{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:12:29Z","timestamp":1779340349957,"version":"3.51.4"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"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. Public Health"],"abstract":"\n Background<\/jats:title>\n Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia, with annual conversion rates to Alzheimer's disease (AD) or all-cause dementia estimated at 10%\u221215%. The role of depression as a prognostic factor for dementia progression remains unclear. This systematic review and meta-analysis aimed to clarify the association between depression and risk of conversion from MCI to AD and all-cause dementia.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a systematic review and meta-analysis of longitudinal cohort studies following PRISMA 2020 guidelines. PubMed, PsycINFO, Web of Science, and Scopus were searched. Eligible studies included adults with MCI, depression assessed by clinical diagnosis or validated scales, and reported hazard ratios (HRs) for progression to dementia. Random-effects meta-analyses were performed for unadjusted and adjusted HRs. Risk of bias was assessed using the Newcastle\u2013Ottawa Scale, and certainty of evidence was evaluated with GRADE.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Seventeen studies were included, with follow-up ranging from 6 months to 12 years. In unadjusted analyses, baseline depression was associated with increased risk of progression overall (HR 1.66, 95% CI 1.22\u20132.26); however, heterogeneity across studies was high (\n I<\/jats:italic>\n 2<\/jats:sup>\n = 99.1%), limiting confidence in the pooled estimate. The association was significant for progression to AD (HR 1.57, 95% CI 1.15\u20132.15\n ; I<\/jats:italic>\n 2<\/jats:sup>\n = 99.4%), but not for all-cause dementia (HR 1.95, 95% CI 0.85\u20134.48;\n I<\/jats:italic>\n 2<\/jats:sup>\n = 90%). In adjusted analyses, depression remained associated with increased progression risk overall (HR 1.21, 95% CI 1.05\u20131.39), with high heterogeneity (\n I<\/jats:italic>\n 2<\/jats:sup>\n = 99.8%). The association was statistically significant for all-cause dementia (HR 1.24, 95% CI 1.01\u20131.52;\n I<\/jats:italic>\n 2<\/jats:sup>\n = 78.8%), but not for AD (HR 1.18, 95% CI 0.95\u20131.47;\n I<\/jats:italic>\n 2<\/jats:sup>\n = 99.8%). Sensitivity analyses confirmed robustness of findings, and publication bias was not detected. Certainty of evidence was rated very low due to heterogeneity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Depression appears to be associated with an increased risk of progression from MCI to dementia; however, the very high heterogeneity and very low certainty of evidence substantially limit confidence in the magnitude and consistency of this association. These findings highlight the importance of depression screening and management in MCI populations. Integrating mental health care into cognitive disorder clinics may improve patient outcomes and potentially delay dementia onset.<\/jats:p>\n <\/jats:sec>\n \n Systematic Review registration<\/jats:title>\n identifier: CRD420261308245.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1831762","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:51:04Z","timestamp":1779339064000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Depression as a prognostic factor for conversion from mild cognitive impairment to all-cause dementia and Alzheimer's disease: a systematic review and meta-analysis of longitudinal studies"],"prefix":"10.3389","volume":"14","author":[{"given":"Madina","family":"Kassymzhanova","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Narcology, Asfendiyarov Kazakh National Medical University","place":["Almaty, Kazakhstan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuanysh","family":"Shonbay","sequence":"additional","affiliation":[{"name":"Higher School of Psychology, Turan University","place":["Almaty, Kazakhstan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga M.","family":"Shikhova","sequence":"additional","affiliation":[{"name":"Higher School of Psychology, Turan University","place":["Almaty, Kazakhstan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya","family":"Raspopova","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Narcology, Kazakh-Russian Medical University","place":["Almaty, Kazakhstan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indira","family":"Karibayeva","sequence":"additional","affiliation":[{"name":"Department of Health Policy and Community Health, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro","place":["GA, United States"]},{"name":"Department of Research Management, JSC Research Institute of Cardiology and Internal Diseases","place":["Almaty, Kazakhstan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"B1","unstructured":"1\n 80\n \n \n United\n Nations\n \n \n Ageing | United\n Nations\n \n \n World Population Prospects\n \n 2024"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1186\/s12889-025-22378-z","article-title":"Global