{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T23:01:27Z","timestamp":1788735687422,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Graduate Program in Health Sciences at the Faculty of Medicine of UFG and IF Goiano","award":["ES\/T008822\/11"],"award-info":[{"award-number":["ES\/T008822\/11"]}]},{"DOI":"10.13039\/501100000269","name":"Economic and Social Research Council","doi-asserted-by":"publisher","award":["ES\/T008822\/11"],"award-info":[{"award-number":["ES\/T008822\/11"]}],"id":[{"id":"10.13039\/501100000269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Dementia and cognitive decline are highly prevalent in later life and are growing public health concerns worldwide due to the increasing aging population. Individuals diagnosed with dementia have reduced mental function, resulting in social and cognitive skill deficits, increased dependence, and reduced autonomy\u2014all of which are conditions associated with higher mortality rates. This systematic review aims to assess the effectiveness of treating dementia and cognitive decline with methylfolate. The main outcomes analyzed will be dementia and changes in cognitive function measured by different instruments in older adults treated with methylfolate. Secondary outcomes, such as inflammatory markers, plasma folic-acid levels, and total homocysteine, will also be assessed. Methods and Analysis: This study will be carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This protocol is registered in the International Prospective Registry of Systematic Reviews, under the code CRD42021275755. We will include clinical trials conducted with older adults diagnosed with dementia or cognitive decline and treated with folic acid. The searches will be conducted on the PubMed, Scopus, and Embase databases, and the articles will be selected by reading their titles and abstracts first, followed by the full text. The quality of the selected studies will be assessed using GRADE and the risk of bias will be assessed using the Downs-and-Black method. Ethics and Dissemination: The results will be presented at scientific conferences and disseminated by publishing a scientific article in an international English-language journal. We hope to find robust and significant evidence regarding the effectiveness of methylfolate supplementation in improving dementia symptoms and cognitive decline among older adults. By systematizing this evidence and possibly performing a meta-analysis study, we expect to significantly contribute to the treatment of this health problem, reduce mortality, and improve the quality of life and health of this population, boosting the development of medical protocols capable of reducing the financial effects of public health.<\/jats:p>","DOI":"10.3390\/jcm12093075","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T02:31:05Z","timestamp":1682303465000},"page":"3075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Effects of Methylfolate on Cognitive Decline and Dementia: A Protocol for Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5305-0613","authenticated-orcid":false,"given":"Le\u00edcia Iris de Assun\u00e7\u00e3o","family":"Prado","sequence":"first","affiliation":[{"name":"Postgraduate Program in Health Sciences, Faculty of Medicine, Federal University of Goi\u00e1s, Goiania 74605-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1526-7440","authenticated-orcid":false,"given":"Ana L\u00facia","family":"Junger","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Faculty of Medicine, Federal University of Goi\u00e1s, Goiania 74605-050, Brazil"},{"name":"Goiano Federal Institute, Ceres 76300-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-9058","authenticated-orcid":false,"given":"Leonardo Ferreira","family":"Caixeta","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Faculty of Medicine, Federal University of Goi\u00e1s, Goiania 74605-050, Brazil"},{"name":"Department of Neurology, School of Medicine, Federal University of Goi\u00e1s, Goiania 74690-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1482-0718","authenticated-orcid":false,"given":"Matias","family":"Noll","sequence":"additional","affiliation":[{"name":"Goiano Federal Institute, Ceres 76300-000, Brazil"},{"name":"Departament of Sports Science and Clinical Biomechanics, University of Southernz Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4099-4762","authenticated-orcid":false,"given":"Cesar de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Public Health, Institute of Epidemiology & Health Care, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8839-4520","authenticated-orcid":false,"given":"\u00c9rika Aparecida","family":"Silveira","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Faculty of Medicine, Federal University of Goi\u00e1s, Goiania 74605-050, Brazil"},{"name":"Department of Epidemiology & Public Health, Institute of Epidemiology & Health Care, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1474-4422(18)30403-4","article-title":"Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Nichols","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet Commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1177\/153331750201700210","article-title":"Co-morbidity associated with dementia","volume":"17","author":"Sanderson","year":"2002","journal-title":"Am. 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