{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:55:49Z","timestamp":1789779349781,"version":"4.0.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"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. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Heart Failure and Cognitive Impairment are both on the rise and shown to be interlinked. Despite existing reviews delineating a relationship between heart failure and cognitive impairment, the underlying pathophysiology is not researched in great depth. Current literature proposed varying pathophysiological mechanisms and focused heavily on the prevalence of cognitive impairment and treatment interventions such as cardiac rehabilitation. In view of the limitations of previous reviews, this systematic review summarized the best existing evidence concerning different pathophysiological mechanisms behind cognitive impairment in individuals with heart failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight electronic databases including PubMed, Cochrane Library and EMBASE etc., two grey literatures (ProQuest Theses and Dissertations and Mednar) and hand-searching of references were performed using specific criteria regarding population, exposures and outcomes, before duplicate removal and screening using Endnote and Rayyan respectively. JBI critical appraisal tools for non-randomized studies were used for appraisal. Data extraction was performed using two modified forms from JBI Manual for Evidence Synthesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Narrative synthesis was performed to summarize the data from 32 studies. There were three main themes\u2014cognitive impairment due to changes in the brain: brain atrophy, alterations in grey matter and white matter, cerebral alterations, pathway or axis changes, neuroinflammation and hippocampal gene changes; cognitive impairment due to changes in the heart or systemic circulation: inflammation, oxidative stress and changes in serum biomarkers or proteins and the riser rhythm; cognitive impairment due to changes in both the brain and the heart, with seven studies obtaining negative results. There are some limitations such as having non-human studies and large numbers of cross-sectional studies etc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Considering the findings, future research should examine the bi-directional relationship between the brain and the heart as most of the existing research is about the effect of the heart on the brain. By understanding the different pathophysiological mechanisms, the management and prognosis of heart failure patients will be ameliorated. Interventions that slow down or even reverse cognitive impairment can be explored so that these two common issues will not add to the already aggravating disease burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p>This review is registered under PROSPERO. Identifier: CRD42022381359.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1181979","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T10:51:06Z","timestamp":1684839066000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["The pathophysiology of cognitive impairment in individuals with heart failure: a systematic review"],"prefix":"10.3389","volume":"10","author":[{"given":"Reine Sam Shi","family":"Ni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanis Qarissa","family":"Mohamed Raffi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3390\/cells9010242","article-title":"Cellular and molecular differences between HFpEF and HFrEF: a step ahead in an improved pathological understanding","volume":"9","author":"Simmonds","year":"2020","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3390\/jcm5070062","article-title":"Heart failure: diagnosis, management and utilization","volume":"5","author":"Inamdar","year":"2016","journal-title":"J Clin Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1002\/ejhf.1858","article-title":"Epidemiology of heart failure","volume":"22","author":"Groenewegen","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"B4","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.ijcard.2018.04.001","article-title":"Non-cardiac comorbidities in heart failure with reduced, mid-range and preserved ejection fraction","volume":"271","author":"Streng","year":"2018","journal-title":"Int J Cardiol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3389\/fcvm.2021.831734","article-title":"Cognitive impairment in heart failure: landscape, challenges, and future directions","volume":"8","author":"Yang","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3390\/geriatrics5040084","article-title":"Global cognitive impairment prevalence and incidence in community dwelling older adults\u2014a systematic review","volume":"5","author":"Pais","year":"2020","journal-title":"Geriatrics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"687","DOI":"10.2147\/CIA.S73922","article-title":"Mild cognitive impairment and its management older people","volume":"10","author":"Eshkoor","year":"2015","journal-title":"Clin Interv Aging"},{"key":"B8","doi-asserted-by":"publisher","first-page":"17301","DOI":"10.1038\/srep17301","article-title":"Cognitive dysfunction and health-related quality of life among older Chinese","volume":"5","author":"Pan","year":"2015","journal-title":"Sci Rep"},{"key":"B9","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1007\/978-1-4419-1005-9_43","article-title":"Pathophysiology","volume-title":"Encyclopedia of behavioral medicine","author":"Witth\u00f6ft","year":"2013"},{"key":"B10","doi-asserted-by":"publisher","first-page":"838680","DOI":"10.3389\/fcvm.2021.838680","article-title":"Brain imaging changes and related risk factors of cognitive impairment in patients with heart failure","volume":"8","author":"Jiang","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.ijcard.2014.10.087","article-title":"Heart