burden of Alzheimer's disease and other dementias in adults aged 65 years and over, and health inequality related to SDI, 1990\u20132021: analysis of data from GBD 2021","volume":"25","author":"Liu","year":"2025","journal-title":"BMC Public Health"},{"key":"B3","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S1474-4422(24)00038-3","article-title":"Global, regional, and national burden of disorders affecting the nervous system, 1990\u20132021: a systematic analysis for the Global Burden of Disease Study 2021","volume":"23","author":"Steinmetz","year":"2024","journal-title":"Lancet Neurol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1038\/mp.2011.147","article-title":"The neuropathological profile of mild cognitive impairment (MCI): a systematic review","volume":"17","author":"Stephan","year":"2011","journal-title":"Mol Psychiatry"},{"key":"B5","doi-asserted-by":"publisher","first-page":"165","DOI":"10.14283\/jpad.2020.21","article-title":"Early detection of Mild Cognitive Impairment (MCI) in primary care","volume":"7","author":"Sabbagh","year":"2020","journal-title":"J Prev Alzheimers Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1080\/15622975.2019.1696473","article-title":"Management of mild cognitive impairment (MCI): the need for national and international guidelines","volume":"21","author":"Kasper","year":"2020","journal-title":"World J Biol Psychiatry"},{"key":"B7","doi-asserted-by":"publisher","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":"Mitchell","year":"2009","journal-title":"Acta Psychiatr Scand"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e12267","DOI":"10.1002\/trc2.12267","article-title":"Risk of conversion from mild cognitive impairment to dementia in low- and middle-income countries: a systematic review and meta-analysis","volume":"8","author":"McGrattan","year":"2022","journal-title":"Alzheimer's Dement"},{"key":"B9","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1212\/WNL.0b013e3181e8e8b8","article-title":"Comparing predictors of conversion and decline in mild cognitive impairment","volume":"75","author":"Landau","year":"2010","journal-title":"Neurology."},{"key":"B10","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1001\/jamapsychiatry.2016.3162","article-title":"Prevalence of depression in patients with mild cognitive impairment: a systematic review and meta-analysis","volume":"74","author":"Ismail","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"B11","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1093\/brain\/awaa405","article-title":"Depression, dementia and immune dysregulation","volume":"144","author":"Hayley","year":"2021","journal-title":"Brain."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.3390\/biomedicines13051023","article-title":"Relationship between depression and neurodegeneration: risk factor, prodrome, consequence, or something else? A scoping review","volume":"13","author":"Papa","year":"2025","journal-title":"Biomedicines."},{"key":"B13","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1186\/s12974-023-02964-x","article-title":"Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis","volume":"20","author":"Wu","year":"2023","journal-title":"J Neuroinflammation"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.31222\/osf.io\/v7gm2","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B15","doi-asserted-by":"publisher","first-page":"101484","DOI":"10.1016\/j.cegh.2023.101484","article-title":"Introduction to the GRADE tool for rating certainty in evidence and recommendations","volume":"25","author":"Prasad","year":"2024","journal-title":"Clin Epidemiol Glob Health."},{"key":"B16","unstructured":"Cochrane GRADEing Methods Group, Assessing certainty in the evidence in the context of a systematic review\n \n \n \n Sch\u00fcnemann\n HJ\n \n \n Higgins\n JPT\n \n \n Vist\n GE\n \n \n Glasziou\n P\n \n \n Akl\n EA\n \n \n Skoetz\n N\n \n \n Cochrane Handbook for Systematic Reviews of Interventions\n \n 2022"},{"key":"B17","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.jphys.2023.05.012","article-title":"Research note: interpreting findings of a systematic review using GRADE methods","volume":"69","author":"Brennan","year":"2023","journal-title":"J Physiother"},{"key":"B18","unstructured":"R\n Core Team\n \n \n A Language and Environment for Statistical Computing.\n \n 2025"},{"key":"B19","unstructured":"Posit\n team\n \n \n PBC\n RStudio: Integrated Development Environment for R, Posit Software.\n \n 2023"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e70548","DOI":"10.1002\/alz.70548","article-title":"Sex-specific association of depressive symptom trajectories with cognitive decline and clinical progression in mild cognitive impairment","volume":"21","author":"Wang","year":"2025","journal-title":"Alzheimer's Dement."