{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:23:53Z","timestamp":1791667433776,"version":"4.3.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Hum. Neurosci."],"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Brain fog is associated with significant morbidity and reduced productivity and gained increasing attention after COVID-19. However, this subjective state has not been systematically characterised.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterise self-reported brain fog.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>We systematically studied the cross-sectional associations between 29 <jats:italic>a priori<\/jats:italic> variables with the presence of \u201cbrain fog.\u201d The variables were grouped into four categories: demographics, symptoms and functional impairments, comorbidities and potential risk factors (including lifestyle factors), and cognitive score. Univariate methods determined the correlates of brain fog, with long-COVID and non-long-COVID subgroups. XGBoost machine learning model retrospectively characterised subjective brain fog. Bonferroni-corrected statistical significance was set at 5%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Digital application for remote data collection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>25,796 individuals over the age of 18 who downloaded and completed the application.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>7,280 of 25,796 individuals (28.2%) reported experiencing brain fog, who were generally older (mean brain fog 35.7\u2009\u00b1\u200911.9\u2009years vs. 32.8\u2009\u00b1\u200911.6\u2009years, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001) and more likely to be female (OR\u2009=\u20091.2, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001). Associated symptoms and functional impairments included d<jats:italic>ifficulty focusing or concentrating<\/jats:italic> (OR\u2009=\u20093.3), <jats:italic>feeling irritable<\/jats:italic> (OR\u2009=\u20091.6), <jats:italic>difficulty relaxing<\/jats:italic> (OR\u2009=\u20091.2, all <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001), <jats:italic>difficulty following conversations<\/jats:italic> (OR\u2009=\u20092.2), <jats:italic>remembering appointments<\/jats:italic> (OR\u2009=\u20091.9), <jats:italic>completing paperwork<\/jats:italic> and performing <jats:italic>mental arithmetic<\/jats:italic> (ORs\u2009=\u20091.8, all <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001). Comorbidities included long-COVID-19 (OR\u2009=\u20093.8, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001), concussions (OR\u2009=\u20092.4, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001), and higher migraine disability assessment scores (MIDAS) (+34.1%, all <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001). Cognitive scores were marginally lower with brain fog (\u22120.1 std., <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001). XGBoost achieved a training accuracy of 85% with cross-validated accuracy of 74%, and the features most predictive of brain fog in the model were difficulty focusing and following conversations, long-COVID, and severity of migraines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and relevance<\/jats:title><jats:p>This is the largest study characterising subjective brain fog as an impairment of concentration associated with functional impairments in activities of daily living. Brain fog was particularly associated with a history of long-COVID-19, migraines, concussion, and with 0.1 standard deviations lower cognitive scores, especially on modified Stroop testing, suggesting impairments in the ability to inhibit cognitive interference. Further prospective studies in unselected brain fog sufferers should explore the full spectrum of brain fog symptoms to differentiate it from its associated conditions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnhum.2024.1409250","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T19:28:00Z","timestamp":1718134080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Subjective brain fog: a four-dimensional characterization in 25,796 participants"],"prefix":"10.3389","volume":"18","author":[{"given":"Ali","family":"Alim-Marvasti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Ciocca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan","family":"Kuleindiren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamzah","family":"Selim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Mahmud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1029810","DOI":"10.3389\/fdgth.2022.1029810","article-title":"Validation of a rapid remote digital test for impaired cognition using clinical dementia rating and mini-mental state examination: an observational research study","volume":"4","author":"Alim-Marvasti","year":"","journal-title":"Front. Digit. Health"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/02699052.2022.2158229","article-title":"Hierarchical clustering of prolonged post-concussive symptoms after 12 months: symptom-centric analysis and association with functional impairments","author":"Alim-Marvasti","year":"","journal-title":"Brain Inj."