failure and cognitive dysfunction","volume":"178","author":"Ampadu","year":"2015","journal-title":"Int J Cardiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.46658\/JBIMES-20-08","article-title":"Chapter 7: systematic reviews of etiology and risk","author":"Moola","year":"2020","journal-title":"JBI"},{"key":"B13","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"Br Med J"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4155\/fso.15.63","article-title":"Animal models are essential to biological research: issues and perspectives","volume":"1","author":"Barr\u00e9-Sinoussi","year":"2015","journal-title":"Future Sci OA"},{"key":"B15","year":""},{"key":"B16","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan\u2014a web and mobile app for systematic reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst Rev"},{"key":"B17","year":""},{"key":"B18","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1097\/xeb.0000000000000064","article-title":"Conducting systematic reviews of association (etiology): the joanna briggs institute\u2019s approach","volume":"13","author":"Moola","year":"2015","journal-title":"JBI Evid Implement"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1212\/wnl.0000000000000820","article-title":"NT-proBNP, blood pressure, and cognitive decline in the oldest old: the Leiden 85-plus study","volume":"83","author":"van Vliet","year":"2014","journal-title":"Neurology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e12034","DOI":"10.1002\/trc2.12034","article-title":"Cerebral blood flow and cognitive functioning in patients with disorders along the heart\u2013brain axis: cerebral blood flow and the heart\u2013brain axis","volume":"6","author":"Leeuwis","year":"2020","journal-title":"Alzheimers Dement"},{"key":"B21","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1002\/ehf2.12192","article-title":"Atrophy of the parahippocampal gyrus is prominent in heart failure patients without dementia","volume":"4","author":"Meguro","year":"2017","journal-title":"ESC Heart Fail"},{"key":"B22","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.jchf.2018.03.010","article-title":"Cognitive deficits and related brain lesions in patients with chronic heart failure","volume":"6","author":"Frey","year":"2018","journal-title":"JACC Heart Fail"},{"key":"B23","doi-asserted-by":"publisher","first-page":"E29","DOI":"10.1111\/chf.12025","article-title":"Cerebral perfusion is associated with white matter hyperintensities in older adults with heart failure","volume":"19","author":"Alosco","year":"2013","journal-title":"Congest Heart Fail"},{"key":"B24","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1002\/gps.4023","article-title":"Reduced cerebral perfusion predicts greater depressive symptoms and cognitive dysfunction at a 1-year follow-up in patients with heart failure","volume":"29","author":"Alosco","year":"2014","journal-title":"Int J Geriatr Psychiatry"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1002\/ejhf.874","article-title":"Reduced regional cerebral blood flow in patients with heart failure","volume":"19","author":"Roy","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1253\/circj.CJ-16-0367","article-title":"Hippocampal blood flow abnormality associated with depressive symptoms and cognitive impairment in patients with chronic heart failure","volume":"80","author":"Suzuki","year":"2016","journal-title":"Circ J"},{"key":"B27","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1007\/s11357-021-00504-0","article-title":"Cerebral venous congestion exacerbates cerebral microhemorrhages in mice","volume":"44","author":"Nyul-Toth","year":"2022","journal-title":"Geroscience"},{"key":"B28","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s11357-019-00110-1","article-title":"Cerebral venous congestion promotes blood-brain barrier disruption and neuroinflammation, impairing cognitive function in mice","volume":"41","author":"Fulop","year":"2019","journal-title":"Geroscience"},{"key":"B29","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.neuroscience.2019.10.008","article-title":"Dynamic changes in brain glucose metabolism and neuronal structure in rats with heart failure","volume":"424","author":"Yang","year":"2020","journal-title":"Neuroscience"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e014564","DOI":"10.1161\/jaha.119.014564","article-title":"Impaired frontal brain activity in patients with heart failure assessed by near-infrared spectroscopy","volume":"9","author":"Ichijo","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"B31","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ijcard.2020.04.032","article-title":"Cerebral cortical microinfarcts: a novel MRI marker of vascular brain injury in patients with heart failure","volume":"310","author":"Ferro","year":"2020","journal-title":"Int J Cardiol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"5924","DOI":"10.18632\/aging.102150","article-title":"Cognitive impairment in heart failure is associated with altered Wnt signaling in the hippocampus","volume":"11","author":"Toledo","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2291899","DOI":"10.1155\/2021\/2291899","article-title":"Crosstalk between heart failure and cognitive impairment via hsa-miR-933\/RELB\/CCL21 pathway","volume":"2021","author":"Feng","year":"2021","journal-title":"BioMed Res Int"},{"key":"B34","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/chf.12007","article-title":"Elevated levels of interleukin 6 and C-reactive protein associated with cognitive impairment in heart failure","volume":"19","author":"Athilingam","year":"2013","journal-title":"Congest Heart Fail"},{"key":"B35","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1186\/s12872-020-01666-z","article-title":"The relationship between serum uric