},{"key":"B21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jad.2023.03.074","article-title":"Effects of race, baseline cognition, and APOE on the association of affective dysregulation with incident dementia: a longitudinal study of dementia-free older adults","volume":"332","author":"Ebrahim","year":"2023","journal-title":"J Affect Disord"},{"key":"B22","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.jagp.2018.05.002","article-title":"Depression and risk of Alzheimer dementia: a longitudinal analysis to determine predictors of increased risk among older adults with depression","volume":"26","author":"Gallagher","year":"2018","journal-title":"Am J Geriatr Psychiatry"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1001\/archneur.61.8.1290","article-title":"Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study","volume":"61","author":"Modrego","year":"2004","journal-title":"Arch Neurol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3233\/JAD-2010-1352","article-title":"Neuropsychiatric predictors of progression from amnestic-mild cognitive impairment to Alzheimer's disease: the role of depression and apathy","volume":"20","author":"Palmer","year":"2010","journal-title":"J Alzheimer's Dis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.jagp.2013.01.006","article-title":"The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease","volume":"21","author":"Rosenberg","year":"2013","journal-title":"Am J Geriatr Psychiatry."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.3233\/JAD-140405","article-title":"Depression in mild cognitive impairment is associated with progression to Alzheimer's disease: a longitudinal study","volume":"42","author":"Van Der Mussele","year":"2014","journal-title":"J Alzheimer's Dis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.jagp.2015.05.007","article-title":"Patterns of neuropsychiatric symptoms in mild cognitive impairment and risk of dementia","author":"Forrester","year":"2016","journal-title":"Am J Geriatr Psychiatry"},{"key":"B28","doi-asserted-by":"publisher","first-page":"405","DOI":"10.3233\/JAD-150603","article-title":"Impact of depressive symptoms on conversion from mild cognitive impairment subtypes to Alzheimer's disease: a community-based longitudinal study","volume":"51","author":"Kida","year":"2016","journal-title":"J Alzheimer's Dis"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.3233\/JAD-160244","article-title":"Comorbid mild cognitive impairment and depressive symptoms predict future dementia in community older adults: a 24-month follow-up longitudinal study","volume":"54","author":"Makizako","year":"2016","journal-title":"J Alzheimer's Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1177\/1533317517725812","article-title":"Self-awareness for memory impairment in amnestic mild cognitive impairment: a longitudinal study","volume":"32","author":"Cova","year":"2017","journal-title":"Am J Alzheimers Dis Other Demen"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.3233\/JAD-161135","article-title":"Severity of depression impacts imminent conversion from mild cognitive impairment to Alzheimer's disease","volume":"59","author":"Defrancesco","year":"2017","journal-title":"J Alzheimer's Dis"},{"key":"B32","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.jagp.2019.02.003","article-title":"The roles of apathy and depression in predicting Alzheimer disease: a longitudinal analysis in older adults with mild cognitive impairment","volume":"27","author":"Ruthirakuhan","year":"2019","journal-title":"Am J Geriatr Psychiatry"},{"key":"B33","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1002\/mds.27997","article-title":"et al. Prodromal dementia with lewy bodies: clinical characterization and predictors of progression","volume":"35","author":"van de Beek","year":"2020","journal-title":"Mov Disord."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.3390\/ijms24021371","article-title":"The synergic effect of AT(N) profiles and depression on the risk of conversion to dementia in patients with mild cognitive impairment","volume":"24","author":"Marqui\u00e9","year":"2023","journal-title":"Int J Mol Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"E297","DOI":"10.1212\/WNL.0000000000201386","article-title":"Estimating bidirectional transitions and identifying predictors of mild cognitive impairment","volume":"100","author":"Qin","year":"2023","journal-title":"Neurology."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e6097","DOI":"10.1002\/gps.6097","article-title":"An investigation of neuropsychiatric symptoms, contextual factors, and antidepressant treatment as risk factors for dementia development in people with mild cognitive impairment","volume":"39","author":"Willmott","year":"2024","journal-title":"Int J Geriatr Psychiatry."