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1002\/jmv.27404","article-title":"Long COVID syndrome-associated brain fog","volume":"94","author":"Asadi-Pooya","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1046\/j.1526-4610.2003.03068.x","article-title":"\"Assessment of migraine disability using the migraine disability assessment (MIDAS) questionnaire: a comparison of chronic migraine with episodic migraine.\" headache: the journal of Head and face","volume":"43","author":"Bigal","year":"2003","journal-title":"Pain"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1038\/s41591-021-01433-3","article-title":"Long COVID in a prospective cohort of home-isolated patients","volume":"27","author":"Blomberg","year":"2021","journal-title":"Nat. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.jpsychores.2005.10.020","article-title":"The brief illness perception questionnaire","volume":"60","author":"Broadbent","year":"2006","journal-title":"J. Psychosom. Res."},{"key":"ref7","volume-title":"Delirium: acute confusional states in palliative medicine","author":"Caraceni","year":"2011"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"12816","DOI":"10.3390\/ijerph191912816","article-title":"Brain fog and quality of life at work in non-hospitalized patients after COVID-19","volume":"19","author":"Chatys-Bogacka","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref9","author":"Chen","year":"2016"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"101019","DOI":"10.1016\/j.eclinm.2021.101019","article-title":"Characterizing long COVID in an international cohort: 7 months of symptoms and their impact","volume":"38","author":"Davis","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref9001","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16084","article-title":"Unraveling brain fog in post\u2010COVID syndrome: relationship between subjective cognitive complaints and cognitive function, fatigue, and neuropsychiatric symptoms","author":"Delgado\u2010Alonso","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1093\/brain\/awac384","article-title":"Multimodal neuroimaging in post-COVID syndrome and correlation with cognition","volume":"146","author":"D\u00edez-Cirarda","year":"2023","journal-title":"Brain"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"204","DOI":"10.3389\/fnagi.2022.804937","article-title":"COVCOG 2: cognitive and memory deficits in long COVID: a second publication from the COVID and cognition study","volume":"14","author":"Guo","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"101044","DOI":"10.1016\/j.eclinm.2021.101044","article-title":"Cognitive deficits in people who have recovered from COVID-19","volume":"39","author":"Hampshire","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.eswa.2019.06.064","article-title":"Combining hierarchical clustering approaches using the PCA method","volume":"137","author":"Jafarzadegan","year":"2019","journal-title":"Expert Syst. Appl."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e00911","DOI":"10.1002\/prp2.911","article-title":"\u201cLONG COVID\u201d\u2014a hypothesis for understanding the biological basis and pharmacological treatment strategy","volume":"10","author":"Jarrott","year":"2022","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.3390\/jcm11123440","article-title":"Comprehensive clinical characterisation of brain fog in adults reporting long COVID symptoms","volume":"11","author":"Jennings","year":"2022","journal-title":"J. Clin. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e31209","DOI":"10.2196\/31209","article-title":"Optimizing existing mental health screening methods in a dementia screening and risk factor app: observational machine learning study","volume":"6","author":"Kuleindiren","year":"2022","journal-title":"JMIR Form. Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3928\/02793695-20211013-01","article-title":"Brain fog: a bit of clarity regarding etiology, prognosis, and treatment","volume":"59","author":"Kverno","year":"2021","journal-title":"J. Psychosoc. Nurs. Ment. Health Serv."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"4640","DOI":"10.1007\/s00415-023-11913-w","article-title":"Characterizing long-COVID brain fog: a retrospective cohort study","volume":"270","author":"Lam","year":"2023","journal-title":"J. Neurol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1111\/apt.12852","article-title":"\u2018Brain fog\u2019 and coeliac disease\u2013evidence for its existence","volume":"40","author":"Lebwohl","year":"2014","journal-title":"Wiley"},{"key":"ref21","first-page":"219","article-title":"Illness representations and coping with health threats","volume-title":"Handbook of Psychology and Health","author":"Leventhal","year":"2020"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1111\/apt.12867","article-title":"\u2018Brain Fog\u2019and coeliac disease\u2013evidence for its existence: authors\u2019 reply","volume":"40","author":"Lichtwark","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1111\/j.1526-4610.2001.01156.x","article-title":"\"Clinical utility of an instrument assessing migraine disability: the migraine disability assessment (MIDAS) questionnaire.