive impairment and Alzheimer\u2019s disease: A meta-analysis.","volume":"50","author":"S Bradburn","year":"2019","journal-title":"Ageing Res Rev."},{"issue":"6","key":"pone.0307060.ref006","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","article-title":"Neuroinflammation in Alzheimer\u2019s disease: Current evidence and future directions.","volume":"12","author":"V Calsolaro","year":"2016","journal-title":"Alzheimers Dement J Alzheimers Assoc."},{"key":"pone.0307060.ref007","doi-asserted-by":"crossref","first-page":"773","DOI":"10.3389\/fpsyt.2020.00773","article-title":"The Challenge of Assessing Mild Neuroinflammation in Severe Mental Disorders","volume":"11","author":"K. 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Koesling","year":"2001","journal-title":"J Immunol"},{"key":"pone.0307060.ref026","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jviromet.2015.08.014","article-title":"Optimization of Droplet Digital PCR from RNA and DNA extracts with direct comparison to RT-qPCR: Clinical implications for quantification of Oseltamivir-resistant subpopulations","volume":"224","author":"SC Taylor","year":"2015","journal-title":"J Virol Methods"},{"key":"pone.0307060.ref027","doi-asserted-by":"crossref","first-page":"106022","DOI":"10.1016\/j.mimet.2020.106022","article-title":"Development and validation of a droplet digital PCR assay for the detection and quantification of Bartonella species within human clinical samples","volume":"176","author":"RG Maggi","year":"2020","journal-title":"J Microbiol Methods"},{"issue":"2","key":"pone.0307060.ref028","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/08927936.2021.1986259","article-title":"Pet Caretaking and Risk of Mild 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Dehio","year":"2004","journal-title":"Annu Rev Microbiol"},{"issue":"1","key":"pone.0307060.ref032","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1128\/CMR.05009-11","article-title":"Intruders below the Radar: Molecular Pathogenesis of Bartonella spp.","volume":"25","author":"A Harms","year":"2012","journal-title":"Clin Microbiol Rev"},{"issue":"8","key":"pone.0307060.ref033","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1046\/j.1365-4362.2002.01489.x","article-title":"Skin manifestations of Bartonella infections.","volume":"41","author":"CA Chian","year":"2002","journal-title":"Int J Dermatology."},{"issue":"3","key":"pone.0307060.ref034","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1542\/peds.100.3.403","article-title":"Central Nervous System Infection Associated With Bartonella quintana: A Report of Two Cases","volume":"100","author":"JH Parrott","year":"1997","journal-title":"Pediatrics"},{"issue":"9","key":"pone.0307060.ref035","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1001\/archneur.58.9.1357","article-title":"Concurrent Infection of the Central Nervous System by Borrelia burgdorferi and Bartonella henselae: Evidence for a Novel Tick-borne Disease Complex","volume":"58","author":"E Eskow","year":"2001","journal-title":"Archives of Neurology"},{"issue":"3","key":"pone.0307060.ref036","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3904\/kjim.2016.010","article-title":"The seroprevalence of Bartonella henselae in healthy adults in Korea","volume":"32","author":"HY Kwon","year":"2017","journal-title":"Korean J Intern Med"},{"issue":"3","key":"pone.0307060.ref037","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3390\/pathogens9030189","article-title":"Bartonella spp. Prevalence (Serology, Culture, and PCR) in Sanitary Workers in La Rioja Spain.","volume":"9","author":"A Portillo","year":"2020","journal-title":"Pathogens"},{"issue":"5","key":"pone.0307060.ref038","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/ni.2588","article-title":"Understanding immunosenescence to improve responses to vaccines","volume":"14","author":"JJ Goronzy","year":"2013","journal-title":"Nat Immunol"},{"issue":"6","key":"pone.0307060.ref039","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1093\/cid\/ciab696","article-title":"Mortality, Length of Stay, and Healthcare Costs Associated With Multidrug-Resistant Bacterial Infections Among Elderly Hospitalized Patients in the United States","volume":"74","author":"RE Nelson","year":"2022","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"issue":"8","key":"pone.0307060.ref040","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1590\/S0074-02762005000800006","article-title":"Antibodies to Rickettsia rickettsii, Rickettsia typhi, Coxiella burnetii, Bartonella henselae, Bartonella quintana, and Ehrlichia chaffeensis among healthy population in Minas Gerais, Brazil","volume":"100","author":"Brigatte ME Costa PSGD","year":"2005","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"9","key":"pone.0307060.ref041","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1128\/jcm.34.9.2270-2274.1996","article-title":"Serological cross-reactions between Bartonella quintana, Bartonella henselae, and Coxiella burnetii","volume":"34","author":"B La Scola","year":"1996","journal-title":"J Clin Microbiol"},{"issue":"6","key":"pone.0307060.ref042","doi-asserted-by":"crossref","first-page":"e0011336","DOI":"10.1371\/journal.pntd.0011336","article-title":"Comparison of molecular methods for Bartonella henselae detection in blood donors","volume":"17","author":"MR Drummond","year":"2023","journal-title":"PLOS Neglected Tropical Diseases"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T18:42:00Z","timestamp":1724352120000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307060"}},"subtitle":[],"editor":[{"given":"Michael F.","family":"Minnick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0307060","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,22]]}}}