{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:02:53Z","timestamp":1789448573435,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically compare the effects of five intervention strategies centered on Cognitive Training (CT), including Routine Care (RC), CT, Physical Exercise (PE), Cognitive Plus Exercise Training (CET), and Cognitive Plus Non-Invasive Brain Stimulation (CNIBS), on cognitive function, executive function, and negative emotions in patients with Alzheimer\u2019s disease, using a network meta-analysis. The relative efficacy of different interventions was ranked to provide evidence-based support for optimizing combined treatment strategies in clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Embase, Web of Science, Cochrane Library, and EBSCO databases were systematically searched to identify randomized controlled trials on CT and its combined interventions for Alzheimer\u2019s disease published from database inception to April 2026. A network meta-analysis was conducted within a frequentist framework using Stata 17.0 software. The efficacy of interventions was ranked using the surface under the cumulative ranking curve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 19 randomized controlled trials involving more than 2,000 patients were included. The network meta-analysis showed that, for cognitive function, CNIBS (SUCRA\u202f=\u202f75.4%) and CET (SUCRA\u202f=\u202f72.4%) ranked first and second, respectively, and were significantly superior to RC and single interventions. For executive function, CET ranked highest (SUCRA\u202f=\u202f99.9%) and was significantly superior to PE alone (SMD\u202f=\u202f3.71, 95% CI: 3.16 to 4.26) and RC (SMD\u202f=\u202f1.69, 95% CI: 0.48 to 2.91), other interventions do not offer a significant advantage over RC. For negative emotions, CET ranked highest (SUCRA\u202f=\u202f83.7%), followed by PE alone (SUCRA\u202f=\u202f57.9%), and CNIBS was also superior to CT alone (SMD\u202f=\u202f1.07, 95% CI: 0.53 to 1.61).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combined interventions centered on CT are superior to single interventions in improving multidimensional symptoms in patients with Alzheimer\u2019s disease. Among them, CET shows the most prominent advantages in improving executive function and negative emotions, whereas CNIBS shows the greatest effect on overall cognitive function. In clinical practice, individualized intervention strategies should be selected according to the primary rehabilitation goal.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1883995","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:26:43Z","timestamp":1789446403000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A meta-analysis of the effects of combined interventions centered on cognitive training on cognition, executive function, and negative emotions in patients with Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Xingjun","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Leisure Services Sports, Pai Chai University","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanye","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Leisure Services Sports, Pai Chai University","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Leisure Services Sports, Pai Chai University","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1093\/procel\/pwae026","article-title":"Alzheimer's disease: insights into pathology, molecular mechanisms, and therapy","volume":"16","author":"Zheng","year":"2025","journal-title":"Protein Cell"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1016\/j.neuron.2024.01.024","article-title":"Mechanisms of sex differences in Alzheimer's disease","volume":"112","author":"Lopez-Lee","year":"2024","journal-title":"Neuron"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1002\/alz.13809","article-title":"2024 Alzheimer\u2019s disease facts and figures","volume":"20","year":"2024","journal-title":"Alzheimers Dement"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3389\/fnagi.2018.00437","article-title":"Executive functions in Alzheimer disease: a systematic review","volume":"10","author":"Guarino","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"4564","DOI":"10.3390\/nu14214564","article-title":"Diet in the prevention of Alzheimer's disease: current knowledge and future research requirements","volume":"14","author":"Stefaniak","year":"2022","journal-title":"Nutrients"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.jad.2015.09.069","article-title":"The prevalence of neuropsychiatric symptoms in Alzheimer's disease: systematic review and meta-analysis","volume":"190","author":"Zhao","year":"2016","journal-title":"J Affect Disord"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1017\/S1041610220001118","article-title":"A systematic review of the prevalence of depression, anxiety, and apathy in frontotemporal dementia, atypical and young-onset Alzheimer's disease, and inherited dementia","volume":"35","author":"Collins","year":"2023","journal-title":"Int Psychogeriatr"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.jalz.2010.04.005","article-title":"Executive function and instrumental activities of daily living in mild cognitive impairment and Alzheimer's disease","volume":"7","author":"Marshall","year":"2011","journal-title":"Alzheimers Dement"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1097\/JGP.0b013e3181d5745d","article-title":"Caregiver burden in Alzheimer disease: cross-sectional and longitudinal patient correlates","volume":"18","author":"Mohamed","year":"2010","journal-title":"Am J Geriatr Psychiatry"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1007\/s40263-025-01219-y","article-title":"Brexpiprazole for the treatment of agitation in older adults with Alzheimer's disease: a systematic review, Bayesian Meta-analysis, and Meta-regression","volume":"39","author":"da Silva","year":"2025","journal-title":"CNS Drugs"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the lancet standing