acid and cognitive function in patients with chronic heart failure","volume":"20","author":"Niu","year":"2020","journal-title":"BMC Cardiovasc Disord"},{"key":"B36","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1002\/ejhf.1442","article-title":"Cognitive impairment in Asian patients with heart failure: prevalence, biomarkers, clinical correlates, and outcomes","volume":"21","author":"Dong","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"B37","doi-asserted-by":"publisher","first-page":"54","DOI":"10.2174\/1874192401307010054","article-title":"Relationship between cognitive function, depression\/anxiety and functional parameters in patients admitted for congestive heart failure","volume":"7","author":"Feola","year":"2013","journal-title":"Open Cardiovasc Med J"},{"key":"B38","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.rec.2017.02.021","article-title":"Bloodstream amyloid-beta (1-40) peptide, cognition, and outcomes in heart failure","volume":"70","author":"Bayes-Genis","year":"2017","journal-title":"Rev Esp Cardiol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1093\/ajh\/hpv086","article-title":"Riser blood pressure pattern is associated with mild cognitive impairment in heart failure patients","volume":"29","author":"Komori","year":"2016","journal-title":"Am J Hypertens"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1002\/ehf2.13986","article-title":"Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure","volume":"9","author":"Traub","year":"2022","journal-title":"ESC Heart Fail"},{"key":"B41","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s13195-022-01087-4","article-title":"Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients","volume":"14","author":"Traub","year":"2022","journal-title":"Alzheimers Res Ther"},{"key":"B42","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1161\/circresaha.119.315813","article-title":"Brain damage with heart failure: cardiac biomarker alterations and gray matter decline","volume":"126","author":"Mueller","year":"2020","journal-title":"Circ Res"},{"key":"B43","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.cardfail.2016.03.006","article-title":"Relationships among cognitive function and cerebral blood flow, oxidative stress, and inflammation in older heart failure patients","volume":"22","author":"Kure","year":"2016","journal-title":"J Card Fail"},{"key":"B44","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.cardfail.2020.02.002","article-title":"Intestinal flora dysbiosis aggravates cognitive dysfunction associated with neuroinflammation in heart failure","volume":"26","author":"Yu","year":"2020","journal-title":"J Card Fail"},{"key":"B45","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1161\/JAHA.117.007694","article-title":"Vascular cognitive impairment linked to brain endothelium inflammation in early stages of heart failure in mice","volume":"7","author":"Adamski","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e63829","DOI":"10.1371\/journal.pone.0063829","article-title":"Increases in the risk of cognitive impairment and alterations of cerebral beta-amyloid metabolism in mouse model of heart failure","volume":"8","author":"Hong","year":"2013","journal-title":"PLoS ONE"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1002\/sctm.16-0382","article-title":"Angiotensin II causes apoptosis of adult hippocampal neural stem cells and memory impairment through the action on AMPK-PGC1 alpha signaling in heart failure","volume":"6","author":"Kim","year":"2017","journal-title":"Stem Cells Transl Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1172\/jci.insight.143141","article-title":"Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure","volume":"6","author":"Baranowski","year":"2021","journal-title":"JCI Insight"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e11900","DOI":"10.15252\/emmm.201911900","article-title":"Epigenetic gene expression links heart failure to memory impairment","volume":"13","author":"Islam","year":"2021","journal-title":"EMBO Mol Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fgene.2021.772343","article-title":"Causal association between heart failure and Alzheimer\u2019s disease: a two-sample bidirectional mendelian randomization study","volume":"12","author":"Duan","year":"2022","journal-title":"Front Genet"},{"key":"B51","doi-asserted-by":"publisher","first-page":"8035","DOI":"10.1007\/s12035-019-01655-0","article-title":"Neurocognitive disorders in heart failure: novel pathophysiological mechanisms underpinning memory loss and learning impairment","volume":"56","author":"Toledo","year":"2019","journal-title":"Mol Neurobiol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"4899688","DOI":"10.1155\/2021\/4899688","article-title":"Cognitive dysfunction after heart disease: a manifestation of the heart-brain axis","volume":"2021","author":"Xu","year":"2021","journal-title":"Oxid Med Cell Longevity"},{"key":"B53","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3390\/biology11020179","article-title":"Cognitive impairment in heart failure-A review","volume":"11","author":"Goh","year":"2022","journal-title":"Biology (Basel)"},{"key":"B54","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1002\/ejhf.319","article-title":"Heart failure as a general pandemic in Asia","volume":"17","author":"Shimokawa","year":"2015","journal-title":"Eur J Heart Fail"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1181979\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T10:51:13Z","timestamp":1684839073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1181979\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":54,"alternative-id":["10.3389\/fcvm.2023.1181979"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2023.1181979","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]},"article-number":"1181979"}}