\" headache: the journal of Head and face","volume":"41","author":"Lipton","year":"2001","journal-title":"Pain"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1001\/jamaneurol.2022.0461","article-title":"One-year trajectory of cognitive changes in older survivors of COVID-19 in Wuhan, China: a longitudinal cohort study","volume":"79","author":"Liu","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e005427","DOI":"10.1136\/bmjgh-2021-005427","article-title":"Characterising long COVID: a living systematic review","volume":"6","author":"Michelen","year":"2021","journal-title":"BMJ Glob. Health"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s42399-022-01352-5","article-title":"Brain fog as a long-term sequela of COVID-19","volume":"5","author":"Nouraeinejad","year":"2022","journal-title":"SN Compr. Clin. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1007\/s11912-013-0307-7","article-title":"Clearing the air: a review of our current understanding of \u201cchemo fog\u201d","volume":"15","author":"O\u2019Farrell","year":"2013","journal-title":"Curr. Oncol. Rep."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3389\/fphys.2013.00063","article-title":"Caught in the thickness of brain fog: exploring the cognitive symptoms of chronic fatigue syndrome","volume":"4","author":"Ocon","year":"2013","journal-title":"Front. Physiol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1097\/00006842-200207000-00007","article-title":"Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial","volume":"64","author":"Petrie","year":"2002","journal-title":"Psychosom. Med."},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1136\/bmjinnov-2021-000780","article-title":"Preliminary validation study of the Mindset4Dementia application: assessing remote collection of dementia risk factors and cognitive performance","volume":"7","author":"Rifkin-Zybutz","year":"2021","journal-title":"BMJ Innov."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s10286-013-0212-z","article-title":"What is brain fog? An evaluation of the symptom in postural tachycardia syndrome","volume":"23","author":"Ross","year":"2013","journal-title":"Clin. Auton. Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"557","DOI":"10.3389\/fpsyg.2017.00557","article-title":"The stroop color and word test","volume":"8","author":"Scarpina","year":"2017","journal-title":"Front. Psychol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.5664\/jcsm.7478","article-title":"A new single-item sleep quality scale: results of psychometric evaluation in patients with chronic primary insomnia and depression","volume":"14","author":"Snyder","year":"2018","journal-title":"J. Clin. Sleep Med."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1126\/science.abm2052","article-title":"Nervous system consequences of COVID-19","volume":"375","author":"Spudich","year":"2022","journal-title":"Science"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1212\/WNL.53.5.988","article-title":"An international study to assess reliability of the migraine disability assessment (MIDAS) score","volume":"53","author":"Stewart","year":"1999","journal-title":"Neurology"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1037\/h0054651","article-title":"Studies of interference in serial verbal reactions","volume":"18","author":"Stroop","year":"1935","journal-title":"J. Exp. Psychol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e1003773","DOI":"10.1371\/journal.pmed.1003773","article-title":"Incidence, co-occurrence, and evolution of long-COVID features: a 6-month retrospective cohort study of 273, 618 survivors of COVID-19","volume":"18","author":"Taquet","year":"2021","journal-title":"PLoS Med."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1038\/s41591-023-02525-y","article-title":"Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization","volume":"29","author":"Taquet","year":"2023","journal-title":"Nat. Med."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1080\/08870449608400270","article-title":"The illness perception questionnaire: a new method for assessing the cognitive representation of illness","volume":"11","author":"Weinman","year":"1996","journal-title":"Psychol. Health"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1002\/joa3.12325","article-title":"Brain fog in postural tachycardia syndrome: an objective cerebral blood flow and neurocognitive analysis","volume":"36","author":"Wells","year":"2020","journal-title":"J. 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