commission","volume":"404","author":"Livingston","year":"2024","journal-title":"Lancet"},{"key":"ref12","year":"2018","journal-title":"Dementia: Assessment, Management and Support for People Living with Dementia and Their Carers"},{"key":"ref13","volume-title":"Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines","year":"2019"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"CD005562","DOI":"10.1002\/14651858.CD005562.pub3","article-title":"Cognitive stimulation to improve cognitive functioning in people with dementia","volume":"1","author":"Woods","year":"2023","journal-title":"Cochrane Database Syst Rev"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"CD013069","DOI":"10.1002\/14651858.CD013069.pub2","article-title":"Cognitive training for people with mild to moderate dementia","volume":"3","author":"Bahar-Fuchs","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"101479","DOI":"10.1016\/j.arr.2021.101479","article-title":"Exercise interventions in Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials","volume":"72","author":"L\u00f3pez-Ortiz","year":"2021","journal-title":"Ageing Res Rev"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"560461","DOI":"10.3389\/fpsyg.2020.560461","article-title":"Physical activity for executive function and activities of daily living in AD patients: a systematic review and Meta-analysis","volume":"11","author":"Zhu","year":"2020","journal-title":"Front Psychol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1136\/jnnp-2020-323870","article-title":"Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis","volume":"92","author":"Chu","year":"2021","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2019.08.020","article-title":"A systematic review and meta-analysis of rTMS effects on cognitive enhancement in mild cognitive impairment and Alzheimer\u2019s disease","volume":"86","author":"Chou","year":"2020","journal-title":"Neurobiol Aging"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jphys.2019.11.014","article-title":"Physical exercise attenuates cognitive decline and reduces behavioural problems in people with mild cognitive impairment and dementia: a systematic review","volume":"66","author":"Law","year":"2020","journal-title":"J Physiother"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1659208","DOI":"10.3389\/fmed.2025.1659208","article-title":"Effects of non-invasive brain stimulation combined with cognitive training on cognitive functions in older people with mild cognitive impairment: a systematic review with meta-analysis","volume":"12","author":"V\u00e1squez-Carrasco","year":"2025","journal-title":"Front Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1002\/jrsm.1037","article-title":"Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool","volume":"3","author":"Salanti","year":"2012","journal-title":"Res Synth Methods"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"ED000142","DOI":"10.1002\/14651858.ED000142","article-title":"Updated guidance for trusted systematic reviews: A new edition of the Cochrane Handbook for Systematic Reviews of Interventions","volume":"2019","author":"Cumpston","year":"2019","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.jshs.2021.05.003","article-title":"Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: a systematic review and network meta-analysis","volume":"11","author":"Huang","year":"2022","journal-title":"J Sport Health Sci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1080\/13607863.2024.2379427","article-title":"Optimal dose and type of non-pharmacological treatments to improve cognitive function in people with Alzheimer's disease: a systematic review and network meta-analysis","volume":"29","author":"Dou","year":"2025","journal-title":"Aging Ment Health"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12984-025-01566-3","article-title":"Efficacy of non-invasive brain stimulation interventions on cognitive impairment: an umbrella review of meta-analyses of randomized controlled trials","volume":"22","author":"Wu","year":"2025","journal-title":"J Neuroeng Rehabil"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.arr.2017.09.003","article-title":"Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: a meta-analysis","volume":"40","author":"Karssemeijer","year":"2017","journal-title":"Ageing Res Rev"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"591","DOI":"10.3390\/healthcare13060591","article-title":"Combined physical-cognitive therapies for the health of older adults with mild cognitive impairment: a systematic review and Meta-analysis","volume":"13","author":"Mu\u00f1oz-Perete","year":"2025","journal-title":"Healthcare"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"927128","DOI":"10.3389\/fpsyt.2022.927128","article-title":"Effect of physical exercise on cognitive function of Alzheimer's disease patients: a systematic review and Meta-analysis of randomized controlled trial","volume":"13","author":"Liu","year":"2022","journal-title":"Front Psych"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1590\/0004-282X-ANP-2020-0284","article-title":"Physical exercise is effective for neuropsychiatric symptoms in Alzheimer's disease: a systematic review","volume":"79","author":"Mendon\u00e7a","year":"2021","journal-title":"Arq Neuropsiquiatr"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1007\/s00415-019-09493-9","article-title":"Physical exercise improves quality of life, depressive symptoms, and cognition across chronic brain disorders: a transdiagnostic systematic review and meta-analysis of randomized controlled trials","volume":"268","author":"Dauwan","year":"2021","journal-title":"J Neurol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1883995\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:26:44Z","timestamp":1789446404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1883995\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":31,"alternative-id":["10.3389\/fneur.2026.1883995"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1883995","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"1883995"}}