},{"key":"B37","doi-asserted-by":"publisher","first-page":"35418","DOI":"10.1038\/s41598-025-16620-2","article-title":"Twelve-year nationwide cohort study identifying risk factors for conversion from mild cognitive impairment to Alzheimer's disease","volume":"15","author":"Baik","year":"2025","journal-title":"Sci Rep"},{"key":"B38","doi-asserted-by":"publisher","first-page":"120066","DOI":"10.1016\/j.jad.2025.120066","article-title":"Persistent depressive-symptom trajectories predict conversion from mild cognitive impairment to Alzheimer's disease: a longitudinal ADNI study","volume":"391","author":"Ding","year":"2025","journal-title":"J Affect Disord"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e71059","DOI":"10.1002\/alz.71059","article-title":"Apathy, depression, and dementia risk in older adults: a global collaborative study","volume":"21","author":"Oh","year":"2025","journal-title":"Alzheimer's Dement"},{"key":"B40","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3389\/fphar.2020.00034","article-title":"Depressive symptoms in the elderly-an early symptom of dementia? A systematic review","volume":"11","author":"Wiels","year":"2020","journal-title":"Front Pharmacol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"16","DOI":"10.2174\/1567205017666200217104114","article-title":"Depression in dementia or dementia in depression? Systematic review of studies and hypotheses","volume":"17","author":"Brzezi\u0144ska","year":"2020","journal-title":"Curr Alzheimer Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1192\/j.eurpsy.2024.1762","article-title":"Influence of cognitive reserve on risk of depression and subsequent dementia: a large community-based longitudinal study","volume":"67","author":"Yang","year":"2024","journal-title":"Eur Psychiatry."},{"key":"B43","doi-asserted-by":"publisher","first-page":"821866","DOI":"10.3389\/fnagi.2022.821866","article-title":"Perspectives on the complex links between depression and dementia","volume":"14","author":"Hakim","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"B44","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/npp.2016.148","article-title":"Sleep health: reciprocal regulation of sleep and innate immunity","volume":"42","author":"Irwin","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet Commission, Lancet","volume":"396","author":"Livingston","year":"2020"},{"key":"B46","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1136\/bmjopen-2019-035147","article-title":"Clinical factors associated with progression to dementia in people with late-life depression: a cohort study of patients in secondary care","volume":"10","author":"Peakman","year":"2020","journal-title":"BMJ Open."},{"key":"B47","doi-asserted-by":"publisher","first-page":"103266","DOI":"10.1016\/j.eclinm.2025.103266","article-title":"Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis","volume":"84","author":"Brain","year":"2025","journal-title":"EClinicalMedicine"},{"key":"B48","doi-asserted-by":"publisher","first-page":"839","DOI":"10.3390\/medicina61050839","article-title":"Late-onset depression and dementia: a systematic review of the temporal relationships and predictive associations","volume":"61","author":"Boparai","year":"2025","journal-title":"Medicina"},{"key":"B49","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s13195-023-01308-4","article-title":"Stress, depression, and risk of dementia \u2013 a cohort study in the total population between 18 and 65 years old in Region Stockholm","volume":"15","author":"Wallensten","year":"2023","journal-title":"Alzheimers Res Ther"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e084635","DOI":"10.1002\/alz.084635","article-title":"A systematic review and meta-analysis of the association between mood disorders and Alzheimer's dementia","volume":"20","author":"Ma","year":"2025","journal-title":"Alzheimer's Dement."},{"key":"B51","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1017\/S1041610219001030","article-title":"Neuropsychiatric symptoms as predictors of conversion from MCI to dementia: a machine learning approach","volume":"32","author":"Mallo","year":"2020","journal-title":"Int Psychogeriatr"},{"key":"B52","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1159\/000357775","article-title":"The Alzheimer's disease cooperative study prevention instrument project: longitudinal outcome of behavioral measures as predictors of cognitive decline","volume":"4","author":"Banks","year":"2014","journal-title":"D"},{"key":"B53","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1007\/s40520-025-02952-6","article-title":"Specific cognitive impairment predicts the neuropsychiatric symptoms in patient with mild cognitive impairment","volume":"37","author":"Pan","year":"2025","journal-title":"Aging Clin Exp R"},{"key":"B54","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1136\/jnnp-2024-334675","article-title":"Waters, Depression and dementia: interrogating the causality of the relationship","volume":"96","author":"Paris","year":"2025","journal-title":"J Neurol Neurosurg Psychiatry"}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2026.1831762\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:51:22Z","timestamp":1779339082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2026.1831762\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":54,"alternative-id":["10.3389\/fpubh.2026.1831762"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2026.1831762","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]},"article-number":"1831762"}}